title: Genome-Wide microRNA Binding Site Variation between Extinct Wild Aurochs and Modern Cattle Identifies Candidate microRNA-Regulated Domestication Genes.
abstract: The domestication of cattle from the now-extinct wild aurochs (Bos primigenius) involved selection for physiological and behavioral traits, with underlying genetic factors that remain largely unknown. Non-coding microRNAs have emerged as key regulators of the spatio-temporal expression of target genes controlling mammalian growth and development, including in livestock species. During the domestication process, selection of mutational changes in miRNAs and/or miRNA binding sites could have provided a mechanism to generate some of the traits that differentiate domesticated cattle from wild aurochs. To investigate this, we analyzed the open reading frame DNA sequence of 19,994 orthologous protein-coding gene pairs from extantBos taurusgenomes and a single extinctB. primigeniusgenome. We identified miRNA binding site polymorphisms in the 3' UTRs of 1,620 of these orthologous genes. These 1,620 genes with altered miRNA binding sites between theB. taurusandB. primigeniuslineages represent candidate domestication genes. Using a novel Score Site ratio metric we have ranked these miRNA-regulated genes according to the extent of divergence between miRNA binding site presence, frequency and copy number between the orthologous genes fromB. taurusandB. primigenius.This provides an unbiased approach to identify cattle genes that have undergone the most changes in miRNA binding (i.e., regulation) between the wild aurochs and modern-day cattle breeds. In addition, we demonstrate that these 1,620 candidate domestication genes are enriched for roles in pigmentation, fertility, neurobiology, metabolism, immunity and production traits (including milk quality and feed efficiency). Our findings suggest that directional selection of miRNA regulatory variants was important in the domestication and subsequent artificial selection that gave rise to modern taurine cattle.
authors.affiliation: Genetics and Biotechnology Lab, Plant and AgriBiosciences Research Centre, School of Natural Sciences, National University of Ireland Galway, University Road Galway, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Braud
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin Dublin, Ireland.
authors.forename: David A
authors.initials: DA
authors.lastname: Magee
authors.affiliation: IdentiGEN Ltd, Unit 2, Trinity Enterprise Centre Dublin, Ireland.
authors.forename: Stephen D E
authors.initials: SD
authors.lastname: Park
authors.affiliation: Recombinetics, Inc., St. Paul MN, USA.
authors.forename: Tad S
authors.initials: TS
authors.lastname: Sonstegard
authors.affiliation: Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc Dunsany, Ireland.
authors.forename: Sinead M
authors.initials: SM
authors.lastname: Waters
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College DublinDublin, Ireland; UCD Conway Institute of Biomolecular and Biomedical Research, University College DublinDublin, Ireland.
authors.forename: David E
authors.initials: DE
authors.lastname: MacHugh
authors.affiliation: Genetics and Biotechnology Lab, Plant and AgriBiosciences Research Centre, School of Natural Sciences, National University of Ireland Galway, University Road Galway, Ireland.
authors.forename: Charles
authors.initials: C
authors.lastname: Spillane
keywords: Bos primigenius; Bos taurus; agriculture; ancient DNA; domestication; evolution; microRNA; polymorphism