title: Natural variability of minimotifs in 1092 people indicates that minimotifs are targets of evolution.
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.
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Lyon
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Strong
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Steve G
authors.initials: SG
authors.lastname: Schooler
authors.affiliation: 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.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Young
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Nervik
authors.initials: N
authors.lastname: Roy
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Ozar
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4004, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bachmeier
authors.affiliation: Department of Computer Science and Engineering, University of Connecticut, Storrs, CT 06269-2155, USA.
authors.forename: Sanguthevar
authors.initials: S
authors.lastname: Rajasekaran
authors.affiliation: 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.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Schiller
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D019143:Evolution, Molecular; D015894:Genome, Human; D006657:Histones / Q000737:chemistry; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D006657:Histones