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Cell_Biology_Alberts. Figure 1–30 Chloroplasts. These organelles capture the energy of sunlight in plant cells and some single-celled eukaryotes. (A) A single cell isolated from a leaf of a flowering plant, seen in the light microscope, showing the green chloroplasts (Movie 1.3 and see movie 14.9). (B) A drawing of one of the chloroplasts, showing the highly folded system of internal membranes containing the chlorophyll molecules by which light is absorbed. (A, courtesy of Preeti dahiya.) early eukaryotic cell eukaryotic cell capable of photosynthesis


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Cell_Biology_Alberts. Many of the genes that are missing from the mitochondria and chloroplasts have not been lost; instead, they have moved from the symbiont genome into the DNA of the host cell nucleus. The nuclear DNA of humans contains many genes coding for proteins that serve essential functions inside the mitochondria; in plants, the nuclear DNA also contains many genes specifying proteins required in chloroplasts. In both cases, the DNA sequences of these nuclear genes show clear evidence of their origin from the bacterial ancestor of the respective organelle.


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Cell_Biology_Alberts. Natural selection has evidently favored mitochondria with small genomes. By contrast, the nuclear genomes of most eukaryotes seem to have been free to enlarge. Perhaps the eukaryotic way of life has made large size an advantage: predators typically need to be bigger than their prey, and cell size generally increases in proportion to genome size. Whatever the reason, aided by a massive accumulation of DNA segments derived from parasitic transposable elements (discussed in Chapter 5), the genomes of most eukaryotes have become orders of magnitude larger than those of bacteria and archaea (Figure 1–32). The freedom to be extravagant with DNA has had profound implications. Eukaryotes not only have more genes than prokaryotes; they also have vastly more DNA that does not code for protein. The human genome contains 1000 times as many nucleotide pairs as the genome of a typical bacterium, perhaps 10 times as Figure 1–31 The origin of chloroplasts.


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Cell_Biology_Alberts. Figure 1–31 The origin of chloroplasts. An early eukaryotic cell, already possessing mitochondria, engulfed a photosynthetic bacterium (a cyanobacterium) and retained it in symbiosis. Present-day chloroplasts are thought to trace their ancestry back to a single species of cyanobacterium that was adopted as an internal symbiont (an endosymbiont) over a billion years ago. Figure 1–32 Genome sizes compared. Genome size is measured in nucleotide pairs of dnA per haploid genome, that is, per single copy of the genome. (The cells of sexually reproducing organisms such as ourselves are generally diploid: they contain two copies of the genome, one inherited from the mother, the other from the father.) closely related organisms can vary widely in the quantity of dnA in their genomes, even though they contain similar numbers of functionally distinct genes. (data from


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Cell_Biology_Alberts. W.h. li, molecular evolution, pp. 380–383. sunderland, mA: sinauer, 1997.) many genes, and a great deal more noncoding DNA (~98.5% of the genome for a human does not code for proteins, as opposed to 11% of the genome for the bacterium E. coli). The estimated genome sizes and gene numbers for some eukaryotes are compiled for easy comparison with E. coli in Table 1–2; we shall discuss how each of these eukaryotes serves as a model organism shortly.


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Cell_Biology_Alberts. Much of our noncoding DNA is almost certainly dispensable junk, retained like a mass of old papers because, when there is little pressure to keep an archive small, it is easier to retain everything than to sort out the valuable information and discard the rest. Certain exceptional eukaryotic species, such as the puffer fish, bear witness to the profligacy of their relatives; they have somehow managed to rid themselves of large quantities of noncoding DNA. Yet they appear similar in structure, behavior, and fitness to related species that have vastly more such DNA (see Figure 4–71).


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Cell_Biology_Alberts. Even in compact eukaryotic genomes such as that of puffer fish, there is more noncoding DNA than coding DNA, and at least some of the noncoding DNA certainly has important functions. In particular, it regulates the expression of adjacent genes. With this regulatory DNA, eukaryotes have evolved distinctive ways of controlling when and where a gene is brought into play. This sophisticated gene regulation is crucial for the formation of complex multicellular organisms. The Genome defines the Program of multicellular development The cells in an individual animal or plant are extraordinarily varied. Fat cells, skin cells, bone cells, nerve cells—they seem as dissimilar as any cells could be (Figure 1–33). Yet all these cell types are the descendants of a single fertilized egg cell, and all (with minor exceptions) contain identical copies of the genome of the species.


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Cell_Biology_Alberts. The differences result from the way in which the cells make selective use of their genetic instructions according to the cues they get from their surroundings in the developing embryo. The DNA is not just a shopping list specifying the molecules that every cell must have, and the cell is not an assembly of all the items on the list. Rather, the cell behaves as a multipurpose machine, with sensors to receive environmental signals and with highly developed abilities to call different sets of genes into action according to the sequences of signals to which the cell has been exposed. The genome in each cell is big enough to accommodate the Figure 1–33 Cell types can vary enormously in size and shape. An animal nerve cell is compared here with a neutrophil, a type of white blood cell. Both are drawn to scale. information that specifies an entire multicellular organism, but in any individual cell only part of that information is used.


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Cell_Biology_Alberts. information that specifies an entire multicellular organism, but in any individual cell only part of that information is used. A large number of genes in the eukaryotic genome code for proteins that regulate the activities of other genes. Most of these transcription regulators act by binding, directly or indirectly, to the regulatory DNA adjacent to the genes that are to be controlled, or by interfering with the abilities of other proteins to do so. The expanded genome of eukaryotes therefore not only specifies the hardware of the cell, but also stores the software that controls how that hardware is used (Figure 1–34).


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Cell_Biology_Alberts. Cells do not just passively receive signals; rather, they actively exchange signals with their neighbors. Thus, in a developing multicellular organism, the same control system governs each cell, but with different consequences depending on the messages exchanged. The outcome, astonishingly, is a precisely patterned array of cells in different states, each displaying a character appropriate to its position in the multicellular structure. many eukaryotes live as solitary cells


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Cell_Biology_Alberts. many eukaryotes live as solitary cells Many species of eukaryotic cells lead a solitary life—some as hunters (the protozoa), some as photosynthesizers (the unicellular algae), some as scavengers (the unicellular fungi, or yeasts). Figure 1–35 conveys something of the astonishing variety of the single-celled eukaryotes. The anatomy of protozoa, especially, is often elaborate and includes such structures as sensory bristles, photoreceptors, sinuously beating cilia, leglike appendages, mouth parts, stinging darts, and musclelike contractile bundles. Although they are single cells, protozoa can be as intricate, as versatile, and as complex in their behavior as many multicellular organisms (see Figure 1–27, Movie 1.4, and Movie 1.5).


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Cell_Biology_Alberts. In terms of their ancestry and DNA sequences, the unicellular eukaryotes are far more diverse than the multicellular animals, plants, and fungi, which arose as three comparatively late branches of the eukaryotic pedigree (see Figure 1–17). As with prokaryotes, humans have tended to neglect them because they are microscopic. Only now, with the help of genome analysis, are we beginning to understand their positions in the tree of life, and to put into context the glimpses these strange creatures can offer us of our distant evolutionary past. A yeast serves as a minimal model eukaryote The molecular and genetic complexity of eukaryotes is daunting. Even more than for prokaryotes, biologists need to concentrate their limited resources on a few selected model organisms to unravel this complexity. Figure 1–34 Genetic control of the program of multicellular development.


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Cell_Biology_Alberts. Figure 1–34 Genetic control of the program of multicellular development. The role of a regulatory gene is demonstrated in the snapdragon Antirrhinum. In this example, a mutation in a single gene coding for a regulatory protein causes leafy shoots to develop in place of flowers: because a regulatory protein has been changed, the cells adopt characters that would be appropriate to a different location in the normal plant. The mutant is on the left, the normal plant on the right. (courtesy of enrico coen and Rosemary carpenter.) To analyze the internal workings of the eukaryotic cell without the additional problems of multicellular development, it makes sense to use a species that is unicellular and as simple as possible. The popular choice for this role of minimal model eukaryote has been the yeast Saccharomyces cerevisiae (Figure 1–36)—the same species that is used by brewers of beer and bakers of bread.


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Cell_Biology_Alberts. S. cerevisiae is a small, single-celled member of the kingdom of fungi and thus, according to modern views, is at least as closely related to animals as it is to plants. It is robust and easy to grow in a simple nutrient medium. Like other fungi, it has a tough cell wall, is relatively immobile, and possesses mitochondria but not chloroplasts. When nutrients are plentiful, it grows and divides almost as rapidly as a bacterium. It can reproduce either vegetatively (that is, by simple cell division), or sexually: two yeast cells that are haploid (possessing a single copy of the genome) can fuse to create a cell that is diploid (containing a double genome); and the diploid cell can undergo meiosis (a reduction division) to produce cells that are once again haploid (Figure 1–37). In contrast with higher plants and animals, the yeast can divide indefinitely in either the haploid or the diploid state, and the process leading from one state to the other can be induced at will by changing the


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Cell_Biology_Alberts. higher plants and animals, the yeast can divide indefinitely in either the haploid or the diploid state, and the process leading from one state to the other can be induced at will by changing the growth conditions.


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Cell_Biology_Alberts. In addition to these features, the yeast has a further property that makes it a convenient organism for genetic studies: its genome, by eukaryotic standards, is exceptionally small. Nevertheless, it suffices for all the basic tasks that every eukaryotic cell must perform. Mutants are available for essentially every gene, Figure 1–35 An assortment of protozoa: a small sample of an extremely diverse class of organisms. The drawings are done to different scales, but in each case the scale bar represents 10 μm. The organisms in (A), (c), and (G) are ciliates; is a heliozoan; (d) is an amoeba; is a dinoflagellate; and (F) is a euglenoid. (From m.A. sleigh, Biology of Protozoa. cambridge, uk: cambridge university Press, 1973.)


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Cell_Biology_Alberts. Figure 1–36 The yeast Saccharomyces cerevisiae. (A) A scanning electron micrograph of a cluster of the cells. This species is also known as budding yeast; it proliferates by forming a protrusion or bud that enlarges and then separates from the rest of the original cell. many cells with buds are visible in this micrograph. (B) A transmission electron micrograph of a cross section of a yeast cell, showing its nucleus, mitochondrion, and thick cell wall. (A, courtesy of Ira herskowitz and eric schabatach.) Figure 1–37 The reproductive cycles of the yeast S. cerevisiae.


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Cell_Biology_Alberts. Figure 1–37 The reproductive cycles of the yeast S. cerevisiae. depending on environmental conditions and on details of the genotype, cells of this species can exist in either a diploid (2n) state, with a double chromosome set, or a haploid (n) state, with a single chromosome set. The diploid form can either proliferate by ordinary cell-division cycles or undergo meiosis to produce haploid cells. The haploid form can either proliferate by ordinary cell-division cycles or undergo sexual fusion with another haploid cell to become diploid. meiosis is triggered by starvation and gives rise to spores—haploid cells in a dormant state, resistant to harsh environmental conditions.


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Cell_Biology_Alberts. and studies on yeasts (using both S. cerevisiae and other species) have provided a key to many crucial processes, including the eukaryotic cell-division cycle—the critical chain of events by which the nucleus and all the other components of a cell are duplicated and parceled out to create two daughter cells from one. The control system that governs this process has been so well conserved over the course of evolution that many of its components can function interchangeably in yeast and human cells: if a mutant yeast lacking an essential yeast cell-division-cycle gene is supplied with a copy of the homologous cell-division-cycle gene from a human, the yeast is cured of its defect and becomes able to divide normally. The expression levels of All the Genes of An organism can Be monitored simultaneously


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Cell_Biology_Alberts. The expression levels of All the Genes of An organism can Be monitored simultaneously The complete genome sequence of S. cerevisiae, determined in 1997, consists of approximately 13,117,000 nucleotide pairs, including the small contribution (78,520 nucleotide pairs) of the mitochondrial DNA. This total is only about 2.5 times as much DNA as there is in E. coli, and it codes for only 1.5 times as many distinct proteins (about 6600 in all). The way of life of S. cerevisiae is similar in many ways to that of a bacterium, and it seems that this yeast has likewise been subject to selection pressures that have kept its genome compact.


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Cell_Biology_Alberts. Knowledge of the complete genome sequence of any organism—be it a yeast or a human—opens up new perspectives on the workings of the cell: things that once seemed impossibly complex now seem within our grasp. Using techniques described in Chapter 8, it is now possible, for example, to monitor, simultaneously, the amount of mRNA transcript that is produced from every gene in the yeast genome under any chosen conditions, and to see how this whole pattern of gene activity changes when conditions change. The analysis can be repeated with mRNA prepared from mutant cells lacking a chosen gene—any gene that we care to test. In principle, this approach provides a way to reveal the entire system of control relationships that govern gene expression—not only in yeast cells, but in any organism whose genome sequence is known. Arabidopsis has Been chosen out of 300,000 species As a model Plant


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Cell_Biology_Alberts. Arabidopsis has Been chosen out of 300,000 species As a model Plant The large multicellular organisms that we see around us—the flowers and trees and animals—seem fantastically varied, but they are much closer to one another in their evolutionary origins, and more similar in their basic cell biology, than the great host of microscopic single-celled organisms. Thus, while bacteria and archaea are separated by perhaps 3.5 billion years of evolution, vertebrates and insects are separated by about 700 million years, fish and mammals by about 450 million years, and the different species of flowering plants by only about 150 million years.


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Cell_Biology_Alberts. Because of the close evolutionary relationship between all flowering plants, we can, once again, get insight into the cell and molecular biology of this whole class of organisms by focusing on just one or a few species for detailed analysis. Out of the several hundred thousand species of flowering plants on Earth today, molecular biologists have chosen to concentrate their efforts on a small weed, the common Thale cress Arabidopsis thaliana (Figure 1–38), which can be grown indoors in large numbers and produces thousands of offspring per plant after 8–10 weeks. Arabidopsis has a total genome size of approximately 220 million nucleotide pairs, about 17 times the size of yeast’s (see Table 1–2). The World of Animal cells Is Represented By a Worm, a Fly, a Fish, a mouse, and a human


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Cell_Biology_Alberts. The World of Animal cells Is Represented By a Worm, a Fly, a Fish, a mouse, and a human Multicellular animals account for the majority of all named species of living organisms, and for the largest part of the biological research effort. Five species have emerged as the foremost model organisms for molecular genetic studies. In order of increasing size, they are the nematode worm Caenorhabditis elegans, the fly Drosophila melanogaster, the zebrafish Danio rerio, the mouse Mus musculus, and the human, Homo sapiens. Each has had its genome sequenced.


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Cell_Biology_Alberts. Caenorhabditis elegans (Figure 1–39) is a small, harmless relative of the eel-worm that attacks crops. With a life cycle of only a few days, an ability to survive in a freezer indefinitely in a state of suspended animation, a simple body plan, and an unusual life cycle that is well suited for genetic studies (described in Chapter 21), it is an ideal model organism. C. elegans develops with clockwork precision from a fertilized egg cell into an adult worm with exactly 959 body cells (plus a variable number of egg and sperm cells)—an unusual degree of regularity for an animal. We now have a minutely detailed description of the sequence of events by which this occurs, as the cells divide, move, and change their character according to strict and predictable rules. The genome of 130 million nucleotide pairs codes for about 21,000 proteins, and many mutants and other tools are available for the testing of gene functions. Although the worm has a body plan very different from our own, the


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Cell_Biology_Alberts. nucleotide pairs codes for about 21,000 proteins, and many mutants and other tools are available for the testing of gene functions. Although the worm has a body plan very different from our own, the conservation of biological mechanisms has been sufficient for the worm to be a model for many of the developmental and cell-biological processes that occur in the human body. Thus, for example, studies of the worm have been critical for helping us to understand the programs of cell division and cell death that determine the number of cells in the body—a topic of great importance for both developmental biology and cancer research.


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Cell_Biology_Alberts. studies in Drosophila Provide a key to vertebrate development The fruit fly Drosophila melanogaster (Figure 1–40) has been used as a model genetic organism for longer than any other; in fact, the foundations of classical genetics were built to a large extent on studies of this insect. Over 80 years ago, it provided, for example, definitive proof that genes—the abstract units of hereditary information—are carried on chromosomes, concrete physical objects whose behavior had been closely followed in the eukaryotic cell with the light microscope, but whose function was at first unknown. The proof depended on one of the many features that make Drosophila peculiarly convenient for genetics—the giant chromosomes, with characteristic banded appearance, that are visible in Figure 1–38 Arabidopsis thaliana, the plant chosen as the primary model for studying plant molecular genetics. (courtesy of Toni hayden and the John Innes Foundation.) 0.2 mm


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Cell_Biology_Alberts. Figure 1–38 Arabidopsis thaliana, the plant chosen as the primary model for studying plant molecular genetics. (courtesy of Toni hayden and the John Innes Foundation.) 0.2 mm Figure 1–39 Caenorhabditis elegans, the first multicellular organism to have its complete genome sequence determined. This small nematode, about 1 mm long, lives in the soil. most individuals are hermaphrodites, producing both eggs and sperm. (courtesy of maria Gallegos, university of Wisconsin, madison.) some of its cells (Figure 1–41). Specific changes in the hereditary information, manifest in families of mutant flies, were found to correlate exactly with the loss or alteration of specific giant-chromosome bands.


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Cell_Biology_Alberts. In more recent times, Drosophila, more than any other organism, has shown us how to trace the chain of cause and effect from the genetic instructions encoded in the chromosomal DNA to the structure of the adult multicellular body. Drosophila mutants with body parts strangely misplaced or mispatterned provided the key to the identification and characterization of the genes required to make a properly structured body, with gut, limbs, eyes, and all the other parts in their correct places. Once these Drosophila genes were sequenced, the genomes of vertebrates could be scanned for homologs. These were found, and their functions in vertebrates were then tested by analyzing mice in which the genes had been mutated. The results, as we see later in the book, reveal an astonishing degree of similarity in the molecular mechanisms that govern insect and vertebrate development (discussed in Chapter 21).


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Cell_Biology_Alberts. The majority of all named species of living organisms are insects. Even if Drosophila had nothing in common with vertebrates, but only with insects, it would still be an important model organism. But if understanding the molecular genetics of vertebrates is the goal, why not simply tackle the problem head-on? Why sidle up to it obliquely, through studies in Drosophila?


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Cell_Biology_Alberts. Drosophila requires only 9 days to progress from a fertilized egg to an adult; it is vastly easier and cheaper to breed than any vertebrate, and its genome is much smaller—about 200 million nucleotide pairs, compared with 3200 million for a human. This genome codes for about 15,000 proteins, and mutants can now be obtained for essentially any gene. But there is also another, deeper reason why genetic mechanisms that are hard to discover in a vertebrate are often readily revealed in the fly. This relates, as we now explain, to the frequency of gene duplication, which is substantially greater in vertebrate genomes than in the fly genome and has probably been crucial in making vertebrates the complex and subtle creatures that they are. The vertebrate Genome Is a Product of Repeated duplications


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Cell_Biology_Alberts. The vertebrate Genome Is a Product of Repeated duplications Almost every gene in the vertebrate genome has paralogs—other genes in the same genome that are unmistakably related and must have arisen by gene duplication. In many cases, a whole cluster of genes is closely related to similar clusters present elsewhere in the genome, suggesting that genes have been duplicated in linked groups rather than as isolated individuals. According to one hypothesis, at an early stage in the evolution of the vertebrates, the entire genome underwent duplication twice in succession, giving rise to four copies of every gene. The precise course of vertebrate genome evolution remains uncertain, because many further evolutionary changes have occurred since these ancient events. Figure 1–40 Drosophila melanogaster.


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Cell_Biology_Alberts. The precise course of vertebrate genome evolution remains uncertain, because many further evolutionary changes have occurred since these ancient events. Figure 1–40 Drosophila melanogaster. molecular genetic studies on this fly have provided the main key to understanding how all animals develop from a fertilized egg into an adult. (From e.B. lewis, Science 221:cover, 1983. With permission from AAAs.) Figure 1–41 Giant chromosomes from salivary gland cells of Drosophila.


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Cell_Biology_Alberts. Figure 1–41 Giant chromosomes from salivary gland cells of Drosophila. Because many rounds of dnA replication have occurred without an intervening cell division, each of the chromosomes in these unusual cells contains over 1000 identical dnA molecules, all aligned in register. This makes them easy to see in the light microscope, where they display a characteristic and reproducible banding pattern. specific bands can be identified as the locations of specific genes: a mutant fly with a region of the banding pattern missing shows a phenotype reflecting loss of the genes in that region. Genes that are being transcribed at a high rate correspond to bands with a “puffed” appearance. The bands stained dark brown in the micrograph are sites where a particular regulatory protein is bound to the dnA. (courtesy of B. Zink and R. Paro, from R. Paro, Trends Genet. 6:416–421, 1990. With permission from elsevier.)


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Cell_Biology_Alberts. R. Paro, Trends Genet. 6:416–421, 1990. With permission from elsevier.) Genes that were once identical have diverged; many of the gene copies have been lost through disruptive mutations; some have undergone further rounds of local duplication; and the genome, in each branch of the vertebrate family tree, has suffered repeated rearrangements, breaking up most of the original gene orderings. Comparison of the gene order in two related organisms, such as the human and the mouse, reveals that—on the time scale of vertebrate evolution—chromosomes frequently fuse and fragment to move large blocks of DNA sequence around. Indeed, it is possible, as discussed in Chapter 4, that the present state of affairs is the result of many separate duplications of fragments of the genome, rather than duplications of the genome as a whole.


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Cell_Biology_Alberts. There is, however, no doubt that such whole-genome duplications do occur from time to time in evolution, for we can see recent instances in which duplicated chromosome sets are still clearly identifiable as such. The frog genus Xenopus, for example, comprises a set of closely similar species related to one another by repeated duplications or triplications of the whole genome. Among these frogs are X. tropicalis, with an ordinary diploid genome; the common laboratory species X. laevis, with a duplicated genome and twice as much DNA per cell; and X. ruwenzoriensis, with a sixfold reduplication of the original genome and six times as much DNA per cell (108 chromosomes, compared with 36 in X. laevis, for example). These species are estimated to have diverged from one another within the past 120 million years (Figure 1–42). The Frog and the Zebrafish Provide Accessible models for vertebrate development


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Cell_Biology_Alberts. The Frog and the Zebrafish Provide Accessible models for vertebrate development Frogs have long been used to study the early steps of embryonic development in vertebrates, because their eggs are big, easy to manipulate, and fertilized outside of the animal, so that the subsequent development of the early embryo is easily followed (Figure 1–43). Xenopus laevis, in particular, continues to be an important model organism, even though it is poorly suited for genetic analysis (Movie 1.6 and see Movie 21.1).


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Cell_Biology_Alberts. The zebrafish Danio rerio has similar advantages, but without this drawback. Its genome is compact—only half as big as that of a mouse or a human—and it has a generation time of only about three months. Many mutants are known, and genetic engineering is relatively easy. The zebrafish has the added virtue that it is transparent for the first two weeks of its life, so that one can watch the behavior of individual cells in the living organism (see Movie 21.2). All this has made it an increasingly important model vertebrate (Figure 1–44). The mouse Is the Predominant mammalian model organism


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Cell_Biology_Alberts. The mouse Is the Predominant mammalian model organism Mammals have typically two times as many genes as Drosophila, a genome that is 16 times larger, and millions or billions of times as many cells in their adult bodies. In terms of genome size and function, cell biology, and molecular mechanisms, mammals are nevertheless a highly uniform group of organisms. Even anatomically, the differences among mammals are chiefly a matter of size and proportions; it is hard to think of a human body part that does not have a counterpart in elephants and mice, and vice versa. Evolution plays freely with quantitative features, but it does not readily change the logic of the structure.


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Cell_Biology_Alberts. Figure 1–42 Two species of the frog genus Xenopus. X. tropicalis, above, has an ordinary diploid genome; X. laevis, below, has twice as much dnA per cell. From the banding patterns of their chromosomes and the arrangement of genes along them, as well as from comparisons of gene sequences, it is clear that the large-genome species have evolved through duplications of the whole genome. These duplications are thought to have occurred in the aftermath of matings between frogs of slightly divergent Xenopus species. (courtesy of e. Amaya, m. offield, and R. Grainger, Trends Genet. 14:253– 255, 1998. With permission from elsevier.) Figure 1–43 Stages in the normal development of a frog. These drawings show the development of a Rana pipiens tadpole from a fertilized egg. The entire process takes place outside of the mother, making the mechanisms tail bud involved readily accessible for experimental studies. (From W. shumway, Anat. Rec. 78:139–147, 1940.)


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Cell_Biology_Alberts. For a more exact measure of how closely mammalian species resemble one another genetically, we can compare the nucleotide sequences of corresponding (orthologous) genes, or the amino acid sequences of the proteins that these genes encode. The results for individual genes and proteins vary widely. But typically, if we line up the amino acid sequence of a human protein with that of the orthologous protein from, say, an elephant, about 85% of the amino acids are identical. A similar comparison between human and bird shows an amino acid identity of about 70%—twice as many differences, because the bird and the mammalian lineages have had twice as long to diverge as those of the elephant and the human (Figure 1–45).


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Cell_Biology_Alberts. The mouse, being small, hardy, and a rapid breeder, has become the foremost model organism for experimental studies of vertebrate molecular genetics. Many naturally occurring mutations are known, often mimicking the effects of corresponding mutations in humans (Figure 1–46). Methods have been developed, moreover, to test the function of any chosen mouse gene, or of any noncoding portion of the mouse genome, by artificially creating mutations in it, as we explain later in the book. Just one made-to-order mutant mouse can provide a wealth of information for the cell biologist. It reveals the effects of the chosen mutation in a host of different contexts, simultaneously testing the action of the gene in all the different kinds of cells in the body that could in principle be affected. As humans, we have a special interest in the human genome. We want to know the full set of parts from which we are made, and to discover how they work. But even


Cell_Biology_Alberts

Cell_Biology_Alberts. As humans, we have a special interest in the human genome. We want to know the full set of parts from which we are made, and to discover how they work. But even Figure 1–44 Zebrafish as a model for studies of vertebrate development. These small, hardy tropical fish are convenient for genetic studies. Additionally, they have transparent embryos that develop outside of the mother, so that one can clearly observe cells moving and changing their character in the living organism throughout its development. (A) Adult fish. (B) An embryo 24 hours after fertilization. (A, with permission from steve Baskauf; B, from m. Rhinn et al., Neural Dev. 4:12, 2009.)


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Cell_Biology_Alberts. Figure 1–45 Times of divergence of different vertebrates. The scale on the left shows the estimated date and geological era of the last common ancestor of each specified pair of animals. each time estimate is based on comparisons of the amino acid sequences of orthologous proteins; the longer the animals of a pair have had to evolve independently, the smaller the percentage of amino acids that remain identical. The time scale has been calibrated to match the fossil evidence showing that the last common ancestor of mammals and birds lived 310 million years ago.


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Cell_Biology_Alberts. The figures on the right give data on protein—the α chain of hemoglobin. note that although there is a clear general trend of increasing divergence with increasing time for this protein, there are irregularities that are thought to reflect the action of changes of hemoglobin sequence when the organisms experienced special physiological demands. some proteins, subject to stricter functional constraints, evolve much more slowly than hemoglobin, time in millions of years others as much as five times faster. All this gives rise to substantial uncertainties in estimates of divergence times, and some experts believe that the major groups of mammals diverged from one another as if you were a mouse, preoccupied with the molecular biology of mice, humans would be attractive as model genetic organisms, because of one special property: through medical examinations and self-reporting, we catalog our own genetic (and other) disorders. The human population is enormous, consisting today of some 7


Cell_Biology_Alberts

Cell_Biology_Alberts. because of one special property: through medical examinations and self-reporting, we catalog our own genetic (and other) disorders. The human population is enormous, consisting today of some 7 billion individuals, and this self-documenting property means that a huge database of information exists on human mutations. The human genome sequence of more than 3 billion nucleotide pairs has been determined for thousands of different people, making it easier than ever before to identify at a molecular level the precise genetic change responsible for any given human mutant phenotype.


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Cell_Biology_Alberts. By drawing together the insights from humans, mice, fish, flies, worms, yeasts, plants, and bacteria—using gene sequence similarities to map out the correspondences between one model organism and another—we are enriching our understanding of them all. much as 60 million years more recently than shown here. (Adapted from s. kumar and s.B. hedges, Nature 392:917–920, 1998. With permission from macmillan Publishers ltd.) Figure 1–46 Human and mouse: similar genes and similar development. The human baby and the mouse shown here have similar white patches on their foreheads because both have mutations in the same gene (called Kit), required for the development and maintenance of pigment cells. (courtesy of R.A. Fleischman.)


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Cell_Biology_Alberts. What precisely do we mean when we speak of the human genome? Whose genome? On average, any two people taken at random differ in about one or two in every 1000 nucleotide pairs in their DNA sequence. The genome of the human species is, properly speaking, a very complex thing, embracing the entire pool of variant genes found in the human population. Knowledge of this variation is helping us to understand, for example, why some people are prone to one disease, others to another; why some respond well to a drug, others badly. It is also providing clues to our history—the population movements and minglings of our ancestors, the infections they suffered, the diets they ate. All these things have left traces in the variant forms of genes that survive today in the human communities that populate the globe. To understand cells and organisms Will Require mathematics, computers, and Quantitative Information


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Cell_Biology_Alberts. To understand cells and organisms Will Require mathematics, computers, and Quantitative Information Empowered by knowledge of complete genome sequences, we can list the genes, proteins, and RNA molecules in a cell, and we have methods that allow us to begin to depict the complex web of interactions between them. But how are we to turn all this information into an understanding of how cells work? Even for a single cell type belonging to a single species of organism, the current deluge of data seems overwhelming. The sort of informal reasoning on which biologists usually rely seems totally inadequate in the face of such complexity.


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Cell_Biology_Alberts. In fact, the difficulty is more than just a matter of information overload. Biological systems are, for example, full of feedback loops, and the behavior of even the simplest of systems with feedback is remarkably difficult to predict by intuition alone (Figure 1–47); small changes in parameters can cause radical changes in outcome. To go from a circuit diagram to a prediction of the behavior of the system, we need detailed quantitative information, and to draw deductions from that information we need mathematics and computers.


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Cell_Biology_Alberts. Such tools for quantitative reasoning are essential, but they are not all-powerful. You might think that, knowing how each protein influences each other protein, and how the expression of each gene is regulated by the products of others, we should soon be able to calculate how the cell as a whole will behave, just as an astronomer can calculate the orbits of the planets, or a chemical engineer can calculate the flows through a chemical plant. But any attempt to perform this feat for anything close to an entire living cell rapidly reveals the limits of our present knowledge. The information we have, plentiful as it is, is full of gaps and uncertainties. Moreover, it is largely qualitative rather than quantitative. Most often, cell biologists studying the cell’s control systems sum up their knowledge in simple schematic diagrams—this book is full of them—rather than in numbers, graphs, and differential equations.


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Cell_Biology_Alberts. To progress from qualitative descriptions and intuitive reasoning to quantitative descriptions and mathematical deduction is one of the biggest challenges for contemporary cell biology. So far, the challenge has been met only for a few very simple fragments of the machinery of living cells—subsystems involving a handful of different proteins, or two or three cross-regulatory genes, where theory and experiment go closely hand in hand. We discuss some of these examples later in the book and devote the entire final section of Chapter 8 to the role of quantitation in cell biology.


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Cell_Biology_Alberts. Knowledge and understanding bring the power to intervene—with humans, to avoid or prevent disease; with plants, to create better crops; with bacteria, to turn them to our own uses. All these biological enterprises are linked, because the genetic information of all living organisms is written in the same language. The new-found ability of molecular biologists to read and decipher this language has already begun to transform our relationship to the living world. The account of cell biology in the subsequent chapters will, we hope, equip the reader to understand, and possibly to contribute to, the great scientific adventure of the twenty-first century.


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Cell_Biology_Alberts. Figure 1–47 A very simple regulatory circuit—a single gene regulating its own expression by the binding of its protein product to its own regulatory DNA. simple schematic diagrams such as this are found throughout this book. They are often used to summarize what we know, but they leave many questions unanswered. When the protein binds, does it inhibit or stimulate transcription from the gene? how steeply does the transcription rate depend on the protein concentration? how long, on average, does a molecule of the protein remain bound to the dnA? how long does it take to make each molecule of mRnA or protein, and how quickly does each type of molecule get degraded? As explained in chapter 8, mathematical modeling shows that we need quantitative answers to all these and other questions before we can predict the behavior of even this single-gene system. For different parameter values, the system may settle to a unique steady state; or it may behave as a switch, capable of existing in one


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Cell_Biology_Alberts. we can predict the behavior of even this single-gene system. For different parameter values, the system may settle to a unique steady state; or it may behave as a switch, capable of existing in one or another of a set of alternative states; or it may oscillate; or it may show large random fluctuations.


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Cell_Biology_Alberts. Eukaryotic cells, by definition, keep their DNA in a separate membrane-enclosed compartment, the nucleus. They have, in addition, a cytoskeleton for support and movement, elaborate intracellular compartments for digestion and secretion, the capacity (in many species) to engulf other cells, and a metabolism that depends on the oxidation of organic molecules by mitochondria. These properties suggest that eukaryotes may have originated as predators on other cells. Mitochondria—and, in plants, chloroplasts—contain their own genetic material, and they evidently evolved from bacteria that were taken up into the cytoplasm of ancient cells and survived as symbionts.


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Cell_Biology_Alberts. Eukaryotic cells typically have 3–30 times as many genes as prokaryotes, and often thousands of times more noncoding DNA. The noncoding DNA allows for great complexity in the regulation of gene expression, as required for the construction of complex multicellular organisms. Many eukaryotes are, however, unicellular—among them the yeast Saccharomyces cerevisiae, which serves as a simple model organism for eukaryotic cell biology, revealing the molecular basis of many fundamental processes that have been strikingly conserved during a billion years of evolution. A small number of other organisms have also been chosen for intensive study: a worm, a fly, a fish, and the mouse serve as “model organisms” for multicellular animals; and a small milkweed serves as a model for plants.


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Cell_Biology_Alberts. Powerful new technologies such as genome sequencing are producing striking advances in our knowledge of human beings, and they are helping to advance our understanding of human health and disease. But living systems are incredibly complex, and mammalian genomes contain multiple closely related homologs of most genes. This genetic redundancy has allowed diversification and specialization of genes for new purposes, but it also makes biological mechanisms harder to decipher. For this reason, simpler model organisms have played a key part in revealing universal genetic mechanisms of animal development, and research using these systems remains critical for driving scientific and medical advances. Which statements are true? explain why or why not.


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Cell_Biology_Alberts. Which statements are true? explain why or why not. What new approaches might provide a clearer view of the anaerobic archaeon that is thought to have formed the nucleus of the first eukaryotic cell? how did its symbiosis with an aerobic bacterium lead to the mitochondrion? somewhere on earth, are there cells not yet identified that can fill in the details of how eukaryotic cells originated? dnA sequencing has revealed a rich and previously undiscovered world of microbial cells, the vast majority of which fail to grow in a laboratory. how might these cells be made more accessible for detailed study? What new model cells or organisms should be developed for scientists to study? Why might a concerted focus on these models speed progress toward understanding a critical aspect of cell function that is poorly understood? how did the first cell membranes arise?


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Cell_Biology_Alberts. how did the first cell membranes arise? 1–1 Each member of the human hemoglobin gene illustrated in Figure Q1–1. Only one in a million computfamily, which consists of seven genes arranged in two clus-er-generated “random” codes is more error-resistant than ters on different chromosomes, is an ortholog to all of the the natural genetic code. Does the extraordinary mutation other members. resistance of the genetic code argue in favor of its origin as a frozen accident or as a result of natural selection? Explain 1–2 Horizontal gene transfer is more prevalent in sin- your reasoning. gle-celled organisms than in multicellular organisms. 1–3 Most of the DNA sequences in a bacterial genome code for proteins, whereas most of the DNA sequences in the human genome do not. Discuss the following problems.


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Cell_Biology_Alberts. 1–3 Most of the DNA sequences in a bacterial genome code for proteins, whereas most of the DNA sequences in the human genome do not. Discuss the following problems. 1–4 Since it was deciphered four decades ago, some have claimed that the genetic code must be a frozen acci number of codes (thousands) dent, while others have argued that it was shaped by nat susceptibility to mutation ural selection. A striking feature of the genetic code is its inherent resistance to the effects of mutation. For example, Figure Q1–1 susceptibility to mutation of the natural code shown a change in the third position of a codon often specifies the relative to that of millions of computer-generated alternative genetic codes (Problem 1–4). susceptibility measures the average change in same amino acid or one with similar chemical properties. amino acid properties caused by random mutations in a genetic code. The natural code resists mutation more effectively (is less


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Cell_Biology_Alberts. amino acid properties caused by random mutations in a genetic code. The natural code resists mutation more effectively (is less A small value indicates that mutations tend to cause minor changes.susceptible to error) than most other possible versions, as (data courtesy of steve Freeland.) 1–5 You have begun to characterize a sample obtained from the depths of the oceans on Europa, one of Jupiter’s moons. Much to your surprise, the sample contains a life-form that grows well in a rich broth. Your preliminary analysis shows that it is cellular and contains DNA, RNA, and protein. When you show your results to a colleague, she suggests that your sample was contaminated with an organism from Earth. What approaches might you try to distinguish between contamination and a novel cellular life-form based on DNA, RNA, and protein?


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Cell_Biology_Alberts. 1–6 It is not so difficult to imagine what it means to feed on the organic molecules that living things produce. That is, after all, what we do. But what does it mean to “feed” on sunlight, as phototrophs do? Or, even stranger, to “feed” on rocks, as lithotrophs do? Where is the “food,” for example, in the mixture of chemicals (H2S, H2, CO, Mn+, Fe2+, Ni2+, CH4, and NH4+) that spews from a hydrothermal vent? 1–7 How many possible different trees (branching patterns) can in theory be drawn to display the evolution of bacteria, archaea, and eukaryotes, assuming that they all arose from a common ancestor? 1–8 The genes for ribosomal RNA are highly conserved (relatively few sequence changes) in all organisms on Earth; thus, they have evolved very slowly over time. Were ribosomal RNA genes “born” perfect?


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Cell_Biology_Alberts. 1–9 Genes participating in informational processes such as replication, transcription, and translation are transferred between species much less often than are genes involved in metabolism. The basis for this inequality is unclear at present, but one suggestion is that it relates to the underlying complexity of the two types of processes. Informational processes tend to involve large aggregates of different gene products, whereas metabolic reactions are usually catalyzed by enzymes composed of a single protein. Why would the complexity of the underlying process—informational or metabolic—have any effect on the rate of horizontal gene transfer?


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Cell_Biology_Alberts. 1–10 Animal cells have neither cell walls nor chloroplasts, whereas plant cells have both. Fungal cells are somewhere in between; they have cell walls but lack chloroplasts. Are fungal cells more likely to be animal cells that gained the ability to make cell walls, or plant cells that lost their chloroplasts? This question represented a difficult issue for early investigators who sought to assign evolutionary relationships based solely on cell characteristics and morphology. How do you suppose that this question was eventually decided?


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Cell_Biology_Alberts. Figure Q1–2 Phylogenetic tree for hemoglobin genes from a variety of species (Problem 1–11). The legumes are highlighted in green. The lengths of lines that connect the present-day species represent the evolutionary distances that separate them. Barley ChlamydomonasParameciumNematode Clam Insect Earthworm Goldfsh Frog Salamander Cobra Chicken Rabbit Whale Cat Human Cow LotusAlfalfaBeanVERTEBRATES INVERTEBRATES PROTOZOA PLANTS 1–11 When plant hemoglobin genes were first discovered in legumes, it was so surprising to find a gene typical of animal blood that it was hypothesized that the plant gene arose by horizontal transfer from an animal. Many more hemoglobin genes have now been sequenced, and a phylogenetic tree based on some of these sequences is shown in Figure Q1–2. A. Does this tree support or refute the hypothesis that the plant hemoglobins arose by horizontal gene transfer?


Cell_Biology_Alberts

Cell_Biology_Alberts. A. Does this tree support or refute the hypothesis that the plant hemoglobins arose by horizontal gene transfer? b. Supposing that the plant hemoglobin genes were originally derived from a parasitic nematode, for example, what would you expect the phylogenetic tree to look like? 1–12 Rates of evolution appear to vary in different lineages. For example, the rate of evolution in the rat lineage is significantly higher than in the human lineage. These rate differences are apparent whether one looks at changes in nucleotide sequences that encode proteins and are subject to selective pressure or at changes in noncoding nucleotide sequences, which are not under obvious selection pressure. Can you offer one or more possible explanations for the slower rate of evolutionary change in the human lineage versus the rat lineage? Alberts B, Bray d, hopkin k et al. (2014) essential cell Biology, 4th ed. new york: Garland science.


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Cell_Biology_Alberts. Alberts B, Bray d, hopkin k et al. (2014) essential cell Biology, 4th ed. new york: Garland science. Barton nh, Briggs deG, eisen JA et al. (2007) evolution. cold spring harbor, ny: cold spring harbor laboratory Press. darwin c (1859) on the origin of species. london: murray. Graur d & li W-h (1999) Fundamentals of molecular evolution, 2nd ed. sunderland, mA: sinauer Associates. madigan mT, martinko Jm, stahl d et al. (2010) Brock Biology of microorganisms, 13th ed. menlo Park, cA: Benjamin-cummings. margulis l & chapman mJ (2009) kingdoms and domains: An Illustrated Guide to the Phyla of life on earth, 1st ed. san diego: Academic Press. moore JA (1993) science As a Way of knowing. cambridge, mA: harvard university Press. moore JA (1972) heredity and development, 2nd ed. new york: oxford university Press. (Free download at www.nap.edu) yang Z (2014) molecular evolution: A statistical Approach. oxford: oxford university Press. The Universal Features of Cells On earth


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Cell_Biology_Alberts. The Universal Features of Cells On earth Andersson sGe (2006) The bacterial world gets smaller. Science 314, 259–260. Brenner s, Jacob F & meselson m (1961) An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 190, 576–581. deamer d & szostak JW eds. (2010) The origins of life (cold spring harbor Perspectives in Biology). ny: cold spring harbor laboratory Press. Gibson dG, Benders GA, Andrews-Pfannkoch c et al. (2008) complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 319, 1215–1220. Glass JI, Assad-Garcia n, Alperovich n et al. (2006) essential genes of a minimal bacterium. Proc. Natl Acad. Sci. USA 103, 425–430. harris Jk, kelley sT, spiegelman GB et al. (2003) The genetic core of the universal ancestor. Genome Res. 13, 407–413. koonin ev (2005) orthologs, paralogs, and evolutionary genomics. Annu. Rev. Genet. 39, 309–338.


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Cell_Biology_Alberts. koonin ev (2005) orthologs, paralogs, and evolutionary genomics. Annu. Rev. Genet. 39, 309–338. noller h (2005) RnA structure: reading the ribosome. Science 309, 1508–1514. Rinke c, schwientek P, sczyrba A et al. (2013) Insights into the phylogeny and coding potential of microbial dark matter. Nature 499, 431–437. Watson Jd & crick Fhc (1953) molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 171, 737–738. The Diversity of Genomes and the Tree of Life Blattner FR, Plunkett G, Bloch cA et al. (1997) The complete genome sequence of Escherichia coli k-12. Science 277, 1453–1474. Boucher y, douady cJ, Papke RT et al. (2003) lateral gene transfer and the origins of prokaryotic groups. Annu. Rev. Genet. 37, 283–328. cavicchioli R (2010) Archaea–timeline of the third domain. Nat. Rev. Microbiol. 9, 51–61.


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Cell_Biology_Alberts. cavicchioli R (2010) Archaea–timeline of the third domain. Nat. Rev. Microbiol. 9, 51–61. choudhuri s (2014) Bioinformatics for Beginners: Genes, Genomes, molecular evolution, databases and Analytical Tools, 1st ed. san diego: Academic Press. dixon B (1997) Power unseen: how microbes Rule the World. oxford:oxford university Press. handelsman J (2004) metagenomics: applications of genomics to uncultured microorganisms. Microbiol. Mol. Biol. Rev. 68, 669–685. kerr RA (1997) life goes to extremes in the deep earth—and elsewhere? Science 276, 703–704. lee TI, Rinaldi nJ, Robert F et al. (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804. olsen GJ & Woese cR (1997) Archaeal genomics: an overview. Cell 89:991–994. Williams TA, Foster PG, cox cJ & embley Tm (2013) An archaeal origin of eukaryotes supports only two primary domains of life. Nature 504, 231–235. Woese c (1998) The universal ancestor. Proc. Natl Acad. Sci. USA 95, 6854–6859.


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Cell_Biology_Alberts. Woese c (1998) The universal ancestor. Proc. Natl Acad. Sci. USA 95, 6854–6859. Adams md, celniker se, holt RA et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 2185–2195. Amborella Genome Project (2013) The Amborella genome and the evolution of flowering plants. Science 342, 1241089. Andersson sG, Zomorodipour A, Andersson Jo et al. (1998) The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140. The Arabidopsis Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815. carroll sB, Grenier Jk & Weatherbee sd (2005) From dnA to diversity: molecular Genetics and the evolution of Animal design, 2nd ed. maldon, mA: Blackwell science. de duve c (2007) The origin of eukaryotes: a reappraisal. Nat. Rev. Genet. 8, 395–403. delsuc F, Brinkmann h & Philippe h (2005) Phylogenomics and the reconstruction of the tree of life. Nat. Rev. Genet. 6, 361–375.


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Cell_Biology_Alberts. delsuc F, Brinkmann h & Philippe h (2005) Phylogenomics and the reconstruction of the tree of life. Nat. Rev. Genet. 6, 361–375. deRisi Jl, Iyer vR & Brown Po (1997) exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680–686. Gabriel sB, schaffner sF, nguyen h et al. (2002) The structure of haplotype blocks in the human genome. Science 296, 2225–2229. Goffeau A, Barrell BG, Bussey h et al. (1996) life with 6000 genes. Science 274, 546–567. International human Genome sequencing consortium (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921. keeling PJ & koonin ev eds. (2014) The origin and evolution of eukaryotes (cold spring harbor Perspectives in Biology). ny: cold spring harbor laboratory Press. lander es (2011) Initial impact of the sequencing of the human genome. Nature 470, 187–197. lynch m & conery Js (2000) The evolutionary fate and consequences of duplicate genes. Science 290, 1151–1155.


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Cell_Biology_Alberts. lynch m & conery Js (2000) The evolutionary fate and consequences of duplicate genes. Science 290, 1151–1155. national center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/ owens k & king mc (1999) Genomic views of human history. Science 286, 451–453. Palmer Jd & delwiche cF (1996) second-hand chloroplasts and the case of the disappearing nucleus. Proc. Natl Acad. Sci. USA 93, 7432–7435. Reed FA & Tishkoff sA (2006) African human diversity, origins and migrations. Curr. Opin. Genet. Dev. 16, 597–605. Rine J (2014) A future of the model organism model. Mol. Biol. Cell 25, 549–553. Rubin Gm, yandell md, Wortman JR et al. (2000) comparative genomics of the eukaryotes. Science 287, 2204–2215. shen y, yue F, mccleary d et al. (2012) A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116–120. The C. elegans sequencing consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018.


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Cell_Biology_Alberts. The C. elegans sequencing consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018. Tinsley Rc & kobel hR eds. (1996) The Biology of Xenopus. oxford: clarendon Press. Tyson JJ, chen kc & novak B (2003) sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr. Opin. Cell Biol. 15, 221–231. venter Jc, Adams md, myers eW et al (2001) The sequence of the human genome. Science 291, 1304–1351. It is at first sight difficult to accept the idea that living creatures are merely chemical systems. Their incredible diversity of form, their seemingly purposeful behavior, and their ability to grow and reproduce all seem to set them apart from the world of solids, liquids, and gases that chemistry normally describes. Indeed, until the nineteenth century animals were believed to contain a Vital Force—an “animus”—that was responsible for their distinctive properties.


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Cell_Biology_Alberts. We now know that there is nothing in living organisms that disobeys chemical or physical laws. However, the chemistry of life is indeed special. First, it is based overwhelmingly on carbon compounds, the study of which is known as organic chemistry. Second, cells are 70% water, and life depends largely on chemical reactions that take place in aqueous solution. Third, and most important, cell chemistry is enormously complex: even the simplest cell is vastly more complicated in its chemistry than any other chemical system known. In particular, although cells contain a variety of small carbon-containing molecules, most of the carbon atoms present are incorporated into enormous polymeric molecules—chains of chemical subunits linked end-to-end. It is the unique properties of these macromolecules that enable cells and organisms to grow and reproduce—as well as to do all the other things that are characteristic of life. The ChemiCal ComponenTs of a Cell


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Cell_Biology_Alberts. The ChemiCal ComponenTs of a Cell Living organisms are made of only a small selection of the 92 naturally occurring elements, four of which—carbon (C), hydrogen (H), nitrogen (N), and oxygen (O)—make up 96.5% of an organism’s weight (Figure 2–1). The atoms of these elements are linked together by covalent bonds to form molecules (see Panel 2–1, pp. 90–91). Because covalent bonds are typically 100 times stronger than the thermal energies within a cell, they resist being pulled apart by thermal motions, and they are normally broken only during specific chemical reactions with other atoms and molecules. Two different molecules can be held together by noncovalent bonds, The ChemiCal ComponenTs of a Cell CaTalYsis anD The Use of eneRGY BY Cells


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Cell_Biology_Alberts. The ChemiCal ComponenTs of a Cell CaTalYsis anD The Use of eneRGY BY Cells Figure 2–1 The main elements in cells, highlighted in the periodic table. When ordered by their atomic number and arranged in this manner, elements fall into vertical columns that show similar properties. atoms in the same vertical column must gain (or lose) the same number of electrons to attain a filled outer shell, and they thus behave similarly in bond or ion formation. Thus, for example, mg and Ca tend to give away the two electrons in their outer shells. C, n, and o occur in the same horizontal row, and tend to complete their second shells by sharing electrons.


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Cell_Biology_Alberts. The four elements highlighted in red constitute 99% of the total number of atoms present in the human body. an additional seven elements, highlighted in blue, together represent about 0.9% of the total. The elements shown in green are required in trace amounts by humans. it remains unclear whether those elements shown in yellow are essential in humans. The chemistry of life, it seems, is therefore predominantly the chemistry of lighter elements. The atomic weights shown here are those of the most common isotope of each element. 1000 10,000 kJ which are much weaker (Figure 2–2). We shall see later that noncovalent bonds are important in the many situations where molecules have to associate and dissociate readily to carry out their biological functions. Water is held Together by hydrogen Bonds


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Cell_Biology_Alberts. Water is held Together by hydrogen Bonds The reactions inside a cell occur in an aqueous environment. Life on Earth began in the ocean, and the conditions in that primeval environment put a permanent stamp on the chemistry of living things. Life therefore hinges on the chemical properties of water, which are reviewed in Panel 2–2, pp. 92–93.


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Cell_Biology_Alberts. In each water molecule (H2O) the two H atoms are linked to the O atom by covalent bonds. The two bonds are highly polar because the O is strongly attractive for electrons, whereas the H is only weakly attractive. Consequently, there is an unequal distribution of electrons in a water molecule, with a preponderance of positive charge on the two H atoms and of negative charge on the O. When a positively charged region of one water molecule (that is, one of its H atoms) approaches a negatively charged region (that is, the O) of a second water molecule, the electrical attraction between them can result in a hydrogen bond. These bonds are much weaker than covalent bonds and are easily broken by the random thermal motions that reflect the heat energy of the molecules. Thus, each bond lasts only a short time. But the combined effect of many weak bonds can be profound. For example, each water molecule can form hydrogen bonds through its two H atoms to two other water molecules, producing a


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Cell_Biology_Alberts. a short time. But the combined effect of many weak bonds can be profound. For example, each water molecule can form hydrogen bonds through its two H atoms to two other water molecules, producing a network in which hydrogen bonds are being continually broken and formed. It is only because of the hydrogen bonds that link water molecules together that water is a liquid at room temperature—with a high boiling point and high surface tension—rather than a gas.


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Cell_Biology_Alberts. Molecules, such as alcohols, that contain polar bonds and that can form hydrogen bonds with water dissolve readily in water. Molecules carrying charges (ions) likewise interact favorably with water. Such molecules are termed hydrophilic, meaning that they are water-loving. Many of the molecules in the aqueous environment of a cell necessarily fall into this category, including sugars, DNA, RNA, and most proteins. Hydrophobic (water-hating) molecules, by contrast, are uncharged and form few or no hydrogen bonds, and so do not dissolve in water. Hydrocarbons are an important example. In these molecules all of the H atoms are covalently linked to C atoms by a largely nonpolar bond; thus they cannot form effective hydrogen bonds to other molecules (see Panel 2–1, p. 90). This makes the hydrocarbon as a whole hydrophobic—a property that is exploited in cells, whose membranes are constructed from molecules that have long hydrocarbon tails, as we see in Chapter 10.


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Cell_Biology_Alberts. four Types of noncovalent attractions help Bring molecules Together in Cells Much of biology depends on the specific binding of different molecules caused by three types of noncovalent bonds: electrostatic attractions (ionic bonds), hydrogen bonds, and van der Waals attractions; and on a fourth factor that can push molecules together: the hydrophobic force. The properties of the four types of noncovalent attractions are presented in Panel 2–3 (pp. 94–95). Although each


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Cell_Biology_Alberts. Figure 2–2 Some energies important for cells. a crucial property of any bond— covalent or noncovalent—is its strength. Bond strength is measured by the amount of energy that must be supplied to break it, expressed in units of either kilojoules per mole (kJ/mole) or kilocalories per mole (kcal/mole). Thus if 100 kJ of energy must be supplied to break 6 × 1023 bonds of a specific type (that is, 1 mole of these bonds), then the strength of that bond is 100 kJ/mole. note that, in this diagram, energies are compared on a logarithmic scale. Typical strengths and lengths of the main classes of chemical bonds are given in Table 2–1.


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Cell_Biology_Alberts. one joule (J) is the amount of energy required to move an object a distance of one meter against a force of one newton. This measure of energy is derived from the si units (système internationale d’Unités) universally employed by physical scientists. a second unit of energy, often used by cell biologists, is the kilocalorie (kcal); one calorie is the amount of energy needed to raise the temperature of 1 gram of water by 1°C. one kJ is equal to 0.239 kcal (1 kcal = 4.18 kJ). Figure 2–3 Schematic indicating how two macromolecules with complementary surfaces can bind tightly to one another through noncovalent interactions. noncovalent chemical bonds have less than 1/20 the strength of a covalent bond. They are able to produce tight binding only when many of them are formed simultaneously. although only electrostatic attractions are illustrated here, in reality all four noncovalent forces often contribute to holding two macromolecules together (Movie 2.1).


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Cell_Biology_Alberts. individual noncovalent attraction would be much too weak to be effective in the face of thermal motions, their energies can sum to create a strong force between two separate molecules. Thus sets of noncovalent attractions often allow the complementary surfaces of two macromolecules to hold those two macromolecules together (Figure 2–3). Table 2–1 compares noncovalent bond strengths to that of a typical covalent bond, both in the presence and in the absence of water. Note that, by forming competing interactions with the involved molecules, water greatly reduces the strength of both electrostatic attractions and hydrogen bonds.


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Cell_Biology_Alberts. The structure of a typical hydrogen bond is illustrated in Figure 2–4. This bond represents a special form of polar interaction in which an electropositive hydrogen atom is shared by two electronegative atoms. Its hydrogen can be viewed as a proton that has partially dissociated from a donor atom, allowing it to be shared by a second acceptor atom. Unlike a typical electrostatic interaction, this bond is highly directional—being strongest when a straight line can be drawn between all three of the involved atoms.


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Cell_Biology_Alberts. The fourth effect that often brings molecules together in water is not, strictly speaking, a bond at all. However, a very important hydrophobic force is caused by a pushing of nonpolar surfaces out of the hydrogen-bonded water network, where they would otherwise physically interfere with the highly favorable interactions between water molecules. Bringing any two nonpolar surfaces together reduces their contact with water; in this sense, the force is nonspecific. Nevertheless, we shall see in Chapter 3 that hydrophobic forces are central to the proper folding of protein molecules.


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Cell_Biology_Alberts. One of the simplest kinds of chemical reaction, and one that has profound significance in cells, takes place when a molecule containing a highly polar covalent bond between a hydrogen and another atom dissolves in water. The hydrogen atom in such a molecule has given up its electron almost entirely to the companion atom, and so exists as an almost naked positively charged hydrogen nucleus—in *an ionic bond is an electrostatic attraction between two fully charged atoms. **Values in parentheses are kcal/mole. 1 kJ = 0.239 kcal and 1 kcal = 4.18 kJ. (A) hydrogen bond ~0.3 nm long covalent bond ~0.1 nm long Figure 2–4 Hydrogen bonds. (a) Ball-andstick model of a typical hydrogen bond. The distance between the hydrogen and the oxygen atom here is less than the sum of their van der Waals radii, indicating a partial sharing of electrons. (B) The most common hydrogen bonds in cells.


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Cell_Biology_Alberts. H2O H2O molecule to H3O+ OH– the other hydronium hydroxyl(B) ion ion other words, a proton (H+). When the polar molecule becomes surrounded by water molecules, the proton will be attracted to the partial negative charge on the O atom of an adjacent water molecule. This proton can easily dissociate from its original partner and associate instead with the oxygen atom of the water molecule, generating a hydronium ion (H3O+) (Figure 2–5A). The reverse reaction also takes place very readily, so in the aqueous solution protons are constantly flitting to and fro between one molecule and another.


Cell_Biology_Alberts

Cell_Biology_Alberts. Substances that release protons when they dissolve in water, thus forming H3O+, are termed acids. The higher the concentration of H3O+, the more acidic the solution. H3O+ is present even in pure water, at a concentration of 10–7 M, as a result of the movement of protons from one water molecule to another (Figure 2–5B). By convention, the H3O+ concentration is usually referred to as the H+ concentration, even though most protons in an aqueous solution are present as H3O+. To avoid the use of unwieldy numbers, the concentration of H3O+ is expressed using a logarithmic scale called the pH scale. Pure water has a pH of 7.0 and is said to be neutral—that is, neither acidic (pH <7) nor basic (pH >7).


Cell_Biology_Alberts

Cell_Biology_Alberts. Acids are characterized as being strong or weak, depending on how readily they give up their protons to water. Strong acids, such as hydrochloric acid (HCl), lose their protons quickly. Acetic acid, on the other hand, is a weak acid because it holds on to its proton more tightly when dissolved in water. Many of the acids important in the cell—such as molecules containing a carboxyl (COOH) group— are weak acids (see Panel 2–2, pp. 92–93). Because the proton of a hydronium ion can be passed readily to many types of molecules in cells, altering their character, the concentration of H3O+ inside a cell (the acidity) must be closely regulated. Acids—especially weak acids—will give up their protons more readily if the concentration of H3O+ in solution is low and will tend to receive them back if the concentration in solution is high.


Cell_Biology_Alberts

Cell_Biology_Alberts. The opposite of an acid is a base. Any molecule capable of accepting a proton from a water molecule is called a base. Sodium hydroxide (NaOH) is basic (the term alkaline is also used) because it dissociates readily in aqueous solution to form Na+ ions and OH– ions. Because of this property, NaOH is called a strong base. More important in living cells, however, are the weak bases—those that have a weak tendency to reversibly accept a proton from water. Many biologically important molecules contain an amino (NH2) group. This group is a weak base that can generate OH– by taking a proton from water: –NH2 + H2O →–NH3+ + OH– (see Panel 2–2, pp. 92–93).


Cell_Biology_Alberts

Cell_Biology_Alberts. Because an OH– ion combines with a H3O+ ion to form two water molecules, an increase in the OH– concentration forces a decrease in the concentration of H3O+, and vice versa. A pure solution of water contains an equal concentration (10–7 M) of both ions, rendering it neutral. The interior of a cell is also kept close to neutrality by the presence of buffers: weak acids and bases that can release or take up protons near pH 7, keeping the environment of the cell relatively constant under a variety of conditions. Figure 2–5 Protons readily move in aqueous solutions. (a) The reaction that takes place when a molecule of acetic acid dissolves in water. at ph 7, nearly all of the acetic acid is present as acetate ion. (B) Water molecules are continuously exchanging protons with each other to form hydronium and hydroxyl ions. These ions in turn rapidly recombine to form water molecules. a Cell is formed from Carbon Compounds


Cell_Biology_Alberts

Cell_Biology_Alberts. a Cell is formed from Carbon Compounds Having reviewed the ways atoms combine into molecules and how these molecules behave in an aqueous environment, we now examine the main classes of small molecules found in cells. We shall see that a few categories of molecules, formed from a handful of different elements, give rise to all the extraordinary richness of form and behavior shown by living things.


Cell_Biology_Alberts

Cell_Biology_Alberts. If we disregard water and inorganic ions such as potassium, nearly all the molecules in a cell are based on carbon. Carbon is outstanding among all the elements in its ability to form large molecules; silicon is a poor second. Because carbon is small and has four electrons and four vacancies in its outermost shell, a carbon atom can form four covalent bonds with other atoms. Most important, one carbon atom can join to other carbon atoms through highly stable covalent C–C bonds to form chains and rings and hence generate large and complex molecules with no obvious upper limit to their size. The carbon compounds made by cells are called organic molecules. In contrast, all other molecules, including water, are said to be inorganic.


Cell_Biology_Alberts

Cell_Biology_Alberts. Certain combinations of atoms, such as the methyl (–CH3), hydroxyl (–OH), carboxyl (–COOH), carbonyl (–C=O), phosphate (–PO32–), sulfhydryl (–SH), and amino (–NH2) groups, occur repeatedly in the molecules made by cells. Each such chemical group has distinct chemical and physical properties that influence the behavior of the molecule in which the group occurs. The most common chemical groups and some of their properties are summarized in Panel 2–1, pp. 90–91. Cells Contain four major families of small organic molecules


Cell_Biology_Alberts

Cell_Biology_Alberts. Cells Contain four major families of small organic molecules The small organic molecules of the cell are carbon-based compounds that have molecular weights in the range of 100–1000 and contain up to 30 or so carbon atoms. They are usually found free in solution and have many different fates. Some are used as monomer subunits to construct giant polymeric macromolecules— proteins, nucleic acids, and large polysaccharides. Others act as energy sources and are broken down and transformed into other small molecules in a maze of intracellular metabolic pathways. Many small molecules have more than one role in the cell—for example, acting both as a potential subunit for a macromolecule and as an energy source. Small organic molecules are much less abundant than the organic macromolecules, accounting for only about one-tenth of the total mass of organic matter in a cell. As a rough guess, there may be a thousand different kinds of these small molecules in a typical cell.


Cell_Biology_Alberts

Cell_Biology_Alberts. All organic molecules are synthesized from and are broken down into the same set of simple compounds. As a consequence, the compounds in a cell are chemically related and most can be classified into a few distinct families. Broadly speaking, cells contain four major families of small organic molecules: the sugars, the fatty acids, the nucleotides, and the amino acids (Figure 2–6). Although many compounds present in cells do not fit into these categories, these four families of small organic molecules, together with the macromolecules made by linking them into long chains, account for a large fraction of the cell mass. Amino acids and the proteins that they form will be the subject of Chapter 3. A summary of the structures and properties of the remaining three families— sugars, fatty acids, and nucleotides—is presented in Panels 2–4, 2–5, and 2–6, respectively (see pages 96–101). The Chemistry of Cells is Dominated by macromolecules with Remarkable properties


Cell_Biology_Alberts

Cell_Biology_Alberts. The Chemistry of Cells is Dominated by macromolecules with Remarkable properties By weight, macromolecules are the most abundant carbon-containing molecules in a living cell (Figure 2–7). They are the principal building blocks from which a cell is constructed and also the components that confer the most distinctive properties of living things. The macromolecules in cells are polymers that are constructed by covalently linking small organic molecules (called monomers) into of the cell of the cell SUGARS FATTY ACIDS POLYSACCHARIDES AMINO ACIDS NUCLEOTIDES PROTEINS FATS, LIPIDS, MEMBRANES NUCLEIC ACIDS


Cell_Biology_Alberts

Cell_Biology_Alberts. SUGARS FATTY ACIDS POLYSACCHARIDES AMINO ACIDS NUCLEOTIDES PROTEINS FATS, LIPIDS, MEMBRANES NUCLEIC ACIDS Figure 2–6 The four main families of small organic molecules in cells. These small molecules form the monomeric building blocks, or subunits, for most of the macromolecules and other assemblies of the cell. some, such as the sugars and the fatty acids, are also energy sources. Their structures are outlined here and shown in more detail in the panels at the end of this chapter and in Chapter 3. long chains (Figure 2–8). They have remarkable properties that could not have been predicted from their simple constituents.


Cell_Biology_Alberts

Cell_Biology_Alberts. long chains (Figure 2–8). They have remarkable properties that could not have been predicted from their simple constituents. Proteins are abundant and spectacularly versatile, performing thousands of distinct functions in cells. Many proteins serve as enzymes, the catalysts that facilitate the many covalent bond-making and bond-breaking reactions that the cell needs. Enzymes catalyze all of the reactions whereby cells extract energy from food molecules, for example, and an enzyme called ribulose bisphosphate carboxylase helps to convert CO2 to sugars in photosynthetic organisms, producing most of the organic matter needed for life on Earth. Other proteins are used to build structural components, such as tubulin, a protein that self-assembles to make the cell’s long microtubules, or histones, proteins that compact the DNA in chromosomes. Yet other proteins act as molecular motors to produce force and


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 2–7 The distribution of molecules in cells. The approximate composition of a bacterial cell is shown by weight. The composition of an animal cell is similar, even though its volume is roughly 1000 times greater. note that macromolecules dominate. The major inorganic ions include na+, K+, mg2+, Ca2+, and Cl–. movement, as for myosin in muscle. Proteins perform many other functions, and we shall examine the molecular basis for many of them later in this book.


Cell_Biology_Alberts

Cell_Biology_Alberts. Although the chemical reactions for adding subunits to each polymer are different in detail for proteins, nucleic acids, and polysaccharides, they share important features. Each polymer grows by the addition of a monomer onto the end of a growing chain in a condensation reaction, in which one molecule of water is lost with each subunit added (Figure 2–9). The stepwise polymerization of monomers into a long chain is a simple way to manufacture a large, complex molecule, since the subunits are added by the same reaction performed over and over again by the same set of enzymes. Apart from some of the polysaccharides, most macromolecules are made from a limited set of monomers that are slightly different from one another—for example, the 20 different amino acids from which proteins are made. It is critical to life that the polymer chain is not assembled at random from these subunits; instead the subunits are added in a precise order, or sequence. The elaborate mechanisms that allow


Cell_Biology_Alberts

Cell_Biology_Alberts. made. It is critical to life that the polymer chain is not assembled at random from these subunits; instead the subunits are added in a precise order, or sequence. The elaborate mechanisms that allow enzymes to accomplish this task are described in detail in Chapters 5 and 6.


Cell_Biology_Alberts

Cell_Biology_Alberts. noncovalent Bonds specify Both the precise shape of a macromolecule and its Binding to other molecules Most of the covalent bonds in a macromolecule allow rotation of the atoms they join, giving the polymer chain great flexibility. In principle, this allows a macromolecule to adopt an almost unlimited number of shapes, or conformations, as random thermal energy causes the polymer chain to writhe and rotate. However, the shapes of most biological macromolecules are highly constrained because of the many weak noncovalent bonds that form between different parts of the same molecule. If these noncovalent bonds are formed in sufficient numbers, the polymer chain can strongly prefer one particular conformation, determined by the linear sequence of monomers in its chain. Most protein molecules and many of the small RNA molecules found in cells fold tightly into a highly preferred conformation in this way (Figure 2–10).


Cell_Biology_Alberts

Cell_Biology_Alberts. The four types of noncovalent interactions important in biological molecules were presented earlier, and they are discussed further in Panel 2–3 (pp. 94–95). In addition to folding biological macromolecules into unique shapes, they can also add up to create a strong attraction between two different molecules (see Figure 2–3). This form of molecular interaction provides for great specificity, inasmuch as the close multipoint contacts required for strong binding make it possible for a macromolecule to select out—through binding—just one of the many thousands of other types of molecules present inside a cell. Moreover, because the strength of the binding depends on the number of noncovalent bonds that are formed, interactions of almost any affinity are possible—allowing rapid dissociation where appropriate.


Cell_Biology_Alberts

Cell_Biology_Alberts. As we discuss next, binding of this type underlies all biological catalysis, making it possible for proteins to function as enzymes. In addition, noncovalent interactions allow macromolecules to be used as building blocks for the formation of Figure 2–8 Three families of macromolecules. each is a polymer formed from small molecules (called monomers) linked together by covalent bonds. Figure 2–9 Condensation and hydrolysis as opposite reactions. The macromolecules of the cell are polymers that are formed from subunits (or monomers) by a condensation reaction, and they are broken down by hydrolysis. The condensation reactions are all energetically unfavorable; thus polymer formation requires an energy input, as will be described in the text.


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Cell_Biology_Alberts. Figure 2–10 The folding of proteins and RNa molecules into a particularly stable three-dimensional shape, or conformation. if the noncovalent bonds maintaining the stable conformation are disrupted, the molecule becomes a flexible chain that loses its biological activity. larger structures, thereby forming intricate machines with multiple moving parts that perform such complex tasks as DNA replication and protein synthesis (Figure 2–11).


Cell_Biology_Alberts

Cell_Biology_Alberts. Living organisms are autonomous, self-propagating chemical systems. They are formed from a distinctive and restricted set of small carbon-based molecules that are essentially the same for every living species. Each of these small molecules is composed of a small set of atoms linked to each other in a precise configuration through covalent bonds. The main categories are sugars, fatty acids, amino acids, and nucleotides. Sugars are a primary source of chemical energy for cells and can be incorporated into polysaccharides for energy storage. Fatty acids are also important for energy storage, but their most critical function is in the formation of cell membranes. Long chains of amino acids form the remarkably diverse and versatile macromolecules known as proteins. Nucleotides play a central part in energy transfer, while also serving as the subunits for the informational macromolecules, RNA and DNA.


Cell_Biology_Alberts

Cell_Biology_Alberts. Most of the dry mass of a cell consists of macromolecules that have been produced as linear polymers of amino acids (proteins) or nucleotides (DNA and RNA), covalently linked to each other in an exact order. Most of the protein molecules and many of the RNAs fold into a unique conformation that is determined by their sequence of subunits. This folding process creates unique surfaces, and it depends on a large set of weak attractions produced by noncovalent forces between atoms. e.g., sugars, amino acids, and nucleotides e.g., globular proteins and RNA e.g., ribosome Figure 2–11 Small molecules become covalently linked to form macromolecules, which in turn assemble through noncovalent interactions to form large complexes. small molecules, proteins, and a ribosome are drawn approximately to scale. Ribosomes are a central part of the machinery that the cell uses to make proteins: each ribosome is formed as a complex of about 90 macromolecules (protein and Rna molecules).


Cell_Biology_Alberts

Cell_Biology_Alberts. These forces are of four types: electrostatic attractions, hydrogen bonds, van der Waals attractions, and an interaction between nonpolar groups caused by their hydrophobic expulsion from water. The same set of weak forces governs the specific binding of other molecules to macromolecules, making possible the myriad associations between biological molecules that produce the structure and the chemistry of a cell. CaTalYsis anD The Use of eneRGY BY Cells


Cell_Biology_Alberts

Cell_Biology_Alberts. CaTalYsis anD The Use of eneRGY BY Cells One property of living things above all makes them seem almost miraculously different from nonliving matter: they create and maintain order, in a universe that is tending always to greater disorder (Figure 2–12). To create this order, the cells in a living organism must perform a never-ending stream of chemical reactions. In some of these reactions, small organic molecules—amino acids, sugars, nucleotides, and lipids—are being taken apart or modified to supply the many other small molecules that the cell requires. In other reactions, small molecules are being used to construct an enormously diverse range of proteins, nucleic acids, and other macromolecules that endow living systems with all of their most distinctive properties. Each cell can be viewed as a tiny chemical factory, performing many millions of reactions every second. Cell metabolism is organized by enzymes


Cell_Biology_Alberts

Cell_Biology_Alberts. Cell metabolism is organized by enzymes The chemical reactions that a cell carries out would normally occur only at much higher temperatures than those existing inside cells. For this reason, each reaction requires a specific boost in chemical reactivity. This requirement is crucial, because it allows the cell to control its chemistry. The control is exerted through specialized biological catalysts. These are almost always proteins called enzymes, although RNA catalysts also exist, called ribozymes. Each enzyme accelerates, or catalyzes, just one of the many possible kinds of reactions that a particular molecule might undergo. Enzyme-catalyzed reactions are connected in series, so that the product of one reaction becomes the starting material, or substrate, for the next (Figure 2–13). Long linear reaction pathways are in turn linked to one another, forming a maze of interconnected reactions that enable the cell to survive, grow, and reproduce.


Cell_Biology_Alberts

Cell_Biology_Alberts. Two opposing streams of chemical reactions occur in cells: (1) the catabolic pathways break down foodstuffs into smaller molecules, thereby generating both a useful form of energy for the cell and some of the small molecules that the cell needs as building blocks, and (2) the anabolic, or biosynthetic, pathways use the 20 nm 50 nm 10 µm 0.5 mm 20 mm


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 2–12 biological structures are highly ordered. Well-defined, ornate, and beautiful spatial patterns can be found at every level of organization in living organisms. in order of increasing size: (a) protein molecules in the coat of a virus (a parasite that, although not technically alive, contains the same types of molecules as those found in living cells); (B) the regular array of microtubules seen in a cross section of a sperm tail; (C) surface contours of a pollen grain (a single cell); (D) cross section of a fern stem, showing the patterned arrangement of cells; and (e) a spiral arrangement of leaves in a succulent plant. (a, courtesy of Robert Grant, stéphane Crainic, and James m. hogle; B, courtesy of lewis Tilney; C, courtesy of Colin macfarlane and Chris Jeffree; D, courtesy of Jim haseloff.)


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 2–13 How a set of enzyme-catalyzed reactions generates a metabolic pathway. each enzyme catalyzes a particular chemical reaction, leaving the enzyme unchanged. in this example, a set of enzymes acting in series converts molecule a to molecule f, forming a metabolic pathway. (for a diagram of many of the reactions in a human cell, abbreviated as shown, see figure 2–63.) small molecules and the energy harnessed by catabolism to drive the synthesis of the many other molecules that form the cell. Together these two sets of reactions constitute the metabolism of the cell (Figure 2–14). The details of cell metabolism form the traditional subject of biochemistry and most of them need not concern us here. But the general principles by which cells obtain energy from their environment and use it to create order are central to cell biology. We begin with a discussion of why a constant input of energy is needed to sustain all living things.


Cell_Biology_Alberts

Cell_Biology_Alberts. Biological order is made possible by the Release of heat energy from Cells The universal tendency of things to become disordered is a fundamental law of physics—the second law of thermodynamics—which states that in the universe, or in any isolated system (a collection of matter that is completely isolated from the rest of the universe), the degree of disorder always increases. This law has such profound implications for life that we will restate it in several ways.


Cell_Biology_Alberts

Cell_Biology_Alberts. For example, we can present the second law in terms of probability by stating that systems will change spontaneously toward those arrangements that have the greatest probability. If we consider a box of 100 coins all lying heads up, a series of accidents that disturbs the box will tend to move the arrangement toward a mixture of 50 heads and 50 tails. The reason is simple: there is a huge number of possible arrangements of the individual coins in the mixture that can achieve the 50–50 result, but only one possible arrangement that keeps all of the coins oriented heads up. Because the 50–50 mixture is therefore the most probable, we say that it is more “disordered.” For the same reason, it is a common experience that one’s living space will become increasingly disordered without intentional effort: the movement toward disorder is a spontaneous process, requiring a periodic effort to reverse it (Figure 2–15).


Cell_Biology_Alberts

Cell_Biology_Alberts. The amount of disorder in a system can be quantified and expressed as the entropy of the system: the greater the disorder, the greater the entropy. Thus, another way to express the second law of thermodynamics is to say that systems will change spontaneously toward arrangements with greater entropy.


Cell_Biology_Alberts

Cell_Biology_Alberts. Living cells—by surviving, growing, and forming complex organisms—are generating order and thus might appear to defy the second law of thermodynamics. How is this possible? The answer is that a cell is not an isolated system: it takes in energy from its environment in the form of food, or as photons from the sun (or even, as in some chemosynthetic bacteria, from inorganic molecules alone). It then uses this energy to generate order within itself. In the course of the chemical reactions that generate order, the cell converts part of the energy it uses into heat. The heat is discharged into the cell’s environment and disorders the surroundings. As a result, the total entropy—that of the cell plus its surroundings—increases, as demanded by the second law of thermodynamics.


Cell_Biology_Alberts

Cell_Biology_Alberts. To understand the principles governing these energy conversions, think of a cell surrounded by a sea of matter representing the rest of the universe. As the cell lives and grows, it creates internal order. But it constantly releases heat energy as it synthesizes molecules and assembles them into cell structures. Heat is energy in its most disordered form—the random jostling of molecules. When food the many molecules molecules that form the cell Figure 2–14 Schematic representation of the relationship between catabolic and anabolic pathways in metabolism. as suggested in this diagram, a major portion of the energy stored in the chemical bonds of food molecules is dissipated as heat. in addition, the mass of food required by any organism that derives all of its energy from catabolism is much greater than the mass of the molecules that it can produce by anabolism.


Cell_Biology_Alberts

Cell_Biology_Alberts. the cell releases heat to the sea, it increases the intensity of molecular motions there (thermal motion)—thereby increasing the randomness, or disorder, of the sea. The second law of thermodynamics is satisfied because the increase in the amount of order inside the cell is always more than compensated for by an even greater decrease in order (increase in entropy) in the surrounding sea of matter (Figure 2–16).


Cell_Biology_Alberts

Cell_Biology_Alberts. Where does the heat that the cell releases come from? Here we encounter another important law of thermodynamics. The first law of thermodynamics states that energy can be converted from one form to another, but that it cannot be created or destroyed. Figure 2–17 illustrates some interconversions between different forms of energy. The amount of energy in different forms will change as a result of the chemical reactions inside the cell, but the first law tells us that the total amount of energy must always be the same. For example, an animal cell takes in foodstuffs and converts some of the energy present in the chemical bonds between the atoms of these food molecules (chemical-bond energy) into the random thermal motion of molecules (heat energy).


Cell_Biology_Alberts

Cell_Biology_Alberts. The cell cannot derive any benefit from the heat energy it releases unless the heat-generating reactions inside the cell are directly linked to the processes that generate molecular order. It is the tight coupling of heat production to an increase sea of matter cell Figure 2–15 an everyday illustration of the spontaneous drive toward disorder. Reversing this tendency toward disorder requires an intentional effort and an input of energy: it is not spontaneous. in fact, from the second law of thermodynamics, we can be certain that the human intervention required will release enough heat to the environment to more than compensate for the reordering of the items in this room.


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 2–16 a simple thermodynamic analysis of a living cell. in the diagram on the left, the molecules of both the cell and the rest of the universe (the sea of matter) are depicted in a relatively disordered state. in the diagram on the right, the cell has taken in energy from food molecules and released heat through reactions that order the molecules the cell contains. The heat released increases the disorder in the environment around the cell (depicted by jagged arrows and distorted molecules, indicating increased molecular motions caused by heat). as a result, the second law of thermodynamics—which states that the amount of disorder in the universe must always increase—is satisfied as the cell grows and divides. for a detailed discussion, see panel 2–7 (pp. 102–103).