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Nucleic Acids Res. 2015 Jul 27;43(13):6399-412. doi: 10.1093/nar/gkv580. Epub 2015 Jun 11.

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

Author information

1
Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
2
Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA Department of Computer Science and Engineering, University of Connecticut, Storrs, CT 06269-2155, USA.
3
Department of Computer Science and Engineering, University of Connecticut, Storrs, CT 06269-2155, USA.
4
Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA martin.schiller@unlv.edu.

Abstract

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 ∼300 000 minimotifs in 1092 human genomes from the 1000 Genomes Project. Most minimotifs 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.

PMID:
26068475
PMCID:
PMC4513861
DOI:
10.1093/nar/gkv580
[Indexed for MEDLINE]
Free PMC Article

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