An ancient evolutionary origin of genes associated with human genetic diseases

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An ancient evolutionary origin of genes associated with human genetic

diseases

Abstract here - Free full pdf text at

http://mbe.oxfordjournals.org/cgi/content/abstract/msn214v1

Tomislav Domazet-Loo1,2 and Diethard Tautz1,3

1 Max-Planck Institut für Evolutionsbiologie, August-

Thienemannstrasse 2, 24306 Plön, Germany, Phone: 04522 763 390; Fax:

04522 763 281

2 Laboratory of Evolutionary Genetics, Division of Molecular Biology,

Ruer Bokovi Institute, Bijenika cesta 54, P.P. 180, 10002 Zagreb,

Croatia

3 Max-Planck Institut für Evolutionsbiologie, August-

Thienemannstrasse 2, 24306 Plön, Germany Phone: 04522 763 390; Fax:

04522 763 281

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.