title: Evidence for positive selection on a number of MicroRNA regulatory interactions during recent human evolution.
abstract: MicroRNA (miRNA)-mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution.
authors.affiliation: Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Toronto, Canada.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xin
authors.forename: Taehyung Simon
authors.initials: TS
authors.lastname: Kim
authors.forename: Eduardo Aguiar
authors.initials: EA
authors.lastname: Cabeza
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000220:Adaptation, Biological / Q000528:radiation effects; D000483:Alleles; D001665:Binding Sites; D005075:Biological Evolution; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011110:Polymorphism, Genetic; D012641:Selection, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C524942:MIRN155 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D010088:Oxidoreductases; C489799:TYRP1 protein, human