September 30, 2008

Disease genes are ancient genes

A very interesting paper, which shows that genes that cause human disease tend to be those which appeared earlier in evolution on Earth, rather than in the mammalian lineage. Perhaps, ancient genes are very important for the proper functioning of an organism (they managed to survive the longest, so they must be doing something important), and hence dysfunctions caused by them would have a major negative effect.

Molecular Biology and Evolution, doi:10.1093/molbev/msn214

An ancient evolutionary origin of genes associated with human genetic diseases

Tomislav Domazet-Loo and Diethard Tautz

Abstract

Several thousand genes in the human genome have been linked to a heritable genetic disease. The majority of these appear to be non-essential genes (i.e. are not embryonically lethal when inactivated) and one could therefore speculate that they are late additions in the evolutionary lineage towards humans. Contrary to this expectation, we find that they are in fact significantly over-represented among the genes that have emerged during the early evolution of the metazoa. Using a phylostratigraphic approach, we have studied the evolutionary emergence of such genes at 19 phylogenetic levels. The majority of disease genes was already present in the eukaryotic ancestor and the second largest number has arisen around the time of evolution of multicellularity. Conversely, genes specific to the mammalian lineage are highly underrepresented. Hence, genes involved in genetic diseases are not simply a random subset of all genes in the genome, but are biased towards ancient genes.

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