Saturday, August 14, 2010

Some paper concludes that complex organism has more functional bases

The conclusion of a recent paper last week, in particular this last sentence from the paper’s abstract, says: "This suggests that, rather than genome size or protein-coding gene complement, it is the number of functional bases that might best mirror our naïve preconceptions of organismal complexity." (1)

The paper is still in part based on the neutral theory that is not true in my opinion for macroevolution. Thus, it concludes that human has about 90% neutral bases while only 10% constrained functional bases. But my study based on the First Axiom of Biology suggests that human has only about 0.1% neutral bases, equivalent to the number of SNPs we find in humans (manuscript in preparation).

So, if the paper’s methodology and interpretation are in part based on the neutral theory, it would not be appropriate to consider its conclusions valid or meaningful. But it is still interesting to see that someone could somehow come to a conclusion that is at least partly in line with the First Axiom of Biology, which says that genetic diversity is inversely related to epigenetic complexity (2). The more complex the organism, the less random variation in the building blocks such as DNA. Or, the more complex the organism, the more the functional bases, and the less the neutral bases.

Reference:
1. Meader, S., Ponting, C.P., and Lunter, G. Massive Turnover of Functional Sequence in Human and Other Mammalian Genomes, (2010) Genome Research. Published on line August 6, 2010. http://genome.cshlp.org/content/early/2010/08/05/gr.108795.110.full.pdf

2. 1. Huang, S.(2009) Inverse relationship between genetic diversity and epigenetic complexity. Preprint available, Nature Precedings;


Here is the abstract of the paper:
Despite the availability of dozens of animal genome sequences, two key questions remain unanswered: first, what fraction of any species‟ genome confers biological function, and second, are apparent differences in organismal complexity reflected in an objective measure of genomic complexity? Here, we address both questions by applying, across the mammalian phylogeny, an evolutionary model that estimates the amount of functional DNA that is shared between two species‟ genomes. Our main findings are, first, that as the divergence between mammalian species increases, the predicted amount of pairwise shared functional sequence drops off dramatically. We show by simulations that this is not an artefact of the method, but rather indicates that functional (and mostly non-coding) sequence is turning over at a very high rate. We estimate that between 200 and 300 Mb (~6.5 – 10%) of the human genome is under functional constraint which includes 5-8 times as many constrained non-coding bases than bases that code for protein. By contrast, in D. melanogaster we estimate only 56-66 Mb to be constrained, implying a ratio of non-coding to coding constrained bases of about 2. This suggests that, rather than genome size or protein-coding gene complement, it is the number of functional bases that might best mirror our naïve preconceptions of organismal complexity.