Cell_Biology_Alberts

Cell_Biology_Alberts. The surface of our planet is populated by living things—curious, intricately organized chemical factories that take in matter from their surroundings and use these raw materials to generate copies of themselves. These living organisms appear extraordinarily diverse. What could be more different than a tiger and a piece of seaweed, or a bacterium and a tree? Yet our ancestors, knowing nothing of cells or DNA, saw that all these things had something in common. They called that something “life,” marveled at it, struggled to define it, and despaired of explaining what it was or how it worked in terms that relate to nonliving matter.


Cell_Biology_Alberts

Cell_Biology_Alberts. The discoveries of the past century have not diminished the marvel—quite the contrary. But they have removed the central mystery regarding the nature of life. We can now see that all living things are made of cells: small, membrane-enclosed units filled with a concentrated aqueous solution of chemicals and endowed with the extraordinary ability to create copies of themselves by growing and then dividing in two.


Cell_Biology_Alberts

Cell_Biology_Alberts. Because cells are the fundamental units of life, it is to cell biology—the study of the structure, function, and behavior of cells—that we must look for answers to the questions of what life is and how it works. With a deeper understanding of cells and their evolution, we can begin to tackle the grand historical problems of life on Earth: its mysterious origins, its stunning diversity, and its invasion of every conceivable habitat. Indeed, as emphasized long ago by the pioneering cell biologist E. B. Wilson, “the key to every biological problem must finally be sought in the cell; for every living organism is, or at some time has been, a cell.”


Cell_Biology_Alberts

Cell_Biology_Alberts. Despite their apparent diversity, living things are fundamentally similar inside. The whole of biology is thus a counterpoint between two themes: astonishing variety in individual particulars; astonishing constancy in fundamental mechanisms. In this first chapter, we begin by outlining the universal features common to all life on our planet. We then survey, briefly, the diversity of cells. And we see how, thanks to the common molecular code in which the specifications for all living organisms are written, it is possible to read, measure, and decipher these specifications to help us achieve a coherent understanding of all the forms of life, from the smallest to the greatest. The unIveRsAl FeATuRes oF cells on eARTh The dIveRsITy oF Genomes And The TRee oF lIFe The unIveRsAl FeATuRes oF cells on eARTh


Cell_Biology_Alberts

Cell_Biology_Alberts. The unIveRsAl FeATuRes oF cells on eARTh It is estimated that there are more than 10 million—perhaps 100 million—living species on Earth today. Each species is different, and each reproduces itself faithfully, yielding progeny that belong to the same species: the parent organism hands down information specifying, in extraordinary detail, the characteristics that the offspring shall have. This phenomenon of heredity is central to the definition of life: it distinguishes life from other processes, such as the growth of a crystal, or the burning of a candle, or the formation of waves on water, in which orderly structures are generated but without the same type of link between the peculiarities of parents and the peculiarities of offspring. Like the candle flame, the living organism must consume free energy to create and maintain its organization. But life employs the free energy to drive a hugely complex system of chemical processes that are specified by hereditary information.


Cell_Biology_Alberts

Cell_Biology_Alberts. Most living organisms are single cells. Others, such as ourselves, are vast multicellular cities in which groups of cells perform specialized functions linked by intricate systems of communication. But even for the aggregate of more than 1013 cells that form a human body, the whole organism has been generated by cell divisions from a single cell. The single cell, therefore, is the vehicle for all of the hereditary information that defines each species (Figure 1–1). This cell includes the machinery to gather raw materials from the environment and to construct from them a new cell in its own image, complete with a new copy of its hereditary information. Each and every cell is truly amazing. All cells store Their hereditary Information in the same linear chemical code: dnA


Cell_Biology_Alberts

Cell_Biology_Alberts. All cells store Their hereditary Information in the same linear chemical code: dnA Computers have made us familiar with the concept of information as a measurable quantity—a million bytes (to record a few hundred pages of text or an image from a digital camera), 600 million bytes for the music on a CD, and so on. Computers have also made us well aware that the same information can be recorded in many different physical forms: the discs and tapes that we used 20 years ago for our electronic archives have become unreadable on present-day machines. Living


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 1–1 The hereditary information in the fertilized egg cell determines the nature of the whole multicellular organism. Although their starting cells look superficially similar, as indicated: a sea urchin egg gives rise to a sea urchin (A and B). A mouse egg gives rise to a mouse (c and d). An egg of the seaweed Fucus gives rise to a Fucus seaweed (e and F). (A, courtesy of david mcclay; B, courtesy of m. Gibbs, oxford scientific Films; c, courtesy of Patricia calarco, from G. martin, Science 209:768–776, 1980. With permission from AAAs; d, courtesy of o. newman, oxford scientific Films; e and F, courtesy of colin Brownlee.) (A) building block of DNA (D) double-stranded DNA (C) templated polymerization of new strand cells, like computers, store information, and it is estimated that they have been evolving and diversifying for over 3.5 billion years. It is scarcely to be expected that they would all store their information in the same form, or that the archives of one type of


Cell_Biology_Alberts

Cell_Biology_Alberts. they have been evolving and diversifying for over 3.5 billion years. It is scarcely to be expected that they would all store their information in the same form, or that the archives of one type of cell should be readable by the information-handling machinery of another. And yet it is so. All living cells on Earth store their hereditary information in the form of double-stranded molecules of DNA—long, unbranched, paired polymer chains, formed always of the same four types of monomers. These monomers, chemical compounds known as nucleotides, have nicknames drawn from a four-letter alphabet—A, T, C, G—and they are strung together in a long linear sequence that encodes the genetic information, just as the sequence of 1s and 0s encodes the information in a computer file. We can take a piece of DNA from a human cell and insert it into a bacterium, or a piece of bacterial DNA and insert it into a human cell, and the information will be successfully read, interpreted, and copied. Using


Cell_Biology_Alberts

Cell_Biology_Alberts. of DNA from a human cell and insert it into a bacterium, or a piece of bacterial DNA and insert it into a human cell, and the information will be successfully read, interpreted, and copied. Using chemical methods, scientists have learned how to read out the complete sequence of monomers in any DNA molecule—extending for many millions of nucleotides—and thereby decipher all of the hereditary information that each organism contains.


Cell_Biology_Alberts

Cell_Biology_Alberts. The mechanisms that make life possible depend on the structure of the double-stranded DNA molecule. Each monomer in a single DNA strand—that is, each nucleotide—consists of two parts: a sugar (deoxyribose) with a phosphate group attached to it, and a base, which may be either adenine (A), guanine (G), cytosine (C), or thymine (T) (Figure 1–2). Each sugar is linked to the next via the phosphate group, creating a polymer chain composed of a repetitive sugar-phosphate backbone with a series of bases protruding from it. The DNA polymer is extended by adding monomers at one end. For a single isolated strand, these monomers can, in principle, be added in any order, because each one links to the next in the same way, through the part of the molecule that is the same for all of them. In the living cell, however, DNA is not synthesized as a free strand in isolation, but on a template formed by a preexisting DNA strand. The bases protruding from the Figure 1–2 DNA and its building blocks.


Cell_Biology_Alberts

Cell_Biology_Alberts. (A) dnA is made from simple subunits, called nucleotides, each consisting of a sugar-phosphate molecule with a nitrogen-containing side group, or base, attached to it. The bases are of four types (adenine, guanine, cytosine, and thymine), corresponding to four distinct nucleotides, labeled A, G, c, and T. (B) A single strand of dnA consists of nucleotides joined together by sugar-phosphate linkages. note that the individual sugar-phosphate units are asymmetric, giving the backbone of the strand a definite directionality, or polarity. This directionality guides the molecular processes by which the information in dnA is interpreted and copied in cells: the information is always “read” in a consistent order, just as written english text is read from left to right. (c) Through templated polymerization, the sequence of nucleotides in an existing dnA strand controls the sequence in which nucleotides are joined together in a new dnA strand; T in one strand pairs with A in the other, and G in


Cell_Biology_Alberts

Cell_Biology_Alberts. the sequence of nucleotides in an existing dnA strand controls the sequence in which nucleotides are joined together in a new dnA strand; T in one strand pairs with A in the other, and G in one strand with c in the other. The new strand has a nucleotide sequence complementary to that of the old strand, and a backbone with opposite directionality: corresponding to the GTAA... of the original strand, it has ...TTAc. (d) A normal dnA molecule consists of two such complementary strands. The nucleotides within each strand are linked by strong (covalent) chemical bonds; the complementary nucleotides on opposite strands are held together more weakly, by hydrogen bonds. (e) The two strands twist around each other to form a double helix—a robust structure that can accommodate any sequence of nucleotides without altering its basic structure (see movie 4.1).


Cell_Biology_Alberts

Cell_Biology_Alberts. existing strand bind to bases of the strand being synthesized, according to a strict rule defined by the complementary structures of the bases: A binds to T, and C binds to G. This base-pairing holds fresh monomers in place and thereby controls the selection of which one of the four monomers shall be added to the growing strand next. In this way, a double-stranded structure is created, consisting of two exactly complementary sequences of As, Cs, Ts, and Gs. The two strands twist around each other, forming a DNA double helix (Figure 1–2E).


Cell_Biology_Alberts

Cell_Biology_Alberts. The bonds between the base pairs are weak compared with the sugar-phosphate links, and this allows the two DNA strands to be pulled apart without breakage of their backbones. Each strand then can serve as a template, in the way just described, for the synthesis of a fresh DNA strand complementary to itself—a fresh copy, that is, of the hereditary information (Figure 1–3). In different types of cells, this process of DNA replication occurs at different rates, with different controls to start it or stop it, and different auxiliary molecules to help it along. But the basics are universal: DNA is the information store for heredity, and templated polymerization is the way in which this information is copied throughout the living world. All cells Transcribe Portions of Their hereditary Information into the same Intermediary Form: RnA


Cell_Biology_Alberts

Cell_Biology_Alberts. All cells Transcribe Portions of Their hereditary Information into the same Intermediary Form: RnA To carry out its information-bearing function, DNA must do more than copy itself. It must also express its information, by letting the information guide the synthesis of other molecules in the cell. This expression occurs by a mechanism that is the same in all living organisms, leading first and foremost to the production of two other key classes of polymers: RNAs and proteins. The process (discussed in detail in Chapters 6 and 7) begins with a templated polymerization called transcription, in which segments of the DNA sequence are used as templates for the synthesis of shorter molecules of the closely related polymer ribonucleic acid, or RNA. Later, in the more complex process of translation, many of these RNA molecules direct the synthesis of polymers of a radically different chemical class—the proteins (Figure 1–4).


Cell_Biology_Alberts

Cell_Biology_Alberts. In RNA, the backbone is formed of a slightly different sugar from that of DNA— ribose instead of deoxyribose—and one of the four bases is slightly different—uracil (U) in place of thymine (T). But the other three bases—A, C, and G—are the same, and all four bases pair with their complementary counterparts in DNA—the A, U, C, and G of RNA with the T, A, G, and C of DNA. During transcription, the RNA monomers are lined up and selected for polymerization on a template strand of DNA, just as DNA monomers are selected during replication. The outcome is a polymer molecule whose sequence of nucleotides faithfully represents a portion of the cell’s genetic information, even though it is written in a slightly different alphabet—consisting of RNA monomers instead of DNA monomers.


Cell_Biology_Alberts

Cell_Biology_Alberts. The same segment of DNA can be used repeatedly to guide the synthesis of many identical RNA molecules. Thus, whereas the cell’s archive of genetic information in the form of DNA is fixed and sacrosanct, these RNA transcripts are Figure 1–3 The copying of genetic information by DNA replication. In this process, the two strands of a dnA double helix are pulled apart, and each serves as a template for synthesis of a new complementary strand. Figure 1–4 From DNA to protein. Genetic information is read out and put to use through a two-step process. First, in transcription, segments of the dnA sequence are used to guide the synthesis of molecules of RnA. Then, in translation, the RnA molecules are used to guide the synthesis of molecules of protein.


Cell_Biology_Alberts

Cell_Biology_Alberts. strand used as a template to direct RNA synthesis many identical RNA transcripts mass-produced and disposable (Figure 1–5). As we shall see, these transcripts function as intermediates in the transfer of genetic information. Most notably, they serve as messenger RNA (mRNA) molecules that guide the synthesis of proteins according to the genetic instructions stored in the DNA.


Cell_Biology_Alberts

Cell_Biology_Alberts. RNA molecules have distinctive structures that can also give them other specialized chemical capabilities. Being single-stranded, their backbone is flexible, so that the polymer chain can bend back on itself to allow one part of the molecule to form weak bonds with another part of the same molecule. This occurs when segments of the sequence are locally complementary: a ...GGGG... segment, for example, will tend to associate with a ...CCCC... segment. These types of internal associations can cause an RNA chain to fold up into a specific shape that is dictated by its sequence (Figure 1–6). The shape of the RNA molecule, in turn, may enable it to recognize other molecules by binding to them selectively—and even, in certain cases, to catalyze chemical changes in the molecules that are bound. In fact, some chemical reactions catalyzed by RNA molecules are crucial for several of the most ancient and fundamental processes in living cells, and it has been suggested that an extensive catalysis


Cell_Biology_Alberts

Cell_Biology_Alberts. fact, some chemical reactions catalyzed by RNA molecules are crucial for several of the most ancient and fundamental processes in living cells, and it has been suggested that an extensive catalysis by RNA played a central part in the early evolution of life (discussed in Chapter 6).


Cell_Biology_Alberts

Cell_Biology_Alberts. All cells use Proteins as catalysts Protein molecules, like DNA and RNA molecules, are long unbranched polymer chains, formed by stringing together monomeric building blocks drawn from a standard repertoire that is the same for all living cells. Like DNA and RNA, proteins carry information in the form of a linear sequence of symbols, in the same way as a human message written in an alphabetic script. There are many different protein molecules in each cell, and—leaving out the water—they form most of the cell’s mass. Figure 1–5 How genetic information is broadcast for use inside the cell.


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 1–5 How genetic information is broadcast for use inside the cell. each cell contains a fixed set of dnA molecules—its archive of genetic information. A given segment of this dnA guides the synthesis of many identical RnA transcripts, which serve as working copies of the information stored in the archive. many different sets of RnA molecules can be made by transcribing different parts of a cell’s dnA sequences, allowing different types of cells to use the same information store differently.


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 1–6 The conformation of an RNA molecule. (A) nucleotide pairing between different regions of the same RnA polymer chain causes the molecule to adopt a distinctive shape. (B) The three-dimensional structure of an actual RnA molecule produced by hepatitis delta virus; this RnA can catalyze RnA strand cleavage. The blue ribbon represents the sugar-phosphate backbone and the bars represent base pairs (see movie 6.1). (B, based on A.R. Ferré-d’Amaré, k. Zhou, and J.A. doudna, Nature 395:567–574, 1998. With permission from macmillan Publishers ltd.) Figure 1–7 How a protein molecule acts as a catalyst for a chemical reaction. (A) In a protein molecule, the polymer chain folds up into a specific shape defined by its amino acid sequence. A groove in the surface of this particular folded molecule, the enzyme lysozyme, forms a catalytic site.


Cell_Biology_Alberts

Cell_Biology_Alberts. (B) A polysaccharide molecule (red)—a polymer chain of sugar monomers—binds to the catalytic site of lysozyme and is broken apart, as a result of a covalent bond-breaking reaction catalyzed by the amino acids lining the groove (see movie 3.9). (PdB code: 1lyd.)


Cell_Biology_Alberts

Cell_Biology_Alberts. The monomers of protein, the amino acids, are quite different from those of DNA and RNA, and there are 20 types instead of 4. Each amino acid is built around the same core structure through which it can be linked in a standard way to any other amino acid in the set; attached to this core is a side group that gives each amino acid a distinctive chemical character. Each of the protein molecules is a polypeptide, created by joining its amino acids in a particular sequence. Through billions of years of evolution, this sequence has been selected to give the protein a useful function. Thus, by folding into a precise three-dimensional form with reactive sites on its surface (Figure 1–7A), these amino-acid polymers can bind with high specificity to other molecules and can act as enzymes to catalyze reactions that make or break covalent bonds. In this way they direct the vast majority of chemical processes in the cell (Figure 1–7B).


Cell_Biology_Alberts

Cell_Biology_Alberts. Proteins have many other functions as well—maintaining structures, generating movements, sensing signals, and so on—each protein molecule performing a specific function according to its own genetically specified sequence of amino acids. Proteins, above all, are the main molecules that put the cell’s genetic information into action. Thus, polynucleotides specify the amino acid sequences of proteins. Proteins, in turn, catalyze many chemical reactions, including those by which new DNA molecules are synthesized. From the most fundamental point of view, a living cell is a self-replicating collection of catalysts that takes in food, processes this food to derive both the building blocks and energy needed to make more catalysts, and discards the materials left over as waste (Figure 1–8A). A feedback loop that connects proteins and polynucleotides forms the basis for this autocatalytic, self-reproducing behavior of living organisms (Figure 1–8B).


Cell_Biology_Alberts

Cell_Biology_Alberts. All cells Translate RnA into Protein in the same Way How the information in DNA specifies the production of proteins was a complete mystery in the 1950s when the double-stranded structure of DNA was first revealed as the basis of heredity. But in the intervening years, scientists have discovered the elegant mechanisms involved. The translation of genetic information from the 4-letter alphabet of polynucleotides into the 20-letter alphabet of proteins is a complex process. The rules of this translation seem in some respects neat and rational but in other respects strangely arbitrary, given that they are (with minor exceptions) identical in all living things. These arbitrary features, it is thought, reflect frozen accidents in the early history of life. They stem from the chance properties of the earliest organisms that were passed on by heredity and have become so deeply embedded in the constitution of all living cells that they cannot be changed without disastrous effects.


Cell_Biology_Alberts

Cell_Biology_Alberts. It turns out that the information in the sequence of a messenger RNA molecule is read out in groups of three nucleotides at a time: each triplet of nucleotides, or codon, specifies (codes for) a single amino acid in a corresponding protein. Since the number of distinct triplets that can be formed from four nucleotides is 43, there are 64 possible codons, all of which occur in nature. However, there are only 20 naturally occurring amino acids. That means there are necessarily many cases in which several codons correspond to the same amino acid. This genetic code is read out by a special class of small RNA molecules, the transfer RNAs (tRNAs). Each type of tRNA becomes attached at one end to a specific amino acid, and displays at its other end a specific sequence of three nucleotides—an anticodon— that enables it to recognize, through base-pairing, a particular codon or subset of codons in mRNA. The intricate chemistry that enables these tRNAs to translate a specific sequence of A, C,


Cell_Biology_Alberts

Cell_Biology_Alberts. that enables it to recognize, through base-pairing, a particular codon or subset of codons in mRNA. The intricate chemistry that enables these tRNAs to translate a specific sequence of A, C, G, and U nucleotides in an mRNA molecule into a specific sequence of amino acids in a protein molecule occurs on the ribosome, a large multimolecular machine composed of both protein and ribosomal RNA. All of these processes are described in detail in Chapter 6.


Cell_Biology_Alberts

Cell_Biology_Alberts. DNA molecules as a rule are very large, containing the specifications for thousands of proteins. Special sequences in the DNA serve as punctuation, defining where the information for each protein begins and ends. And individual segments of the long DNA sequence are transcribed into separate mRNA molecules, coding for different proteins. Each such DNA segment represents one gene. A complication is that RNA molecules transcribed from the same DNA segment can often be processed in more than one way, so as to give rise to a set of alternative versions of a protein, especially in more complex cells such as those of plants and animals. In addition, some DNA segments—a smaller number—are transcribed into RNA molecules that are not translated but have catalytic, regulatory, or structural functions; such DNA segments also count as genes. A gene therefore is defined as the segment of DNA sequence corresponding to a single protein or set of alternative protein variants or to a single catalytic,


Cell_Biology_Alberts

Cell_Biology_Alberts. such DNA segments also count as genes. A gene therefore is defined as the segment of DNA sequence corresponding to a single protein or set of alternative protein variants or to a single catalytic, regulatory, or structural RNA molecule.


Cell_Biology_Alberts

Cell_Biology_Alberts. In all cells, the expression of individual genes is regulated: instead of manufacturing its full repertoire of possible proteins at full tilt all the time, the cell adjusts the rate of transcription and translation of different genes independently, according to need. Stretches of regulatory DNA are interspersed among the segments that code for protein, and these noncoding regions bind to special protein molecules that control the local rate of transcription. The quantity and organization of the regulatory DNA vary widely from one class of organisms to another, but the basic strategy is universal. In this way, the genome of the cell—that is, the totality of its genetic information as embodied in its complete DNA sequence— dictates not only the nature of the cell’s proteins, but also when and where they are to be made.


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 1–8 Life as an autocatalytic process. (A) The cell as a self-replicating collection of catalysts. (B) Polynucleotides (the nucleic acids dnA and RnA, which are nucleotide polymers) provide the sequence information, while proteins (amino acid polymers) provide most of the catalytic functions that serve—through a complex set of chemical reactions—to bring about the synthesis of more polynucleotides and proteins of the same types. A living cell is a dynamic chemical system, operating far from chemical equilibrium. For a cell to grow or to make a new cell in its own image, it must take in free energy from the environment, as well as raw materials, to drive the necessary synthetic reactions. This consumption of free energy is fundamental to life. When it stops, a cell decays toward chemical equilibrium and soon dies.


Cell_Biology_Alberts

Cell_Biology_Alberts. Genetic information is also fundamental to life, and free energy is required for the propagation of this information. For example, to specify one bit of information—that is, one yes/no choice between two equally probable alternatives— costs a defined amount of free energy that can be calculated. The quantitative relationship involves some deep reasoning and depends on a precise definition of the term “free energy,” as explained in Chapter 2. The basic idea, however, is not difficult to understand intuitively.


Cell_Biology_Alberts

Cell_Biology_Alberts. Picture the molecules in a cell as a swarm of objects endowed with thermal energy, moving around violently at random, buffeted by collisions with one another. To specify genetic information—in the form of a DNA sequence, for example—molecules from this wild crowd must be captured, arranged in a specific order defined by some preexisting template, and linked together in a fixed relationship. The bonds that hold the molecules in their proper places on the template and join them together must be strong enough to resist the disordering effect of thermal motion. The process is driven forward by consumption of free energy, which is needed to ensure that the correct bonds are made, and made robustly. In the simplest case, the molecules can be compared with spring-loaded traps, ready to snap into a more stable, lower-energy attached state when they meet their proper partners; as they snap together into the bonded arrangement, their available stored energy—their free energy—like the energy of


Cell_Biology_Alberts

Cell_Biology_Alberts. a more stable, lower-energy attached state when they meet their proper partners; as they snap together into the bonded arrangement, their available stored energy—their free energy—like the energy of the spring in the trap, is released and dissipated as heat. In a cell, the chemical processes underlying information transfer are more complex, but the same basic principle applies: free energy has to be spent on the creation of order.


Cell_Biology_Alberts

Cell_Biology_Alberts. To replicate its genetic information faithfully, and indeed to make all its complex molecules according to the correct specifications, the cell therefore requires free energy, which has to be imported somehow from the surroundings. As we shall see in Chapter 2, the free energy required by animal cells is derived from chemical bonds in food molecules that the animals eat, while plants get their free energy from sunlight. All cells Function as Biochemical Factories dealing with the same Basic molecular Building Blocks


Cell_Biology_Alberts

Cell_Biology_Alberts. All cells Function as Biochemical Factories dealing with the same Basic molecular Building Blocks Because all cells make DNA, RNA, and protein, all cells have to contain and manipulate a similar collection of small molecules, including simple sugars, nucleotides, and amino acids, as well as other substances that are universally required. All cells, for example, require the phosphorylated nucleotide ATP (adenosine triphosphate), not only as a building block for the synthesis of DNA and RNA, but also as a carrier of the free energy that is needed to drive a huge number of chemical reactions in the cell.


Cell_Biology_Alberts

Cell_Biology_Alberts. Although all cells function as biochemical factories of a broadly similar type, many of the details of their small-molecule transactions differ. Some organisms, such as plants, require only the simplest of nutrients and harness the energy of sunlight to make all their own small organic molecules. Other organisms, such as animals, feed on living things and must obtain many of their organic molecules ready-made. We return to this point later. Another universal feature is that each cell is enclosed by a membrane—the plasma membrane. This container acts as a selective barrier that enables the cell to concentrate nutrients gathered from its environment and retain the products it


Cell_Biology_Alberts

Cell_Biology_Alberts. Figure 1–9 Formation of a membrane by amphiphilic phospholipid molecules. Phospholipids have a hydrophilic (water-loving, phosphate) head group and a hydrophobic (water-avoiding, hydrocarbon) tail. At an interface between oil and water, they arrange themselves as a single sheet with their head groups facing the water and their tail groups facing the oil. But when immersed in water, they aggregate to form bilayers enclosing aqueous compartments, as indicated. synthesizes for its own use, while excreting its waste products. Without a plasma membrane, the cell could not maintain its integrity as a coordinated chemical system.


Cell_Biology_Alberts

Cell_Biology_Alberts. The molecules that form a membrane have the simple physicochemical property of being amphiphilic—that is, consisting of one part that is hydrophobic (water-insoluble) and another part that is hydrophilic (water-soluble). Such molecules placed in water aggregate spontaneously, arranging their hydrophobic portions to be as much in contact with one another as possible to hide them from the water, while keeping their hydrophilic portions exposed. Amphiphilic molecules of appropriate shape, such as the phospholipid molecules that comprise most of the plasma membrane, spontaneously aggregate in water to create a bilayer that forms small closed vesicles (Figure 1–9). The phenomenon can be demonstrated in a test tube by simply mixing phospholipids and water together; under appropriate conditions, small vesicles form whose aqueous contents are isolated from the external medium.


Cell_Biology_Alberts

Cell_Biology_Alberts. Although the chemical details vary, the hydrophobic tails of the predominant membrane molecules in all cells are hydrocarbon polymers (–CH2–CH2–CH2–), and their spontaneous assembly into a bilayered vesicle is but one of many examples of an important general principle: cells produce molecules whose chemical properties cause them to self-assemble into the structures that a cell needs.


Cell_Biology_Alberts

Cell_Biology_Alberts. The cell boundary cannot be totally impermeable. If a cell is to grow and reproduce, it must be able to import raw materials and export waste across its plasma membrane. All cells therefore have specialized proteins embedded in their membrane that transport specific molecules from one side to the other. Some of these membrane transport proteins, like some of the proteins that catalyze the fundamental small-molecule reactions inside the cell, have been so well preserved over the course of evolution that we can recognize the family resemblances between them in comparisons of even the most distantly related groups of living organisms.


Cell_Biology_Alberts

Cell_Biology_Alberts. The transport proteins in the membrane largely determine which molecules enter the cell, and the catalytic proteins inside the cell determine the reactions that those molecules undergo. Thus, by specifying the proteins that the cell is to manufacture, the genetic information recorded in the DNA sequence dictates the entire chemistry of the cell; and not only its chemistry, but also its form and its behavior, for these too are chiefly constructed and controlled by the cell’s proteins. A living cell can exist with Fewer Than 500 Genes


Cell_Biology_Alberts

Cell_Biology_Alberts. A living cell can exist with Fewer Than 500 Genes The basic principles of biological information transfer are simple enough, but how complex are real living cells? In particular, what are the minimum requirements? We can get a rough indication by considering a species that has one of the smallest known genomes—the bacterium Mycoplasma genitalium (Figure 1–10). This organism lives as a parasite in mammals, and its environment provides it with many of its small molecules ready-made. Nevertheless, it still has to make all the large molecules—DNA, RNAs, and proteins—required for the basic processes of heredity. It has about 530 genes, about 400 of which are essential. Its genome of 580,070 nucleotide pairs represents 145,018 bytes of information—about as much as it takes to record the text of one chapter of this book. Cell biology may be complicated, but it is not impossibly so.


Cell_Biology_Alberts

Cell_Biology_Alberts. The minimum number of genes for a viable cell in today’s environments is probably not less than 300, although there are only about 60 genes in the core set that is shared by all living species.


Cell_Biology_Alberts

Cell_Biology_Alberts. The individual cell is the minimal self-reproducing unit of living matter, and it consists of a self-replicating collection of catalysts. Central to this reproduction is the transmission of genetic information to progeny cells. Every cell on our planet stores its genetic information in the same chemical form—as double-stranded DNA. The cell replicates its information by separating the paired DNA strands and using each as a template for polymerization to make a new DNA strand with a complementary sequence of nucleotides. The same strategy of templated polymerization is used to transcribe portions of the information from DNA into molecules of the closely related polymer, RNA. These RNA molecules in turn guide the synthesis of protein molecules by the more complex machinery of translation, involving a large multi-molecular machine, the ribosome. Proteins are the principal catalysts for almost all the chemical reactions in the cell; their other functions include the selective import and


Cell_Biology_Alberts

Cell_Biology_Alberts. involving a large multi-molecular machine, the ribosome. Proteins are the principal catalysts for almost all the chemical reactions in the cell; their other functions include the selective import and export of small molecules across the plasma membrane that forms the cell’s boundary. The specific function of each protein depends on its amino acid sequence, which is specified by the nucleotide sequence of a corresponding segment of the DNA—the gene that codes for that protein. In this way, the genome of the cell determines its chemistry; and the chemistry of every living cell is fundamentally similar, because it must provide for the synthesis of DNA, RNA, and protein. The simplest known cells can survive with about 400 genes.


Cell_Biology_Alberts

Cell_Biology_Alberts. The dIveRsITy oF Genomes And The TRee oF lIFe The success of living organisms based on DNA, RNA, and protein has been spectacular. Life has populated the oceans, covered the land, infiltrated the Earth’s crust, and molded the surface of our planet. Our oxygen-rich atmosphere, the deposits of coal and oil, the layers of iron ores, the cliffs of chalk and limestone and marble—all these are products, directly or indirectly, of past biological activity on Earth.


Cell_Biology_Alberts

Cell_Biology_Alberts. Living things are not confined to the familiar temperate realm of land, water, and sunlight inhabited by plants and plant-eating animals. They can be found in the darkest depths of the ocean, in hot volcanic mud, in pools beneath the frozen surface of the Antarctic, and buried kilometers deep in the Earth’s crust. The creatures that live in these extreme environments are generally unfamiliar, not only because they are inaccessible, but also because they are mostly microscopic. In more homely habitats, too, most organisms are too small for us to see without special equipment: they tend to go unnoticed, unless they cause a disease or rot the timbers of our houses. Yet microorganisms make up most of the total mass of living matter on our planet. Only recently, through new methods of molecular analysis and specifically through the analysis of DNA sequences, have we begun to get a picture of life on Earth that is not grossly distorted by our biased perspective as large animals living on


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Cell_Biology_Alberts. analysis and specifically through the analysis of DNA sequences, have we begun to get a picture of life on Earth that is not grossly distorted by our biased perspective as large animals living on dry land.


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Cell_Biology_Alberts. In this section, we consider the diversity of organisms and the relationships among them. Because the genetic information for every organism is written in the universal language of DNA sequences, and the DNA sequence of any given organism can be readily obtained by standard biochemical techniques, it is now possible to characterize, catalog, and compare any set of living organisms with reference to these sequences. From such comparisons we can estimate the place of each organism in the family tree of living species—the “tree of life.” But before describing what this approach reveals, we need first to consider the routes by which cells in different environments obtain the matter and energy they require to survive and proliferate, and the ways in which some classes of organisms depend on others for their basic chemical needs. cells can Be Powered by a variety of Free-energy sources


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Cell_Biology_Alberts. cells can Be Powered by a variety of Free-energy sources Living organisms obtain their free energy in different ways. Some, such as animals, fungi, and the many different bacteria that live in the human gut, get it by feeding on other living things or the organic chemicals they produce; such organisms 0.2 µm Figure 1–10 Mycoplasma genitalium. scanning electron micrograph showing the irregular shape of this small bacterium, reflecting the lack of any rigid cell wall.


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Cell_Biology_Alberts. Figure 1–10 Mycoplasma genitalium. scanning electron micrograph showing the irregular shape of this small bacterium, reflecting the lack of any rigid cell wall. cross section (transmission electron micrograph) of a Mycoplasma cell. of the 530 genes of Mycoplasma genitalium, 43 code for transfer, ribosomal, and other non-messenger RnAs. Functions are known, or can be guessed, for 339 of the genes coding for protein: of these, 154 are involved in replication, transcription, translation, and related processes involving dnA, RnA, and protein; 98 in the membrane and surface structures of the cell; 46 in the transport of nutrients and other molecules across the membrane; 71 in energy conversion and the synthesis and degradation of small molecules; and 12 in the regulation of cell division and other processes. note that these categories are partly overlapping, so that some genes feature twice. (A, from s.


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Cell_Biology_Alberts. Razin et al., Infect. Immun. 30:538–546, 1980. With permission from the American society for microbiology; B, courtesy of Roger cole, in medical microbiology, 4th ed. [s. Baron ed.]. Galveston: university of Texas medical Branch, 1996.) are called organotrophic (from the Greek word trophe, meaning “food”). Others derive their energy directly from the nonliving world. These primary energy converters fall into two classes: those that harvest the energy of sunlight, and those that capture their energy from energy-rich systems of inorganic chemicals in the environment (chemical systems that are far from chemical equilibrium). Organisms of the former class are called phototrophic (feeding on sunlight); those of the latter are called lithotrophic (feeding on rock). Organotrophic organisms could not exist without these primary energy converters, which are the most plentiful form of life.


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Cell_Biology_Alberts. Phototrophic organisms include many types of bacteria, as well as algae and plants, on which we—and virtually all the living things that we ordinarily see around us—depend. Phototrophic organisms have changed the whole chemistry of our environment: the oxygen in the Earth’s atmosphere is a by-product of their biosynthetic activities. Lithotrophic organisms are not such an obvious feature of our world, because they are microscopic and mostly live in habitats that humans do not frequent— deep in the ocean, buried in the Earth’s crust, or in various other inhospitable environments. But they are a major part of the living world, and they are especially important in any consideration of the history of life on Earth.


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Cell_Biology_Alberts. Some lithotrophs get energy from aerobic reactions, which use molecular oxygen from the environment; since atmospheric O2 is ultimately the product of living organisms, these aerobic lithotrophs are, in a sense, feeding on the products of past life. There are, however, other lithotrophs that live anaerobically, in places where little or no molecular oxygen is present. These are circumstances similar to those that existed in the early days of life on Earth, before oxygen had accumulated. The most dramatic of these sites are the hot hydrothermal vents on the floor of the Pacific and Atlantic Oceans. They are located where the ocean floor is spreading as new portions of the Earth’s crust form by a gradual upwelling of material from the Earth’s interior (Figure 1–11). Downward-percolating seawater is heated and driven back upward as a submarine geyser, carrying with it a current of chemicals from the hot rocks below. A typical cocktail might include H2S, H2, CO,


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Cell_Biology_Alberts. Mn2+, Fe2+, Ni2+, CH2, NH4 , and phosphorus-containing compounds. A dense SEA dark cloud of hot, mineral-rich water 350°C percolation contour of seawater Figure 1–11 The geology of a hot hydrothermal vent in the ocean floor. As indicated, water percolates down toward the hot molten rock upwelling from the earth’s interior and is heated and driven back upward, carrying minerals leached from the hot rock. A temperature gradient is set up, from more than 350°c near the core of the vent, down to 2–3°c in the surrounding ocean. minerals precipitate from the water as it cools, forming a chimney. different classes of organisms, thriving at different temperatures, live in different neighborhoods of the chimney. A typical chimney might be a few meters tall, spewing out hot, mineral-rich water at a flow rate of 1–2 m/sec.


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Cell_Biology_Alberts. multicellular animals, e.g., tube worms population of microbes lives in the neighborhood of the vent, thriving on this austere diet and harvesting free energy from reactions between the available chemicals. Other organisms—clams, mussels, and giant marine worms—in turn live off the microbes at the vent, forming an entire ecosystem analogous to the world of plants and animals that we belong to, but powered by geochemical energy instead of light (Figure 1–12).


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Cell_Biology_Alberts. To make a living cell requires matter, as well as free energy. DNA, RNA, and protein are composed of just six elements: hydrogen, carbon, nitrogen, oxygen, sulfur, and phosphorus. These are all plentiful in the nonliving environment, in the Earth’s rocks, water, and atmosphere. But they are not present in chemical forms that allow easy incorporation into biological molecules. Atmospheric N2 and CO2, in particular, are extremely unreactive. A large amount of free energy is required to drive the reactions that use these inorganic molecules to make the organic compounds needed for further biosynthesis—that is, to fix nitrogen and carbon dioxide, so as to make N and C available to living organisms. Many types of living cells lack the biochemical machinery to achieve this fixation; they instead rely on other classes of cells to do the job for them. We animals depend on plants for our supplies of organic carbon and nitrogen compounds. Plants in turn, although they can fix carbon dioxide


Cell_Biology_Alberts

Cell_Biology_Alberts. rely on other classes of cells to do the job for them. We animals depend on plants for our supplies of organic carbon and nitrogen compounds. Plants in turn, although they can fix carbon dioxide from the atmosphere, lack the ability to fix atmospheric nitrogen; they depend in part on nitrogen-fixing bacteria to supply their need for nitrogen compounds. Plants of the pea family, for example, harbor symbiotic nitrogen-fixing bacteria in nodules in their roots.


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Cell_Biology_Alberts. Living cells therefore differ widely in some of the most basic aspects of their biochemistry. Not surprisingly, cells with complementary needs and capabilities have developed close associations. Some of these associations, as we see below, have evolved to the point where the partners have lost their separate identities altogether: they have joined forces to form a single composite cell. The Greatest Biochemical diversity exists Among Prokaryotic cells From simple microscopy, it has long been clear that living organisms can be classified on the basis of cell structure into two groups: the eukaryotes and the


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Cell_Biology_Alberts. Figure 1–12 Organisms living at a depth of 2500 meters near a vent in the ocean floor. close to the vent, at temperatures up to about 120°c, various lithotrophic species of bacteria and archaea (archaebacteria) live, directly fueled by geochemical energy. A little further away, where the temperature is lower, various invertebrate animals live by feeding on these microorganisms. most remarkable are these giant (2 meter) tube worms, Riftia pachyptila, which, rather than feed on the lithotrophic cells, live in symbiosis with them: specialized organs in the worms harbor huge numbers of symbiotic sulfur-oxidizing bacteria. These bacteria harness geochemical energy and supply nourishment to their hosts, which have no mouth, gut, or anus. The tube worms are thought to have evolved from more conventional animals, and to have become secondarily adapted to life at hydrothermal vents. (courtesy of monika Bright, university of vienna, Austria.) rod-shaped cells the smallest cells e.g.,


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Cell_Biology_Alberts. more conventional animals, and to have become secondarily adapted to life at hydrothermal vents. (courtesy of monika Bright, university of vienna, Austria.) rod-shaped cells the smallest cells e.g., Escherichia coli, e.g., Mycoplasma, Vibrio cholerae Spiroplasma prokaryotes. Eukaryotes keep their DNA in a distinct membrane-enclosed intracellular compartment called the nucleus. (The name is from the Greek, meaning “truly nucleated,” from the words eu, “well” or “truly,” and karyon, “kernel” or “nucleus.”) Prokaryotes have no distinct nuclear compartment to house their DNA. Plants, fungi, and animals are eukaryotes; bacteria are prokaryotes, as are archaea—a separate class of prokaryotic cells, discussed below.


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Cell_Biology_Alberts. Most prokaryotic cells are small and simple in outward appearance (Figure 1–13), and they live mostly as independent individuals or in loosely organized communities, rather than as multicellular organisms. They are typically spherical or rod-shaped and measure a few micrometers in linear dimension. They often have a tough protective coat, called a cell wall, beneath which a plasma membrane encloses a single cytoplasmic compartment containing DNA, RNA, proteins, and the many small molecules needed for life. In the electron microscope, this cell interior appears as a matrix of varying texture without any discernible organized internal structure (Figure 1–14).


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Cell_Biology_Alberts. Prokaryotic cells live in an enormous variety of ecological niches, and they are astonishingly varied in their biochemical capabilities—far more so than eukaryotic cells. Organotrophic species can utilize virtually any type of organic molecule as food, from sugars and amino acids to hydrocarbons and methane gas. Photo-trophic species (Figure 1–15) harvest light energy in a variety of ways, some of them generating oxygen as a by-product, others not. Lithotrophic species can feed on a plain diet of inorganic nutrients, getting their carbon from CO2, and relying on H2S to fuel their energy needs (Figure 1–16)—or on H2, or Fe2+, or elemental sulfur, or any of a host of other chemicals that occur in the environment.


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Cell_Biology_Alberts. Figure 1–14 The structure of a bacterium. (A) The bacterium Vibrio cholerae, showing its simple internal organization. like many other species, Vibrio has a helical appendage at one end—a flagellum—that rotates as a propeller to drive the cell forward. It can infect the human small intestine to cause cholera; the severe diarrhea that accompanies this disease kills more than 100,000 people a year. (B) An electron micrograph of a longitudinal section through the widely studied bacterium Escherichia coli (E. coli). The cell’s dnA is concentrated in the lightly stained region. Part of our normal intestinal flora, E. coli is related to Vibrio, and it has many flagella distributed over its surface that are not visible in this section. (B, courtesy of e. kellenberger.) spherical cells e.g., Streptococcus spiral cells e.g., Treponema pallidum


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Cell_Biology_Alberts. Figure 1–13 Shapes and sizes of some bacteria. Although most are small, as shown, measuring a few micrometers in linear dimension, there are also some giant species. An extreme example (not shown) is the cigar-shaped bacterium Epulopiscium fishelsoni, which lives in the gut of a surgeonfish and can be up to 600 μm long. Much of this world of microscopic organisms is virtually unexplored. Traditional methods of bacteriology have given us an acquaintance with those species that can be isolated and cultured in the laboratory. But DNA sequence analysis of the populations of bacteria and archaea in samples from natural habitats—such as soil or ocean water, or even the human mouth—has opened our eyes to the fact that most species cannot be cultured by standard laboratory techniques. According to one estimate, at least 99% of prokaryotic species remain to be characterized. Detected only by their DNA, it has not yet been possible to grow the vast majority of them in laboratories.


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Cell_Biology_Alberts. The Tree of life has Three Primary Branches: Bacteria, Archaea, and eukaryotes The classification of living things has traditionally depended on comparisons of their outward appearances: we can see that a fish has eyes, jaws, backbone, brain, and so on, just as we do, and that a worm does not; that a rosebush is cousin to an apple tree, but is less similar to a grass. As Darwin showed, we can readily interpret such close family resemblances in terms of evolution from common ancestors, and we can find the remains of many of these ancestors preserved in the fossil record. In this way, it has been possible to begin to draw a family tree of living organisms, showing the various lines of descent, as well as branch points in the history, where the ancestors of one group of species became different from those of another.


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Cell_Biology_Alberts. When the disparities between organisms become very great, however, these methods begin to fail. How do we decide whether a fungus is closer kin to a plant or to an animal? When it comes to prokaryotes, the task becomes harder still: one microscopic rod or sphere looks much like another. Microbiologists have therefore sought to classify prokaryotes in terms of their biochemistry and nutritional requirements. But this approach also has its pitfalls. Amid the bewildering variety of biochemical behaviors, it is difficult to know which differences truly reflect differences of evolutionary history.


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Cell_Biology_Alberts. Genome analysis has now given us a simpler, more direct, and much more powerful way to determine evolutionary relationships. The complete DNA sequence of an organism defines its nature with almost perfect precision and in exhaustive detail. Moreover, this specification is in a digital form—a string of let-ters—that can be entered straightforwardly into a computer and compared with the corresponding information for any other living thing. Because DNA is subject to random changes that accumulate over long periods of time (as we shall see shortly), the number of differences between the DNA sequences of two organisms can provide a direct, objective, quantitative indication of the evolutionary distance between them.


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Cell_Biology_Alberts. This approach has shown that the organisms that were traditionally classed together as “bacteria” can be as widely divergent in their evolutionary origins as is any prokaryote from any eukaryote. It is now clear that the prokaryotes comprise two distinct groups that diverged early in the history of life on Earth, before the eukaryotes diverged as a separate group. The two groups of prokaryotes are called the bacteria (or eubacteria) and the archaea (or archaebacteria). Detailed genome analyses have recently revealed that the first eukayotic cell formed after a Figure 1–15 The phototrophic bacterium Anabaena cylindrica viewed in the light microscope. The cells of this species form long, multicellular filaments. most of the cells (labeled v) perform photosynthesis, while others become specialized for nitrogen fixation (labeled h) or develop into resistant spores (labeled s). (courtesy of dave G. Adams.) Figure 1–16 A lithotrophic bacterium.


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Cell_Biology_Alberts. Figure 1–16 A lithotrophic bacterium. Beggiatoa, which lives in sulfurous environments, gets its energy by oxidizing h2s and can fix carbon even in the dark. note the yellow deposits of sulfur inside the cells. (courtesy of Ralph W. Wolfe.) ARCHAEA BACTERIA EUKARYOTES common ancestor cellAquifex Thermotoga cyanobacteria Bacillus E. coli Aeropyrum Sulfolobus Haloferax Methano-thermobacter Methanococcus Paramecium Dictyostelium Euglena Trypanosoma maize yeast human 1 change/10 nucleotides frst eukaryote Giardia Trichomonas particular type of ancient archaeal cell engulfed an ancient bacterium (see Figure 12–3). Thus, the living world today is considered to consist of three major divisions or domains: bacteria, archaea, and eukaryotes (Figure 1–17).


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Cell_Biology_Alberts. Archaea are often found inhabiting environments that we humans avoid, such as bogs, sewage treatment plants, ocean depths, salt brines, and hot acid springs, although they are also widespread in less extreme and more homely environments, from soils and lakes to the stomachs of cattle. In outward appearance they are not easily distinguished from bacteria. At a molecular level, archaea seem to resemble eukaryotes more closely in their machinery for handling genetic information (replication, transcription, and translation), but bacteria more closely in their apparatus for metabolism and energy conversion. We discuss below how this might be explained.


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Cell_Biology_Alberts. Both in the storage and in the copying of genetic information, random accidents and errors occur, altering the nucleotide sequence—that is, creating mutations. Therefore, when a cell divides, its two daughters are often not quite identical to one another or to their parent. On rare occasions, the error may represent a change for the better; more probably, it will cause no significant difference in the cell’s prospects. But in many cases, the error will cause serious damage—for example, by disrupting the coding sequence for a key protein. Changes due to mistakes of the first type will tend to be perpetuated, because the altered cell has an increased likelihood of reproducing itself. Changes due to mistakes of the second type—selectively neutral changes—may be perpetuated or not: in the competition for limited resources, it is a matter of chance whether the altered cell or its cousins will succeed. But changes that cause serious damage lead nowhere: the cell that suffers them dies,


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Cell_Biology_Alberts. competition for limited resources, it is a matter of chance whether the altered cell or its cousins will succeed. But changes that cause serious damage lead nowhere: the cell that suffers them dies, leaving no progeny. Through endless repetition of this cycle of error and trial—of mutation and natural selection—organisms evolve: their genetic specifications change, giving them new ways to exploit the environment more effectively, to survive in competition with others, and to reproduce successfully.


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Cell_Biology_Alberts. Some parts of the genome will change more easily than others in the course of evolution. A segment of DNA that does not code for protein and has no significant regulatory role is free to change at a rate limited only by the frequency of random errors. In contrast, a gene that codes for a highly optimized essential protein or RNA molecule cannot alter so easily: when mistakes occur, the faulty cells are almost always eliminated. Genes of this latter sort are therefore highly conserved. Through 3.5 billion years or more of evolutionary history, many features of the genome have changed beyond all recognition, but the most highly conserved genes remain perfectly recognizable in all living species.


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Cell_Biology_Alberts. Figure 1–17 The three major divisions (domains) of the living world. note that the word bacteria was originally used to refer to prokaryotes in general, but more recently has been redefined to refer to eubacteria specifically. The tree shown here is based on comparisons of the nucleotide sequence of a ribosomal RnA (rRnA) subunit in the different species, and the distances in the diagram represent estimates of the numbers of evolutionary changes that have occurred in this molecule in each lineage (see Figure 1–18). The parts of the tree shrouded in gray cloud represent uncertainties about details of the true pattern of species divergence in the course of evolution: comparisons of nucleotide or amino acid sequences of molecules other than rRnA, as well as other arguments, can lead to somewhat different trees. As indicated, the nucleus of the eukaryotic cell is now thought to have emerged from a sub-branch within the archaea, so that in the beginning the tree of life had only two


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Cell_Biology_Alberts. somewhat different trees. As indicated, the nucleus of the eukaryotic cell is now thought to have emerged from a sub-branch within the archaea, so that in the beginning the tree of life had only two branches—bacteria and archaea.


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Cell_Biology_Alberts. GTTCCGGGGGGAGTATGGTTGCAAAGCTGAAACTTAAAGGAATTGACGGAAGGGCACCACCAGGAGTGGAGCCTGCGGCTTAATTTGACTCAACACGGGAAACCTCACCC human GCCGCCTGGGGAGTACGGTCGCAAGACTGAAACTTAAAGGAATTGGCGGGGGAGCACTACAACGGGTGGAGCCTGCGGTTTAATTGGATTCAACGCCGGGCATCTTACCA Methanococcus ACCGCCTGGGGAGTACGGCCGCAAGGTTAAAACTCAAATGAATTGACGGGGGCCCGC.ACAAGCGGTGGAGCATGTGGTTTAATTCGATGCAACGCGAAGAACCTTACCT E. coli GTTCCGGGGGGAGTATGGTTGCAAAGCTGAAACTTAAAGGAATTGACGGAAGGGCACCACCAGGAGTGGAGCCTGCGGCTTAATTTGACTCAACACGGGAAACCTCACCC human


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Cell_Biology_Alberts. These latter genes are the ones we must examine if we wish to trace family relationships between the most distantly related organisms in the tree of life. The initial studies that led to the classification of the living world into the three domains of bacteria, archaea, and eukaryotes were based chiefly on analysis of one of the rRNA components of the ribosome. Because the translation of RNA into protein is fundamental to all living cells, this component of the ribosome has been very well conserved since early in the history of life on Earth (Figure 1–18). Natural selection has generally favored those prokaryotic cells that can reproduce the fastest by taking up raw materials from their environment and replicating themselves most efficiently, at the maximal rate permitted by the available food supplies. Small size implies a large ratio of surface area to volume, thereby helping to maximize the uptake of nutrients across the plasma membrane and boosting a cell’s reproductive rate.


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Cell_Biology_Alberts. Presumably for these reasons, most prokaryotic cells carry very little superfluous baggage; their genomes are small, with genes packed closely together and minimal quantities of regulatory DNA between them. The small genome size has made it easy to use modern DNA sequencing techniques to determine complete genome sequences. We now have this information for thousands of species of bacteria and archaea, as well as for hundreds of species of eukaryotes. Most bacterial and archaeal genomes contain between 106 and 107 nucleotide pairs, encoding 1000–6000 genes.


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Cell_Biology_Alberts. A complete DNA sequence reveals both the genes an organism possesses and the genes it lacks. When we compare the three domains of the living world, we can begin to see which genes are common to all of them and must therefore have been present in the cell that was ancestral to all present-day living things, and which genes are peculiar to a single branch in the tree of life. To explain the findings, however, we need to consider a little more closely how new genes arise and genomes evolve. The raw material of evolution is the DNA sequence that already exists: there is no natural mechanism for making long stretches of new random sequence. In this sense, no gene is ever entirely new. Innovation can, however, occur in several ways (Figure 1–19): 1. Intragenic mutation: an existing gene can be randomly modified by changes in its DNA sequence, through various types of error that occur mainly in the process of DNA replication. 2.


Cell_Biology_Alberts

Cell_Biology_Alberts. Intragenic mutation: an existing gene can be randomly modified by changes in its DNA sequence, through various types of error that occur mainly in the process of DNA replication. 2. Gene duplication: an existing gene can be accidentally duplicated so as to create a pair of initially identical genes within a single cell; these two genes may then diverge in the course of evolution. 3. DNA segment shuffling: two or more existing genes can break and rejoin to make a hybrid gene consisting of DNA segments that originally belonged to separate genes. 4. Horizontal (intercellular) transfer: a piece of DNA can be transferred from the genome of one cell to that of another—even to that of another species. This process is in contrast with the usual vertical transfer of genetic information from parent to progeny. Each of these types of change leaves a characteristic trace in the DNA sequence of the organism, and there is clear evidence that all four processes have frequently


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Cell_Biology_Alberts. Each of these types of change leaves a characteristic trace in the DNA sequence of the organism, and there is clear evidence that all four processes have frequently Figure 1–18 Genetic information conserved since the days of the last common ancestor of all living things.


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Cell_Biology_Alberts. Figure 1–18 Genetic information conserved since the days of the last common ancestor of all living things. A part of the gene for the smaller of the two main rRnA components of the ribosome is shown. (The complete molecule is about 1500–1900 nucleotides long, depending on species.) corresponding segments of nucleotide sequence from an archaean (Methanococcus jannaschii), a bacterium (Escherichia coli), and a eukaryote (Homo sapiens) are aligned. sites where the nucleotides are identical between species are indicated by a vertical line; the human sequence is repeated at the bottom of the alignment so that all three two-way comparisons can be seen. A dot halfway along the E. coli sequence denotes a site where a nucleotide has been either deleted from the bacterial lineage in the course of evolution or inserted in the other two lineages. note that the sequences from these three organisms, representative of the three domains of the living world, still retain unmistakable similarities.


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Cell_Biology_Alberts. occurred. In later chapters, we discuss the underlying mechanisms, but for the present we focus on the consequences. Gene duplications Give Rise to Families of Related Genes Within a single cell


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Cell_Biology_Alberts. Gene duplications Give Rise to Families of Related Genes Within a single cell A cell duplicates its entire genome each time it divides into two daughter cells. However, accidents occasionally result in the inappropriate duplication of just part of the genome, with retention of original and duplicate segments in a single cell. Once a gene has been duplicated in this way, one of the two gene copies is free to mutate and become specialized to perform a different function within the same cell. Repeated rounds of this process of duplication and divergence, over many millions of years, have enabled one gene to give rise to a family of genes that may all be found within a single genome. Analysis of the DNA sequence of prokaryotic genomes reveals many examples of such gene families: in the bacterium Bacillus subtilis, for example, 47% of the genes have one or more obvious relatives (Figure 1–20).


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Cell_Biology_Alberts. When genes duplicate and diverge in this way, the individuals of one species become endowed with multiple variants of a primordial gene. This evolutionary process has to be distinguished from the genetic divergence that occurs when one species of organism splits into two separate lines of descent at a branch point in the family tree—when the human line of descent became separate from that of chimpanzees, for example. There, the genes gradually become different in the course of evolution, but they are likely to continue to have corresponding functions in the two sister species. Genes that are related by descent in this way—that is, genes in two separate species that derive from the same ancestral gene in the last common ancestor of those two species—are called orthologs. Related genes that have resulted from a gene duplication event within a single genome—and


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Cell_Biology_Alberts. Figure 1–19 Four modes of genetic innovation and their effects on the DNA sequence of an organism. A special form of horizontal transfer occurs when two different types of cells enter into a permanent symbiotic association. Genes from one of the cells then may be transferred to the genome of the other, as we shall see below when we discuss mitochondria and chloroplasts. 283 genes in families with 38–77 gene members 764 genes in families with 4–19 gene members 2126 genes with no family relationship273 genes in families with 3 gene members 568 genes in families with 2 gene members are likely to have diverged in their function—are called paralogs. Genes that are related by descent in either way are called homologs, a general term used to cover both types of relationship (Figure 1–21). Genes can Be Transferred Between organisms, Both in the laboratory and in nature


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Cell_Biology_Alberts. Prokaryotes provide good examples of the horizontal transfer of genes from one species of cell to another. The most obvious tell-tale signs are sequences recognizable as being derived from viruses, those infecting bacteria being called bacteriophages (Figure 1–22). Viruses are small packets of genetic material that have evolved as parasites on the reproductive and biosynthetic machinery of host cells. Although not themselves living cells, they often serve as vectors for gene transfer. A virus will replicate in one cell, emerge from it with a protective wrapping, and then enter and infect another cell, which may be of the same or a different species. Often, the infected cell will be killed by the massive proliferation of virus particles inside it; but sometimes, the viral DNA, instead of directly generating these particles, may persist in its host for many cell generations as a relatively innocuous passenger, either as a separate intracellular fragment of DNA, known as a plasmid, or as


Cell_Biology_Alberts

Cell_Biology_Alberts. generating these particles, may persist in its host for many cell generations as a relatively innocuous passenger, either as a separate intracellular fragment of DNA, known as a plasmid, or as a sequence inserted into the cell’s regular genome. In their travels, viruses can accidentally pick up fragments of DNA from the genome of one host cell and ferry them into another cell. Such transfers of genetic material are very common in prokaryotes.


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Cell_Biology_Alberts. Horizontal transfers of genes between eukaryotic cells of different species are very rare, and they do not seem to have played a significant part in eukaryote evolution (although massive transfers from bacterial to eukaryotic genomes have occurred in the evolution of mitochondria and chloroplasts, as we discuss below). genes GA and GB are orthologs genes G1 and G2 are paralogs Figure 1–20 Families of evolutionarily related genes in the genome of Bacillus subtilis. The largest gene family in this bacterium consists of 77 genes coding for varieties of ABc transporters—a class of membrane transport proteins found in all three domains of the living world. (Adapted from F. kunst et al., Nature 390:249–256, 1997. With permission from macmillan Publishers ltd.) Figure 1–21 Paralogous genes and orthologous genes: two types of gene homology based on different evolutionary pathways. (A) orthologs. (B) Paralogs.


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Cell_Biology_Alberts. In contrast, horizontal gene transfers occur much more frequently between different species of prokaryotes. Many prokaryotes have a remarkable capacity to take up even nonviral DNA molecules from their surroundings and thereby capture the genetic information these molecules carry. By this route, or by virus-mediated transfer, bacteria and archaea in the wild can acquire genes from neighboring cells relatively easily. Genes that confer resistance to an antibiotic or an ability to produce a toxin, for example, can be transferred from species to species and provide the recipient bacterium with a selective advantage. In this way, new and sometimes dangerous strains of bacteria have been observed to evolve in the bacterial ecosystems that inhabit hospitals or the various niches in the human body. For example, horizontal gene transfer is responsible for the spread, over the past 40 years, of penicillin-resistant strains of Neisseria gonorrhoeae, the bacterium that causes gonorrhea. On a


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Cell_Biology_Alberts. body. For example, horizontal gene transfer is responsible for the spread, over the past 40 years, of penicillin-resistant strains of Neisseria gonorrhoeae, the bacterium that causes gonorrhea. On a longer time scale, the results can be even more profound; it has been estimated that at least 18% of all of the genes in the present-day genome of E. coli have been acquired by horizontal transfer from another species within the past 100 million years.


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Cell_Biology_Alberts. sex Results in horizontal exchanges of Genetic Information Within a species Horizontal gene transfer among prokaryotes has a parallel in a phenomenon familiar to us all: sex. In addition to the usual vertical transfer of genetic material from parent to offspring, sexual reproduction causes a large-scale horizontal transfer of genetic information between two initially separate cell lineages—those of the father and the mother. A key feature of sex, of course, is that the genetic exchange normally occurs only between individuals of the same species. But no matter whether they occur within a species or between species, horizontal gene Figure 1–22 The viral transfer of DNA into a cell. (A) An electron micrograph of particles of a bacterial virus, the T4 bacteriophage. The head of this virus contains the viral dnA; the tail contains the apparatus for injecting the dnA into a host bacterium. (B) A cross section of an


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Cell_Biology_Alberts. E. coli bacterium with a T4 bacteriophage latched onto its surface. The large dark objects inside the bacterium are the heads of new T4 particles in the course of assembly. When they are mature, the bacterium will burst open to release them. (c–e) The process of dnA injection into the bacterium, as visualized in unstained, frozen samples by cryoelectron microscopy. (c) Attachment begins. Attached state during dnA injection.


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Cell_Biology_Alberts. Attached state during dnA injection. virus head has emptied all of its dnA into the bacterium. (A, courtesy of James Paulson; B, courtesy of Jonathan king and erika hartwig from G. karp, cell and molecular Biology, 2nd ed. new york: John Wiley & sons, 1999. With permission from John Wiley & sons; c–e, courtesy of Ian molineux, university of Texas at Austin and Jun liu, university of Texas health science center, houston.) transfers leave a characteristic imprint: they result in individuals who are related more closely to one set of relatives with respect to some genes, and more closely to another set of relatives with respect to others. By comparing the DNA sequences of individual human genomes, an intelligent visitor from outer space could deduce that humans reproduce sexually, even if it knew nothing about human behavior.


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Cell_Biology_Alberts. Sexual reproduction is widespread (although not universal), especially among eukaryotes. Even bacteria indulge from time to time in controlled sexual exchanges of DNA with other members of their own species. Natural selection has clearly favored organisms that can reproduce sexually, although evolutionary theorists dispute precisely what that selective advantage is. The Function of a Gene can often Be deduced from Its sequence


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Cell_Biology_Alberts. The Function of a Gene can often Be deduced from Its sequence Family relationships among genes are important not just for their historical interest, but because they simplify the task of deciphering gene functions. Once the sequence of a newly discovered gene has been determined, a scientist can tap a few keys on a computer to search the entire database of known gene sequences for genes related to it. In many cases, the function of one or more of these homo-logs will have been already determined experimentally. Since gene sequence determines gene function, one can frequently make a good guess at the function of the new gene: it is likely to be similar to that of the already known homologs. In this way, it is possible to decipher a great deal of the biology of an organism simply by analyzing the DNA sequence of its genome and using the information we already have about the functions of genes in other organisms that have been more intensively studied.


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Cell_Biology_Alberts. more Than 200 Gene Families Are common to All Three Primary Branches of the Tree of life


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Cell_Biology_Alberts. Given the complete genome sequences of representative organisms from all three domains—archaea, bacteria, and eukaryotes—we can search systematically for homologies that span this enormous evolutionary divide. In this way we can begin to take stock of the common inheritance of all living things. There are considerable difficulties in this enterprise. For example, individual species have often lost some of the ancestral genes; other genes have almost certainly been acquired by horizontal transfer from another species and therefore are not truly ancestral, even though shared. In fact, genome comparisons strongly suggest that both lineage-specific gene loss and horizontal gene transfer, in some cases between evolutionarily distant species, have been major factors of evolution, at least among prokaryotes. Finally, in the course of 2 or 3 billion years, some genes that were initially shared will have changed beyond recognition through mutation.


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Cell_Biology_Alberts. Because of all these vagaries of the evolutionary process, it seems that only a small proportion of ancestral gene families has been universally retained in a recognizable form. Thus, out of 4873 protein-coding gene families defined by comparing the genomes of 50 species of bacteria, 13 archaea, and 3 unicellular eukaryotes, only 63 are truly ubiquitous (that is, represented in all the genomes analyzed). The great majority of these universal families include components of the translation and transcription systems. This is not likely to be a realistic approximation of an ancestral gene set. A better—though still crude—idea of the latter can be obtained by tallying the gene families that have representatives in multiple, but not necessarily all, species from all three major domains. Such an analysis reveals 264 ancient conserved families. Each family can be assigned a function (at least in terms of general biochemical activity, but usually with more precision). As shown in Table 1–1,


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Cell_Biology_Alberts. an analysis reveals 264 ancient conserved families. Each family can be assigned a function (at least in terms of general biochemical activity, but usually with more precision). As shown in Table 1–1, the largest number of shared gene families are involved in translation and in amino acid metabolism and transport. However, this set of highly conserved gene families represents only a very rough sketch of the common inheritance of all modern life. A more precise reconstruction of the gene complement of the last universal common ancestor will hopefully become feasible with further genome sequencing and more sophisticated forms of comparative analysis.


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Cell_Biology_Alberts. mutations Reveal the Functions of Genes Without additional information, no amount of gazing at genome sequences will reveal the functions of genes. We may recognize that gene B is like gene A, but how do we discover the function of gene A in the first place? And even if we know the function of gene A, how do we test whether the function of gene B is truly the same as the sequence similarity suggests? How do we connect the world of abstract genetic information with the world of real living organisms?


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Cell_Biology_Alberts. The analysis of gene functions depends on two complementary approaches: genetics and biochemistry. Genetics starts with the study of mutants: we either find or make an organism in which a gene is altered, and then examine the effects on the organism’s structure and performance (Figure 1–23). Biochemistry more directly examines the functions of molecules: here we extract molecules from an organism and then study their chemical activities. By combining genetics and biochemistry, it is possible to find those molecules whose production depends on a given gene. At the same time, careful studies of the performance of the mutant organism show us what role those molecules have in the operation of the organism as a whole. Thus, genetics and biochemistry used in combination with cell biology provide the best way to relate genes and molecules to the structure and function of an organism.


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Cell_Biology_Alberts. In recent years, DNA sequence information and the powerful tools of molecular biology have accelerated progress. From sequence comparisons, we can often identify particular subregions within a gene that have been preserved nearly unchanged over the course of evolution. These conserved subregions are likely to be the most important parts of the gene in terms of function. We can test their individual contributions to the activity of the gene product by creating in the laboratory mutations of specific sites within the gene, or by constructing artificial hybrid genes that combine part of one gene with part of another. Organisms can be engineered to make either the RNA or the protein specified by the gene in large quantities to facilitate biochemical analysis. Specialists in molecular structure can determine the three-dimensional conformation of the gene product, revealing the exact position of every atom in it. Biochemists can determine how each of the


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Cell_Biology_Alberts. Figure 1–23 A mutant phenotype reflecting the function of a gene. A normal yeast (of the species Schizosaccharomyces pombe) is compared with a mutant in which a change in a single gene has converted the cell from a cigar shape (left) to a T shape (right). The mutant gene therefore has a function in the control of cell shape. But how, in molecular terms, does the gene product perform that function? That is a harder question, and it needs biochemical analysis to answer it. (courtesy of kenneth sawin and Paul nurse.) parts of the genetically specified molecule contributes to its chemical behavior. Cell biologists can analyze the behavior of cells that are engineered to express a mutant version of the gene.


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Cell_Biology_Alberts. There is, however, no one simple recipe for discovering a gene’s function, and no simple standard universal format for describing it. We may discover, for example, that the product of a given gene catalyzes a certain chemical reaction, and yet have no idea how or why that reaction is important to the organism. The functional characterization of each new family of gene products, unlike the description of the gene sequences, presents a fresh challenge to the biologist’s ingenuity. Moreover, we will never fully understand the function of a gene until we learn its role in the life of the organism as a whole. To make ultimate sense of gene functions, therefore, we have to study whole organisms, not just molecules or cells. molecular Biology Began with a spotlight on E. coli


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Cell_Biology_Alberts. molecular Biology Began with a spotlight on E. coli Because living organisms are so complex, the more we learn about any particular species, the more attractive it becomes as an object for further study. Each discovery raises new questions and provides new tools with which to tackle general questions in the context of the chosen organism. For this reason, large communities of biologists have become dedicated to studying different aspects of the same model organism.


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Cell_Biology_Alberts. In the early days of molecular biology, the spotlight focused intensely on just one species: the Escherichia coli, or E. coli, bacterium (see Figures 1–13 and 1–14). This small, rod-shaped bacterial cell normally lives in the gut of humans and other vertebrates, but it can be grown easily in a simple nutrient broth in a culture bottle. It adapts to variable chemical conditions and reproduces rapidly, and it can evolve by mutation and selection at a remarkable speed. As with other bacteria, different strains of E. coli, though classified as members of a single species, differ genetically to a much greater degree than do different varieties of a sexually reproducing organism such as a plant or animal. One E. coli strain may possess many hundreds of genes that are absent from another, and the two strains could have as little as 50% of their genes in common. The standard laboratory strain


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Cell_Biology_Alberts. E. coli K-12 has a genome of approximately 4.6 million nucleotide pairs, contained in a single circular molecule of DNA that codes for about 4300 different kinds of proteins (Figure 1–24). In molecular terms, we know more about E. coli than about any other living organism. Most of our understanding of the fundamental mechanisms of life— for example, how cells replicate their DNA, or how they decode the instructions represented in the DNA to direct the synthesis of specific proteins—initially came from studies of E. coli. The basic genetic mechanisms have turned out to be highly conserved throughout evolution: these mechanisms are essentially the same in our own cells as in E. coli.


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Cell_Biology_Alberts. Prokaryotes (cells without a distinct nucleus) are biochemically the most diverse organisms and include species that can obtain all their energy and nutrients from inorganic chemical sources, such as the reactive mixtures of minerals released at hydrothermal vents on the ocean floor—the sort of diet that may have nourished the first living cells 3.5 billion years ago. DNA sequence comparisons reveal the family relationships of living organisms and show that the prokaryotes fall into two groups that diverged early in the course of evolution: the bacteria (or eubacteria) and the archaea. Together with the eukaryotes (cells with a membrane-enclosed nucleus), these constitute the three primary branches of the tree of life.


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Cell_Biology_Alberts. Most bacteria and archaea are small unicellular organisms with compact genomes comprising 1000–6000 genes. Many of the genes within a single organism show strong family resemblances in their DNA sequences, implying that they originated from the same ancestral gene through gene duplication and divergence. Family resemblances (homologies) are also clear when gene sequences are compared between different species, and more than 200 gene families have been so highly (A) 4,639,221 nucleotide pairs Escherichia coli K-12 origin of replication terminus of replication (B) Figure 1–24 The genome of E. coli. (A) A cluster of E. coli cells. (B) A diagram of the genome of


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Cell_Biology_Alberts. E. coli strain k-12. The diagram is circular because the dnA of E. coli, like that of other prokaryotes, forms a single, closed loop. Protein-coding genes are shown as yellow or orange bars, depending on the dnA strand from which they are transcribed; genes encoding only RnA molecules are indicated by green arrows. some genes are transcribed from one strand of the dnA double helix (in a clockwise direction in this diagram), others from the other strand (counterclockwise). (A, courtesy of dr. Tony Brain and david Parker/Photo Researchers; B, adapted from F.R. Blattner et al., Science 277:1453–1462, 1997.) conserved that they can be recognized as common to most species from all three domains of the living world. Thus, given the DNA sequence of a newly discovered gene, it is often possible to deduce the gene’s function from the known function of a homologous gene in an intensively studied model organism, such as the bacterium E. coli.


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Cell_Biology_Alberts. E. coli. Eukaryotic cells, in general, are bigger and more elaborate than prokaryotic cells, and their genomes are bigger and more elaborate, too. The greater size is accompanied by radical differences in cell structure and function. Moreover, many classes of eukaryotic cells form multicellular organisms that attain levels of complexity unmatched by any prokaryote.


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Cell_Biology_Alberts. Because they are so complex, eukaryotes confront molecular biologists with a special set of challenges that will concern us in the rest of this book. Increasingly, biologists attempt to meet these challenges through the analysis and manipulation of the genetic information within cells and organisms. It is therefore important at the outset to know something of the special features of the eukaryotic genome. We begin by briefly discussing how eukaryotic cells are organized, how this reflects their way of life, and how their genomes differ from those of prokaryotes. This leads us to an outline of the strategy by which cell biologists, by exploiting genetic and biochemical information, are attempting to discover how eukaryotic organisms work. eukaryotic cells may have originated as Predators


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Cell_Biology_Alberts. By definition, eukaryotic cells keep their DNA in an internal compartment called the nucleus. The nuclear envelope, a double layer of membrane, surrounds the nucleus and separates the DNA from the cytoplasm. Eukaryotes also have other features that set them apart from prokaryotes (Figure 1–25). Their cells are, typically, 10 times bigger in linear dimension and 1000 times larger in volume. They have an elaborate cytoskeleton—a system of protein filaments crisscrossing the cytoplasm and forming, together with the many proteins that attach to them, a system of girders, ropes, and motors that gives the cell mechanical strength, controls its shape, and drives and guides its movements (Movie 1.1). And the nuclear envelope is only one part of a set of internal membranes, each structurally similar to the plasma membrane and enclosing different types of spaces inside the cell, many of them involved in digestion and secretion. Lacking the tough cell wall of most bacteria, animal cells and the


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Cell_Biology_Alberts. to the plasma membrane and enclosing different types of spaces inside the cell, many of them involved in digestion and secretion. Lacking the tough cell wall of most bacteria, animal cells and the free-living eukaryotic cells called protozoa can change their shape rapidly and engulf other cells and small objects by phagocytosis (Figure 1–26).


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Cell_Biology_Alberts. How all of the unique properties of eukaryotic cells evolved, and in what sequence, is still a mystery. One plausible view, however, is that they are all reflections of the way of life of a primordial cell that was a predator, living by capturing other cells and eating them (Figure 1–27). Such a way of life requires a large cell with a flexible plasma membrane, as well as an elaborate cytoskeleton to support Figure 1–25 The major features of eukaryotic cells. The drawing depicts a typical animal cell, but almost all the same components are found in plants and fungi as well as in single-celled eukaryotes such as yeasts and protozoa. Plant cells contain chloroplasts in addition to the components shown here, and their plasma membrane is surrounded by a tough external wall formed of cellulose.


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Cell_Biology_Alberts. and move this membrane. It may also require that the cell’s long, fragile DNA molecules be sequestered in a separate nuclear compartment, to protect the genome from damage by the movements of the cytoskeleton.


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Cell_Biology_Alberts. A predatory way of life helps to explain another feature of eukaryotic cells. All such cells contain (or at one time did contain) mitochondria (Figure 1–28). These small bodies in the cytoplasm, enclosed by a double layer of membrane, take up oxygen and harness energy from the oxidation of food molecules—such as sugars—to produce most of the ATP that powers the cell’s activities. Mitochondria are similar in size to small bacteria, and, like bacteria, they have their own genome in the form of a circular DNA molecule, their own ribosomes that differ from those elsewhere in the eukaryotic cell, and their own transfer RNAs. It is now generally accepted that mitochondria originated from free-living oxygen-metabolizing (aerobic) bacteria that were engulfed by an ancestral cell that could otherwise make no such use of oxygen (that is, was anaerobic). Escaping digestion, these bacteria evolved in symbiosis with the engulfing cell and its progeny, receiving


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Cell_Biology_Alberts. Figure 1–27 A single-celled eukaryote that eats other cells. (A) Didinium is a carnivorous protozoan, belonging to the group known as ciliates. It has a globular body, about 150 μm in diameter, encircled by two fringes of cilia—sinuous, whiplike appendages that beat continually; its front end is flattened except for a single protrusion, rather like a snout. (B) A Didinium engulfing its prey. Didinium normally swims around in the water at high speed by means of the synchronous beating of its cilia. When it encounters a suitable prey (yellow), usually another type of protozoan, it releases numerous small paralyzing darts from its snout region. Then, the Didinium attaches to and devours the other cell by phagocytosis, inverting like a hollow ball to engulf its victim, which can be almost as large as itself. (courtesy of d. Barlow.)


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Cell_Biology_Alberts. Figure 1–26 Phagocytosis. This series of stills from a movie shows a human white blood cell (a neutrophil) engulfing a red blood cell (artificially colored red) that has been treated with an antibody that marks it for destruction (see movie 13.5). (courtesy of stephen e. malawista and Anne de Boisfleury chevance.) shelter and nourishment in return for the power generation they performed for their hosts. This partnership between a primitive anaerobic predator cell and an aerobic bacterial cell is thought to have been established about 1.5 billion years ago, when the Earth’s atmosphere first became rich in oxygen. As indicated in Figure 1–29, recent genomic analyses suggest that the first eukaryotic cells formed after an archaeal cell engulfed an aerobic bacterium. This would explain why all eukaryotic cells today, including those that live as strict anaerobes show clear evidence that they once contained mitochondria.


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Cell_Biology_Alberts. Many eukaryotic cells—specifically, those of plants and algae—also contain another class of small membrane-enclosed organelles somewhat similar to mitochondria—the chloroplasts (Figure 1–30). Chloroplasts perform photosynthesis, using the energy of sunlight to synthesize carbohydrates from atmospheric carbon dioxide and water, and deliver the products to the host cell as food. Like mitochondria, chloroplasts have their own genome. They almost certainly originated as symbiotic photosynthetic bacteria, acquired by eukaryotic cells that already possessed mitochondria (Figure 1–31).


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Cell_Biology_Alberts. A eukaryotic cell equipped with chloroplasts has no need to chase after other cells as prey; it is nourished by the captive chloroplasts it has inherited from its ancestors. Correspondingly, plant cells, although they possess the cytoskeletal equipment for movement, have lost the ability to change shape rapidly and to engulf other cells by phagocytosis. Instead, they create around themselves a tough, protective cell wall. If the first eukaryotic cells were predators on other organisms, we can view plant cells as cells that have made the transition from hunting to farming. Fungi represent yet another eukaryotic way of life. Fungal cells, like animal cells, possess mitochondria but not chloroplasts; but in contrast with animal cells and protozoa, they have a tough outer wall that limits their ability to move rapidly Figure 1–28 A mitochondrion. (A) A cross section, as seen in the electron microscope.


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Cell_Biology_Alberts. Figure 1–28 A mitochondrion. (A) A cross section, as seen in the electron microscope. (B) A drawing of a mitochondrion with part of it cut away to show the three-dimensional structure (Movie 1.2). (c) A schematic eukaryotic cell, with the interior space of a mitochondrion, containing the mitochondrial dnA and ribosomes, colored. note the smooth outer membrane and the convoluted inner membrane, which houses the proteins that generate ATP from the oxidation of food molecules. (A, courtesy of daniel s. Friend.) Figure 1–29 The origin of mitochondria. archaeon) is thought to have engulfed the bacterial ancestor of mitochondria, initiating a symbiotic relationship. clear evidence of a dual bacterial and archaeal inheritance can be discerned today in the genomes of all eukaryotes.


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Cell_Biology_Alberts. or to swallow up other cells. Fungi, it seems, have turned from hunters into scavengers: other cells secrete nutrient molecules or release them upon death, and fungi feed on these leavings—performing whatever digestion is necessary extracellularly, by secreting digestive enzymes to the exterior.


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Cell_Biology_Alberts. The genetic information of eukaryotic cells has a hybrid origin—from the ancestral anaerobic archaeal cell, and from the bacteria that it adopted as symbionts. Most of this information is stored in the nucleus, but a small amount remains inside the mitochondria and, for plant and algal cells, in the chloroplasts. When mitochondrial DNA and the chloroplast DNA are separated from the nuclear DNA and individually analyzed and sequenced, the mitochondrial and chloroplast genomes are found to be degenerate, cut-down versions of the corresponding bacterial genomes. In a human cell, for example, the mitochondrial genome consists of only 16,569 nucleotide pairs, and codes for only 13 proteins, 2 ribosomal RNA components, and 22 transfer RNAs.