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 extant Bos taurus genomes and a single extinct B. primigenius 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 B. taurus and B. primigenius 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 B. taurus and B. 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.

Comparing genomic signatures of domestication in two Atlantic salmon (Salmo salar L.) populations with different geographical origins

“…Therefore, this gene could be involved in muscle development and growth in Atlantic salmon, which is an important trait selected for enhancing salmon aquaculture production. This gene family was also suggested to be potentially involved in immune response of marine vertebrates (Núñez‐Acuña, Aguilar‐Espinoza, Chávez‐Mardones, & Gallardo‐Escárate, ), and more particularly, ubiquitin genes have already been detected to be potential targets of selection in the domestication process of shrimp (Rotllant et al., ), auroch (Braud et al., ) and rice (Li & Li, ). Finally, the autism susceptibility 2 protein‐like (LOC106585083) was also found to overlap between continents.…”

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…Directional selection of miR regulatory variants was important in the domestication and subsequent selection that gave rise to modern taurine cattle. The MIR148A gene has been identified as a candidate of domestication genes of modern cattle [410]. Co-expression network and pathway analyses identified bovine MIR148A as a major determinant enhancing milk yield [411].…”

The evolutionary dynamics of microRNAs in domestic mammals

“…We also looked for positively selected genes Braud et al 2017) in the set of targets of cow specific seed families belonging to a significant GO accession. We found 24 positively selected targets among the 35 common between our set of 1:1 orthologues and the gene list provided by .…”

“…Only 3 targets were found in the gene set from Xu et al ): WIF1 (Increased osteosarcoma incidence), KIT (coat/hair pigmentation) and LRIG3 (Abnormal craniofacial morphology) (2.43 fold under-enrichment, p=2x10e -4 ). Additionally, we considered the dataset from Braud et al (Braud et al 2017), representing genes with high miRNA binding sites divergence between B. taurus and B. primigenius. Among the top 200 scoring genes, we identified 43 targets of cow specific seed families (1.31 fold under-enrichment, p<10e -4 ).…”

“…http://dx.doi.org/10.1101/257006 doi: bioRxiv preprint first posted online Jan. 31, 2018; appears as a positively selected (Freedman et al 2016;Braud et al 2017) target of both dog and cow specific seed families.…”