The conserved genome

Something has to make a start, and a paper we recently discussed at SMU shall be it.

Along the lines of “it’s not about what (genes) you have but how you use them”, I came across this recent article: Systematic discovery of nonobvious human disease models through orthologous phenotypes .

The article itself seems, well, nonobvious at first. The subject is in the area of cross species genome comparisons. In essence, the more becomes known about genomes, the more people find similar genes in very dissimilar organisms. More, many genes appear in functional clusters, and these clusters are also to a large extent preserved in their unity across species and even phyla. Their genes do produce proteins with similar biochemical functions, but those same chemical functions in similar functional clusters produce very different outcomes (phenotypes) depending on the organism in which they occur – they perform totally unrelated organismal functions. So, structure is preserved, function is not, and the more is known about genes the more it appears that true novelty is rare and that most innovation in terms of species, depends on recycling and differently regulating existing genes.

There are many ways of looking at this – the surprising flexibility of genes and gene products themselves for instance to be reused for different functions, so that say, cilia related genes of unicellular organism have functions in producing neuronal networks in higher organisms. There is the aspect of finding new disease models by going from known disease related genes in humans, to finding new genes in the homologous genetic module of some different organism just by virtue of finding them together with unknown genes there.

To me this is yet another piece of evidence for one of my pet theories, that genes seems to be widely conserved, and that patterns of use and gene regulation are much more important for expressed features of organisms, than the nominally encoded genetic information. More and more, genes seem to be a rather generic thing, and that the differences in organisms seems to come about in how these genes are being used. On a higher level, this ties in with other puzzling facts of life, such as, why are plant drugs effective in humans at all? Why are very different looking and acting species so widely genetically similar?

The mix and match way of construction and innovation that life uses over and over – to simply re-use “old” genes that have been “invented” for an entirely different purpose – also offers a nice parallel to the way technology produces innovation by recombination of existing parts. One could have called this article “Life as ‘bricolage’: Innovation by recycling parts.”.

Here is some lighter reading on this paper, with background information.

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Posted on 2010/05/11, in Debate paper SMU, Science news and tagged , . Bookmark the permalink. 7 Comments.

  1. Yes. I find this both obvious (now, not ten years ago) and obviously disturbing. When we thought that there was a one-to-one correspondence between genes and proteins, and a many-to-one relationship between proteins and attributes, evolution made sense. “These three genes produce these three proteins, which together determine if your hair looks Nordic or African” … that sort of thing. Many-to-many relationships, with an identical or nearly identical protein producing one physical expression in mustard and an entirely different physical expression in mollusks (just to be arbitrary and, I hope, hypothetical) is much too complicated to figure out. If everything is a function of everything else, complex life is indeed a wildly implausible accident.

  2. And wow … I did not know that as informal as this website it, comments needed a moderator.

  3. Welcome Eric! – The moderation function is to protect against all sorts of things, from spamming robots to possibly unkind contributions. RIght now this should happen only at the beginning (first post) or when there are several links in a post (could indicate robot spam).

  4. Eric, maybe the point is that processes such as alternative splicing really evolved in order to be able to use these conserved gene clusters that organisms became somehow “stuck with”, and which made no sense in their original form and utility. And there must be other biochemistry in the cell as well that leads to a different phenotypic outcome across ages and phyla.

    I really like the ‘bricolage’ metaphor btw for this, with nods to Levi-Strauss – he thought of ‘bricolage’ in a cultural way, that cultures pick up and re-use bits and pieces of tradition and culture by giving them a different meaning, doing a kind or DIY = bricolage. Somehow it must be easier to take any old genome bits and pieces and recycle them in a different emulation, than to build new ones from scratch.

  5. I find this remarkably unsurprising. If most genetic variation is created by genetic recombination (a much less risky mechanism than single gene mutation) then one would expect that (1) most genes, and groups of genes, will be conserved and (2) that variation will be in terms of “everything is a function of everything else”. In fact, this seems a far more plausible mechanism for life spread than a genetically diverging path.

    The t-RNA work in part demonstrated that DNA functional groups often have end markers/protectors which help keep these chunks intact. Assuming this protection is maintained during genetic cross-over (and I’d expect it would) then there’s also no surprise that they persist – even over widely disparate organisms – since much of the gene groups would be very very old.

  6. Kevin, the surprise to me, if any, came in that the conserved groups would be conserved in structure but not in phenotypic function (though biochemical function seems to be rather conserved). In all else this plays in favor of my current thinking re: evolution – unicellular life creating the majority of currently existing biochemical pathways due to their high mutation rate, short generation time, and therefore massive variation and selection processes. And then, re-use of this conserved “canon” of genes in the emerging multicellular life – without quantitatively substantial alteration to the principal biochemistry.

    As you are saying, the sexual recombination in multicellular life allows for massive combinatorial variation without substantial risk of fatal errors at the gene level. The combinatorial pathway for variation is actually the only viable one for complex genomes since they’d otherwise run into gene pool degeneration due to complexity catastrophe (accumulation of errors in all genomes, therefore no weeding out through selection). So I am happy this paper goes to corroborate my hunch… but I am still puzzled how subsequent organisms could re-rout gene clusters to such different functions, especially since they seem internally linked as per this paper.

  7. I agree, the degree of phenotypic function variation over conserved biochemical function is stunning. Life is very impressive.

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