22 May 2012

Never send a sibling to do a clone’s job: Part 1

Today, a guest post from Kyle McLea, who has been carrying the Marmorkrebs banner for this round of #SciFund.

As a crustacean biologist who has chiefly studied crabs and lobsters, I’ve been fascinated by the marbled crayfish (Marmorkrebs) for years and for a number of reasons that I’ll detail below. But the first thing that attracted me was simply this.

Really? A crayfish that clones itself?

When Doctor Zen asked me to guest blog on the Marmorkrebs blog I was sure I had a lot to say about my interest in these fascinating critters, but I also wanted to speak to the wider interest of the scientific community. In short: Why should scientists (and the public) care?

To which I say: Never send a (mere) sibling to do a clone’s job.

Let me explain.

Marmorkrebs are a parthenogenetic crayfish. All known examples are female and reproduce themselves entirely without sex. This makes it the first example of a decapod crustacean (and there ~15,000 known species of crabs, lobsters, shrimp, and crayfish!) that only reproduces asexually. There have been a couple of other examples of crayfish that have been found to be genetically identical or to sometimes reproduce asexually, but marbled crayfish were the first found to procreate this way exclusively.

So, in a word, we’re dealing with clone crayfish.

To anyone who’s been following the molecular biology revolution over the past 30ish years, the word clone has both amazing power and amazing misuse and confusion. Clone can mean a lot of things. In this case, I’m not talking about cloning genes (experimentally extracting pieces of nucleic acid, sequencing them, and using them to assemble recombinant—new—combinations of DNA sequence for introduction to a different organism) or about using somatic-cell nuclear transfer to clone embryos (like Dolly the sheep). What I’m saying is that mother and daughter marbled crayfish should be genetically identical, or nearly so, much like identical twins in humans.

It turns out that scientists have thought a lot about the benefits of studying genetically identical individuals in a population, pretty much for as long as there has been a science of genetics. Case in point for inbred (nearly genetically identical) organisms:

“Just as the purity of the chemical assures the pharmacist of the proper filling of the doctor’s prescription, so the purity of the mouse stock can assure a research scientist of a true and sure experiment...In experimental medicine today... the use of in-bred genetic material... is just as necessary as the use of aseptic and anti-septic precautions in surgery.” —C.C. Little, 1936

Now Little may have held some ill-conceived notions about eugenics and the role of tobacco in causing cancer, but on the importance of genetically-identical (isogenic) and inbred laboratory strains he was a pioneer. His work to build up the Jackson Laboratory in Bar Harbor, Maine (the mecca of 5000 unique strains of mice), was a key part of the rise of defined strains and breeds of laboratory animals that continues today.

Those laboratory strains serve as “models” for various human diseases and for particular functions of human physiology, such as immunity or heart function. Among the model organisms listed at NIH, for instance, everything from yeast to mouse and Daphnia to zebrafish can help us to learn about different aspects of human biology and beyond.

But in each case the normal biological variation within an organism confounds us and complicates our study. Unless we want to see the full extent of biological variance (and sometimes we do—safety and efficacy testing of drugs on different populations, anyone?), having organisms that are as close to identical as possible is (often) the goal.

For mice and rats, you might have to backcross (do parent/offspring matings) for more than 20 generations to have a sufficiently inbred line to call it “genetically identical” (and I suspect some gene variation may still exist). Now, mice breed fast, but 20 generations is still real time (years) in the life of a scientist. In the mean time, scientists resort to use of siblings, littermates, or much less inbred animals. These animals have many more differences at the genetic level.

I know you’re seeing where I’m going with this… if an organism started out genetically identical, you’d have a great edge in using this organism to study any number of interesting things. Bringing us back to Marmorkrebs.

Lines of the marbled crayfish are believed to be genetically identical because they do not participate in the normal exchange and shuffling process that accompanies sexual reproduction. But of course, mutations happen to us all. So they’re not likely to be absolutely 100% identical between individuals, but much closer than anything else in the world except for natural identical twins/triplets/etc.

So, I say, send in the clone crayfish. With these animals, we don’t need to compare results with a genetically-different sibling or with an unrelated animal. This unique animal can not only be a useful biological model, but we also don’t have any easily-reared decapod crustacean that can really compete with marbled crayfish, if you take into account their genetic identity.

While they might not be a great model organism for general human physiology (they are crustaceans, after all), there are some specific ways they can help us understand human physiology (e.g., nerves) and they have a lot of other potential uses as a model organism.

Kyle, scientist at Colorado State University and science blogger at By Way of Science. Come back next week for Part 2!

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