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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.