Recent selection and introgression facilitated high-altitude adaptation in cattle.

During the past 3000 years, cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia, ultraviolet (UV) radiation, and extreme cold. The genetic mechanism underlying this rapid adaptation is not yet well understood. Here, we present whole-genome resequencing data for 258 cattle from 32 cattle breeds/populations, including 89 Tibetan cattle representing eight populations distributed at altitudes ranging from 3400 m to 4300 m. Our genomic analysis revealed that Tibetan cattle exhibited a continuous phylogeographic cline from the East Asian taurine to the South Asian indicine ancestries. We found that recently selected genes in Tibetan cattle were related to body size (HMGA2 and NCAPG) and energy expenditure (DUOXA2). We identified signals of sympatric introgression from yak into Tibetan cattle at different altitudes, covering 0.64%-3.26% of their genomes, which included introgressed genes responsible for hypoxia response (EGLN1), cold adaptation (LRP11), DNA damage repair (LATS1), and UV radiation resistance (GNPAT). We observed that introgressed yak alleles were associated with noncoding variants, including those in present EGLN1. In Tibetan cattle, three yak introgressed SNPs in the EGLN1 promoter region reduced the expression of EGLN1, suggesting that these genomic variants enhance hypoxia tolerance. Taken together, our results indicated complex adaptation processes in Tibetan cattle, where recently selected genes and introgressed yak alleles jointly facilitated rapid adaptation to high-altitude environments.

Local ancestry and selection in admixed Sanjiang cattle.

The majority of native cattle are taurine × indicine cattle of diverse phenotypes in the central region of China. Sanjiang cattle, a typical breed in the central region, play a central role in human livelihood and have good adaptability, including resistance to dampness, heat, roughage, and disease, and are thus regarded as an important genetic resource. However, the genetic history of the successful breed remains unknown. Here, we sequenced 10 Sanjiang cattle genomes and compared them to the 70 genomes of 5 representative populations worldwide. We characterized the genomic diversity and breed formation process of Sanjiang cattle and found that Sanjiang cattle have a mixed ancestry of indicine (55.6%) and taurine (33.2%) dating to approximately 30 generations ago, which has shaped the genome of Sanjiang cattle. Through ancestral fragment inference, selective sweep and transcriptomic analysis, we identified several genes linked to lipid metabolism, immune regulation, and stress reactions across the mosaic genome of Sanjiang cattle showing an excess of taurine or indicine ancestry. Taurine ancestry might contribute to meat quality, and indicine ancestry is more conducive to adaptation to hot climate conditions, making Sanjiang cattle a valuable genetic resource for the central region of China. Our results will help us understand the evolutionary history and ancestry components of Sanjiang cattle, which will provide a reference for resource conservation and selective breeding of Chinese native cattle.

TAS2R16 introgression from banteng into indigenous Chinese cattle.

Historical hybridization between southern indigenous Chinese cattle and banteng has been well-documented and has resulted in gene introgression. Bitter taste receptors were reported in indigenous cattle as a result of introgression from banteng. To determine the level of introgression of the taste 2 receptor member 16 (TAS2R16) gene from banteng into Chinese cattle, two missense mutations in the bovine TAS2R16 gene were examined. Here, we explored the prevalence of the two variants in 28 indigenous Chinese cattle and banteng breeds (comprising 750 individuals) to determine the influence of banteng introgressions on Chinese cattle based on PCR and DNA sequencing. In our study, the two mutant alleles had a higher frequency distribution in southern China with strong geographic distribution, especially in the south-central and southeast areas. In conclusion, this study examines the impact of introgression on the frequency distributions of mutations in variable regions and the subsequent adaptation of Chinese indigenous cattle to different environmental conditions.

A SNP of the COX4I2 gene associated with environmental adaptation in Chinese cattle.

COX4I2 is an isoform of cytochrome C oxidase subunit IV (COX4), which plays an important role in mitochondrial oxidative phosphorylation. This gene affects heat production and thus affects thermoregulatory capacity in mammals. A splice region variant (rs109072064, NC_037340.1:g.61202988C > T) was identified in COX4I2 by using Ensembl, which transforms the amino acid arginine into cysteine in XP_005214921.1. In this study, we sought to determine the relationship between the mutant locus and the environment in which the cattle are located. We verified that mRNA (XM_005214864.4), which translated XP_005214921.1, is expressed in bovine muscle, fat, heart, liver, kidney, lung and testis tissues. The g.61202988C > T variant was then genotyped in 569 individuals of 34 cattle breeds. Compared with the CC genotype, southern cattle carried more the CT and TT genotypes. Furthermore, the association results carried out that the frequencies of genotypes (CC, CT, TT) and the value of climate parameters (mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI)) were significantly correlated (P < 0.01). Hence, we speculated that the g.61202988C > T variant of COX4I2 gene was associated with the environmental adaptation trait in Chinese cattle and the locus may be considered as a molecular marker for Chinese cattle breeding.

Distribution of a missense mutation (rs525805167) within the SLC45A2 gene associated with climatic conditions in Chinese cattle.

SLC45A2 is involved in the synthesis of melanin transporters. We investigated the association between single nucleotide polymorphisms (SNPs) of the SLC45A2 gene and humidity and hot conditions in indigenous cattle habitat. According to the Bovine Genome Variation Database and Selective Signatures (BGVD), we explored the frequency distribution of a missense mutation (NC_037347.1: c.1543A > G, p.ser515gly) in the SLC45A2 gene in Chinese indigenous cattle. This variation from serine to glycine caused a significant change in the protein modeling structure. PCR and partial DNA sequencing were used to genotype 541 individuals, including 28 Chinese indigenous cattle breeds as well as Angus and zebu. From our results, the mutant allele frequency of this SNP in Chinese native cattle increases gradually from north to south, which is consistent with the distribution of climatic conditions in China. In addition, according to association analysis of a missense mutation (NC_037347.1: c.1543A > G) (rs525805167) in Chinese cattle, it is closely related to the annual average temperature (T), relative humidity (RH), temperature and humidity index (THI) and solar radiation time (P < 0.01). Based on the statistical analysis of the data, we assumed that rs525805167 was associated with heat tolerance traits. Simple Summary: The characteristics of Chinese indigenous cattle are closely related to their climatic environment. In China, Bos taurus is mainly distributed in the northern regions; Bos indicus is mainly distributed in southern China. In addition, the average temperature is higher in the south than in the north, and there are many mixed ancestry breeds of B. taurus and B. indicus in the middle area. The SLC45A2 gene is related to melanin synthesis, which may be closely related to heat tolerance in cattle. The purpose of our study was to investigate whether the SLC45A2 gene is related to heat tolerance in Chinese indigenous cattle.