journal.pbio.0030042.pdf (185.97 kB)
Evidence of widespread degradation of gene control regions in hominid genomes
journal contribution
posted on 2023-06-07, 20:10 authored by Peter D Keightley, Martin J Lercher, Adam Eyre-WalkerAdam Eyre-WalkerAlthough 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.
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- Published
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- Published version
Journal
PLoS BiologyISSN
1544-9173Publisher
Public Library of ScienceExternal DOI
Issue
2Volume
3Page range
282-288Pages
7.0Department affiliated with
- Evolution, Behaviour and Environment Publications
Notes
The first evidence that gene control regions have undergone extensive degradation in hominids. AEW designed one of the two central analyses in the paper, did part of the analysis and co-wrote the paper.Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-11-18Usage metrics
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