%0 Journal Article
%T Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations
%A Guojie Zhang
%A Zhang Pei
%A Edward V Ball
%A Matthew Mort
%A Hildegard Kehrer-Sawatzki
%A David N Cooper
%J Human Genomics
%D 2011
%I BioMed Central
%R 10.1186/1479-7364-5-5-453
%X The recent publication of the draft sequence of the Neanderthal genome [1] ushered in a new age in molecular archaeology [2,3]. This achievement was followed closely by the publication of the draft genome sequence (1.9-fold coverage) of a ~50,000-year old archaic hominin from Denisova Cave in southern Siberia [4]. This hominin (a 'Denisovan') is thought to have been a member of a sister group of hominins to the Neanderthals with whom they lived sympatrically during the Upper Pleistocene [4-7]. Denisovans appear to be more closely related to Neanderthals than humans, having diverged from Neanderthals about 640,000 years ago and from extant Africans about 804,000 years ago [4].Access to DNA sequence data from ancient hominins not only promises to revolutionise our knowledge of hominin relationships, but is also potentially informative in the context of exploring the molecular basis of human genetic disease [8,9]. We have previously cross-compared the human, chimpanzee and Neanderthal genome sequences with a set of disease-causing/disease-associated missense and regulatory mutations in order to identify genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species ('potentially compensated mutations' [PCMs]) [10]. PCMs correspond to variants that may have been deleterious for a certain period of evolutionary time but which persisted long enough in a given population or species to have become positively selected upon the introduction of a 'compensatory' nucleotide change [8,11-14]. Such compensatory changes are thought to be localised in the same gene as the PCM [15]. Not only do PCMs represent excellent candidates for recent population-specific selection (with different alleles having exhibited differential functional importance in different environments), but they may also furnish us with new insights into the genetic basis of susceptibility to common diseases [8,14]. Here, in a
%K Human
%K chimpanzee
%K Neanderthal
%K Denisovan hominin
%K genome sequence
%K potentially compensated mutations
%K disease
%U http://www.humgenomics.com/content/5/5/453