Genome-Wide microRNA Binding Site Variation between Extinct Wild Aurochs and Modern Cattle Identifies Candidate microRNA-Regulated Domestication Genes

The domestication of cattle from the now-extinct wild aurochs ( ) 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...

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Published in:Frontiers in genetics Vol. 8; p. 3
Main Authors: Braud, Martin, Magee, David A., Park, Stephen D. E., Sonstegard, Tad S., Waters, Sinead M., MacHugh, David E., Spillane, Charles
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 31.01.2017
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ISSN:1664-8021, 1664-8021
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Summary:The domestication of cattle from the now-extinct wild aurochs ( ) 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 extant genomes and a single extinct genome. 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 the and lineages 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 from and 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.
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Edited by: Martien Groenen, Wageningen University and Research Centre, Netherlands
Reviewed by: Dan Nonneman, Agricultural Research Service (USDA), USA; Laurent Frantz, University of Oxford, UK
This article was submitted to Livestock Genomics, a section of the journal Frontiers in Genetics
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2017.00003