Deleterious protein-coding variants in diverse cattle breeds of the world

Abstract

The domestication of wild animals has resulted in a reduction in effective population sizes, which can affect the deleterious mutation load of domesticated breeds. In addition, artificial selection contributes to the accumulation of deleterious mutations because of an increased rate of inbreeding among domesticated animals. Since founder population sizes and artificial selection differ between cattle breeds, their deleterious mutation load can vary. We investigated this question by using whole-genome data from 432 animals belonging to 54 worldwide cattle breeds. Our analysis revealed a negative correlation between genomic heterozygosity and nonsynonymous-to-silent diversity ratio, which suggests a higher proportion of single nucleotide variants (SNVs) affecting proteins in low-diversity breeds. Our results also showed that low-diversity breeds had a larger number of high-frequency (derived allele frequency (DAF) > 0.51) deleterious SNVs than high-diversity breeds. An opposite trend was observed for the low-frequency (DAF ≤ 0.51) deleterious SNVs. Overall, the number of high-frequency deleterious SNVs was larger in the genomes of taurine cattle breeds than of indicine breeds, whereas the number of low-frequency deleterious SNVs was larger in the genomes of indicine cattle than in those of taurine cattle. Furthermore, we observed significant variation in the counts of deleterious SNVs within taurine breeds. The variations in deleterious mutation load between taurine and indicine breeds could be attributed to the population sizes of the wild progenitors before domestication, whereas the variations observed within taurine breeds could be due to differences in inbreeding level, strength of artificial selection, and/or founding population size. Our findings imply that the incidence of genetic diseases can vary between cattle breeds.

Deleterious mutation load in the admixed mice population

“…Similar results were reported by comparing the exomes of domesticated and wild yaks (Xie et al, 2018). Using 432 animals belonging to 54 worldwide cattle breeds, a previous study found a negative correlation between heterozygosity and deleterious mutational load, which suggests that breeds that have low genetic variation have higher deleterious mutational load than those with high genetic variation (Subramanian, 2021). Since heterozygosity is the product of N e and mutation rate (μ), and the mutation rate is largely similar across breeds, the above relationship implies a negative correlation between N e and the mutation load.…”

Genomic signatures of bottleneck and founder effects in dingoes

“…Previous studies showed that the dN/dS ratios for domesticated animals such as dog, cow, yak, pig, and silkworm and plants such as rice, soybean, and sunflower were significantly higher than those of their wild counterparts (Lu, et al 2006;Mezmouk and Ross-Ibarra 2014;Renaut and Rieseberg 2015;Kono, et al 2016;Pedersen, et al 2017;Ramu, et al 2017;Makino, et al 2018;Peischl, et al 2018;Xie, et al 2018;Bosse, et al 2019;Robinson, et al 2019;Nicolas Dussex 2021;Subramanian 2021). Furthermore, domesticated plants and animals were found to have more homozygous deleterious SNVs than their wild relatives Xie, et al 2018;Subramanian 2021).…”

“…Reduction in population size was also known to increase the frequencies of rare deleterious variants, and hence the number of homozygous SNVs is expected to be high in bottlenecked populations. Indeed, significantly higher numbers of homozygous nonsynonymous SNVs are frequently reported in small or bottlenecked populations (Marsden, et al 2016; Xie, et al 2018; Subramanian 2021). Studies of bottlenecked populations also observe an abundance of homozygous SNVs that were predicted to be deleterious based on their functional consequences or evolutionary constraints.…”

Comparative transcriptome in large-scale human and cattle populations

“…Cattle is one of the most economically important livestock species, supplying humans with a substantial fraction of animal protein. Driven by the high selection intensity of economically important traits, compared to humans, cattle has a different population structure, such as smaller effective population size (Ne ~100), higher linkage disequilibrium (LD) among genomic variants, and higher inbreeding rate (i.e., resulting in the accumulation of deleterious mutations) [ 6 ]. Furthermore, millions of highly accurate phenotypic records, including fertility, health, and growth traits, have been collected for cattle [ 7 , 8 ].…”