Gene Evolution Is All about Regulation

Okay, so gene evolution isn’t entirely about regulation. But protein-coding sequences of genes have changed comparatively little over hundreds of millions of years. When you look at the proteins that a human produces and compare them to the zebrafish, there are homologues (i.e., near matches) about 70% of the time [1]. The zebrafish has many duplicates of genes because of a massive duplication of its genome after our two lines split about 450 million years ago. But when you think that there’s roughly only about a 30% difference in the types of genes that our two species have, the level of conservation is astounding for the evolutionary span that separates us.

zebrafish.jpg

Danio rerio, the zebrafish.

Scientists believe therefore that the bulk of the differences between species, such as ourselves and zebrafish, lies largely within evolution of the DNA sequences that regulate gene expression. These variations in regulation can lead to changes in a variety of ways.

For one, there may be differences in the transcripts produced from a single gene, as well as how much of a given transcript is produced. Most genes produce multiple variations of the same gene, each one having modestly different functions. Variations in gene regulation can also lead to different expression patterns of a transcript across organs of the body or even adjacent tissues within the same organ, such as regions of the brain. And finally, gene regulation can alter patterns of the cell stages during which a gene transcript is expressed. This can lead, for instance, to variations in the structure of a tissue or organ. As an example, the differences between males and females are believed to be largely due to differences in the timing of specific gene expression between the sexes, as opposed to differences necessarily in kind [2].

adam-and-eve-lucas-cranach-the-elder-1526

Differences between species, therefore, are largely a matter of:

  • What
  • When
  • Where
  • How much

of a gene transcript is produced. There are many elements that work to control these expression patterns, and their numbers appear to increase as species complexity has increased. So, for instance, in the yeast genome, each gene has about 20 transcription factors that regulate it– while in humans there are twice as many. This increasing complexity has undoubtedly had exponential effects [3].

Many of the regulatory sequences in and surrounding genes are also well-conserved across species. These sequences can be sites for transcription factor binding as mentioned above, tethering sequences that help a factor locate its DNA target, insulators that keep adjacent elements from targeting the wrong regulatory sequence, and repressors that negatively regulate gene expression [3]. Many conserved regions of the DNA are also RNA genes, that don’t ultimately code for a protein but perform no-less-vital functions in cell metabolism. In fact, many non-coding RNA genes are thought to regulate protein-coding genes.

So you see, in spite of our focus for the last half century on the protein-coding sequences in the genome, it’s clear that these are in fact very well conserved across hundreds of millions of years. Which makes sense because they are so fundamental and the loss or duplication of a single protein-coding sequence can and usually does have disastrous effects on development. Instead, evolution has played around with subtler ways to regulate these same genes, and in doing so, has led to exceptional species variety. Thus, it’s not the number of building blocks you start out with, but what you do with them that counts.

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6 responses to “Gene Evolution Is All about Regulation

  1. This!

    I know it’s really a quite ancillary point –but my sole lab-coat is at the cleaners and I’m stuck in a social-studies mode for the moment–if I read you correctly, there really is no good foundation in voting for Hillary Clinton solely because she’s a woman, correct? That is, from a genetic point of view, a man might do just as well?

    • Ah, alas, not so! 😉 Because differences between men and women may largely be one of developmental timing (cultural influences aside for the moment), that leads to structural and thus functional differences between the two sexes– just as there are more extreme structural and functional differences amongst species. You may enjoy reading about heterochrony amongst species. http://link.springer.com/article/10.1007/s12052-012-0420-3#page-1 A good review article. Let me know if you’d like me to send you a copy (albeit one that’s been highlighted).

  2. Re : …”there’s roughly only about a 30% difference in the types of genes that our two species have, “…

    To help your lay-readers understand the importance of this, can you say a brief word about what “a 30% difference” means?

    Thanks!

    • The 30% difference primarily refers to the genes that the zebrafish and human don’t share in common and there are no homologues for. This is a drastic simplification, since obviously there can be changes to the sequences of the protein-coding genes they do have in common that could perhaps result in completely different functions in the two species. But the 30% is simply an extension of the finding that humans and zebrafish share about 70% of their protein-coding genes in common. Does that help any? 🙂

      • RE : “Let me know if you’d like me to send you a copy (albeit one that’s been highlighted).”

        Yes, please! , ^)

        —————————
        RE : “But the 30% is simply an extension of the finding that humans and zebra-fish share about 70% of their protein-coding genes in common. Does that help any?”

        Honestly? Not a _great_ deal. I had actually figured out that much. 70% homologous genes.

        But I project my own modest understanding to others and wonder if they have, as I have, wondered about the difference between frequency of homologous genetic material and the significance of the differences between one thang and another thang–be they plant or critter. I thought about this while waiting for the bus yesterday.

        We say there’s a 70% similarity in the gene material in this case. (In other cases, see, e.g. this article at National Geographic (I write to my fellow non-experts ;^) ): http://ngm.nationalgeographic.com/2013/07/125-explore/shared-genes ) I gather that means that, if we were drawing out bits of this material at random, 70% of the time, we’d draw a homologous bit while 30% of the time, the material would not be common to the two critters. But I suspect that that by itself doesn’t really mean that we’re all 88% “like a mouse,” 65% “like a chicken,” and 47% “like a fruit-fly”, or does it?

        I think these percentages may mislead some people to overestimate the importance of the amount of “shared” material. If we share, for example, even _more_ than (?) 90% homologous gene material with chimpanzees–and, having recently spent MUCH time observing British political practice, I mean no disrespect to chimpanzees at all! — it seems to me that this less-than-10-percent difference is, in effect, HUGE. Is it true that in fact a tiny difference in percent can account for truly immense differences in character and capacities? I tend to get this impression. Thus, I wonder if the percentages don’t create more confusion than clarity.

      • Well but you’ve hit on the major point of the article, that while the protein-coding sequences may be very similar or even identical across certain species, the non-coding sequences are typically NOT the same and are likely the major drivers of differential expression of those same genes across species. So, for instance, human and chimp may have virtually the same amino acid sequence derived from the CNTNAP2 gene, they have different species-specific enhancers for that gene that leads to considerably different expression patterns. http://www.sciencedirect.com/science/article/pii/S0092867415010880 So, yes, the 30%/70% is a DRASTIC oversimplification. But that’s the whole point of the blog. 🙂

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