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May 11, 2011 / Dr. Toad

The Interpretation of Frogs

A person’s, or a frog’s, genes can be of two types: they can code for proteins that build the cells, or they can code for a mechanism that regulates the production of that protein from genes of the first type.

It Takes 30, by Rebecca Ward, the systems biology department head at the Harvard Medical School, writes:

One of the surprising findings of the molecular age, which has become even clearer as genome sequence becomes more available, is that changes in protein coding sequences are less prevalent than changes in sequences that may affect the regulation of a gene.  This is rather irritating because […] it’s not easy to use sequence information to predict how the expression of a gene might change.  So there’s not a great deal of information on whether and when different species use the same gene (or set of genes) at different times, or whether and when a gene is expressed to a higher level in one species relative to another.

Dr. Toad is partial to any news about amphibians, especially of the order Anura, especially when a personal friend makes an interesting discovery. So, there are these two species of frogs, they’re related, but their species have diverged sometime between 30 and 90 million years ago, and they have very similar developmental stages, but they clearly also have morphological differences:

Two Xenopus species: X. tropicalis and X. laevis

Xenopus laevis (left) and X. tropicalis

What Itai Yanai, Leon Peshkin and scientists at the Harvard Medical School did was to trace out precisely the expression of thousands of genes in the two species over the course of the organisms’ development: from fertilized egg to adult frog.

They found some interesting things, like a few timing differences in the expression of genes between X. laevis and X. tropicalis. For example, the latter activates the development of its immune system sooner than the former, perhaps because it lives in a higher-temperature environments where bacteria may be more prevalent. But much more common were differences in the amount of expression of a particular gene or a bloc of genes: how often, how much protein of the kind that gene codes for is actually made.

Peshkin likes to imagine the differences in gene expression between related species like musical interpretation of the same score by musicians playing different instruments:

Two frogs playing out their DNA

Artwork by Piotr Parda, http://www.par-don.com/piotr.

If so, these frogs are not too much like the Jazz musicians who “play the same tune, just not at the same time” (who said that?). It’s more like the sheet music in front of them represents only pitch, and they get to make up their own note values and dynamics, their own quarters and halves, their own pianos and fortes.

Perhaps this metaphor breaks down here, because actually all those note values and dynamics are part of the score / genome, they are the parts that code for regulatory mechanisms… Well, it was a fun image while it lasted.

Meanwhile, the huge amount of data and the computational tools that this endeavor has generated will be a great help for figuring out which genes code for regulating which other genes’ expression and how. And that, in turn, should help us understand more about the evolution of species, and not only species of frogs.

Links: It Takes 30, the paper in the April issue of Cell, an online tool to check the timeline of gene expression in the two frogs.

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