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Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian yaks

Abstract

The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak's hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited 1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding.

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Figure 1: Phylogenetic analyses of sequence data on chromosomes 9 and 25 confirm bovine introgression in the yak that was sequenced to generate the yak reference genome.
Figure 2: Analysis of the size distribution of introgressed intervals in the yak genome reveals three major introgressions events.
Figure 3: Bovine introgressed segments in yaks show a major enrichment for genes related to nervous system development and function.
Figure 4: Introgression of a novel and complex mutation at the POLLED locus from bovines causes polledness in Mongolian yaks.

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Acknowledgements

A.C. acknowledges P. Boudinot and D. Boichard for interesting discussions about the major histocompatibility complex and the recombination rate in cattle, respectively; M. Boussaha, Y. Djari and C. Klopp for introducing him to the use of SAMtools and Pindel software; and M.-C. Deloche, C. Escouflaire and A. Michenet for their punctual assistance. The authors acknowledge the Zoologischer Garten Berlin, Tierpark Cottbus and Tierpark Hellabrunn Munich (Germany), as well as the Jardin des Plantes de Paris (France) and all the breeders in Europe and Asia for generously providing samples and phenotypes. Apis-Gène is acknowledged for funding the AKELOS research project. LAFUGA is funded by the LMU excellence program.

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Contributions

A.C. and I.M. conceived and coordinated the study. A.C., I.M. and S.K. designed the study. I.M. mapped the POLLED locus and performed introgression analysis using SNP chip genotyping data, simulation analyses and neighbor-joining phylogenetic analyses. A.C. performed variant calling, annotation and screening for candidate mutations, analysis of sequence conservation, annotation of the gene content of the introgressed intervals and gene set enrichment analyses. S.K., A.G. and I.M. performed introgression analysis based on WGS data, determination of ancestral alleles, genome and capture sequencing, and R graphics. C.G., S.R. and A.C. performed PCR for Sanger sequencing and for genotyping by PCR and electrophoresis or PCR and Sanger sequencing. J.B. performed WGS. D.S. and I.R. performed SNP chip genotyping and WGS. Y.Z., E.G., N.Z. and G.B. provided samples and phenotypes. H.B. provided sequencing and bioinformatics facilities. A.E. provided Illumina BovineHD SNP chip genotyping data. G.H. provided software and expertise in admixture analysis. A.C., I.M., S.K. and A.G. contributed to writing the manuscript.

Corresponding authors

Correspondence to Ivica Medugorac or Aurélien Capitan.

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The authors declare no competing financial interests.

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Medugorac, I., Graf, A., Grohs, C. et al. Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian yaks. Nat Genet 49, 470–475 (2017). https://doi.org/10.1038/ng.3775

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