Natural variability of minimotifs in 1092 people indicates that minimotifs are targets of evolution

作者：Lyon Kenneth F; Strong Christy L; Schooler Steve G; Young Richard J; Roy Nervik; Ozar Brittany; Bachmeier Mark II; Rajasekaran Sanguthevar; Schiller Martin R^*

来源：Nucleic Acids Research, 2015, 43(13): 6399-6412.

DOI：10.1093/nar/gkv580

Since the function of a short contiguous peptide minimotif can be introduced or eliminated by a single point mutation, these functional elements may be a source of human variation and a target of selection. We analyzed the variability of similar to 300 000 minimotifs in 1092 human genomes from the 1000 Genomes Project. Mostminimotifs have been purified by selection, with a 94% invariance, which supports important functional roles for minimotifs. Minimotifs are generally under negative selection, possessing high genomic evolutionary rate profiling (GERP) and sitewise likelihood-ratio (SLR) scores. Some are subject to neutral drift or positive selection, similar to coding regions. Most SNPs in minimotif were common variants, but with minor allele frequencies generally < 10%. This was supported by low substation rates and few newly derived minimotifs. Several minimotif alleles showed different intercontinental and regional geographic distributions, strongly suggesting a role for minimotifs in adaptive evolution. We also note that 4% of PTM minimotif sites in histone tails were common variants, which has the potential to differentially affect DNA packaging among individuals. In conclusion, minimotifs are a source of functional genetic variation in the human population; thus, they are likely to be an important target of selection and evolution.

• 出版日期2015-7-27