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PLoS Biol. 2005 Feb;3(2):e42. Epub 2005 Jan 25.

Evidence for widespread degradation of gene control regions in hominid genomes.

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  • 1School of Biological Sciences, University of Edinburgh, United Kingdom. Hominid.Degradation@spambob.net <Hominid.Degradation@spambob.net>

Abstract

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human-chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees.

PMID:
15678168
[PubMed - indexed for MEDLINE]
PMCID:
PMC544929
Free PMC Article

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