Mitonuclear incompatibility as a hidden driver behind the genome ancestry of African admixed cattle

Abstract

Background Africa is an important watershed in the genetic history of domestic cattle, as two lineages of modern cattle, Bos taurus and B. indicus, form distinct admixed cattle populations. Despite the predominant B. indicus nuclear ancestry of African admixed cattle, B. indicus mitochondria have not been found on the continent. This discrepancy between the mitochondrial and nuclear genomes has been previously hypothesized to be driven by male-biased introgression of Asian B. indicus into ancestral African B. taurus. Given that this hypothesis mandates extreme demographic assumptions relying on random genetic drift, we propose a novel hypothesis of selection induced by mitonuclear incompatibility and assess these hypotheses with regard to the current genomic status of African admixed cattle. Results By analyzing 494 mitochondrial and 235 nuclear genome sequences, we first confirmed the genotype discrepancy between mitochondrial and nuclear genome in African admixed cattle: the absence of B. indicus mitochondria and the predominant B. indicus autosomal ancestry. We applied approximate Bayesian computation (ABC) to assess the posterior probabilities of two selection hypotheses given this observation. The results of ABC indicated that the model assuming both male-biased B. indicus introgression and selection induced by mitonuclear incompatibility explains the current genomic discrepancy most accurately. Subsequently, we identified selection signatures at autosomal loci interacting with mitochondria that are responsible for integrity of the cellular respiration system. By contrast with B. indicus-enriched genome ancestry of African admixed cattle, local ancestries at these selection signatures were enriched with B. taurus alleles, concurring with the key expectation of selection induced by mitonuclear incompatibility. Conclusions Our findings support the current genome status of African admixed cattle as a potential outcome of male-biased B. indicus introgression, where mitonuclear incompatibility exerted selection pressure against B. indicus mitochondria. This study provides a novel perspective on African cattle demography and supports the role of mitonuclear incompatibility in the hybridization of mammalian species.

Genome-wide local ancestry and direct evidence for mitonuclear coadaptation in African hybrid cattle populations (Bos taurus/indicus)

“…Despite extensive admixture, however, all mitochondrial genomes of native African cattle populations analyzed to-date exclusively cluster within the taurine T1 haplogroup (Bradley et al, 1996; Kwon et al, 2022; Loftus et al, 1994a; Loftus et al, 1994b; Troy et al, 2001). This observation, together with the widespread distribution of B. indicus Y-chromosome haplotypes across Africa (Hanotte et al, 2000; Perez-Pardal et al, 2018), has been interpreted as the result of human-mediated dispersal and breeding of zebu bulls from South Asia during the last three millennia (Hanotte et al, 2002; Hanotte et al ., 2000; MacHugh et al, 1997; Perez-Pardal et al ., 2018).…”

“…Fixation of the T1 haplogroup in African cattle has been investigated recently. An approximate Bayesian computation (ABC) approach using genome-wide nuclear SNP data from 162 East African cattle indicated that a model of male-mediated dispersal combined with mitonuclear interactions could explain current patterns of bovine genomic diversity in this region (Kwon et al ., 2022). Here, we examine continent-wide discordance of uniparental and biparental genomic variation in African cattle and test the hypothesis that functional incompatibilities have arisen between the mitochondrial and nuclear genomes in hybrid cattle populations across the continent (Figure 1).…”

Genome-wide local ancestry and evidence for mitonuclear coadaptation in African hybrid cattle populations

“…Despite extensive admixture, however, all mitochondrial genomes of native African cattle populations analyzed to date exclusively cluster within the taurine T1 haplogroup ( Bradley et al., 1996 ; Kwon et al., 2022 ; Loftus et al., 1994a , 1994b ; Troy et al., 2001 ). This observation, together with the widespread distribution of B. indicus Y chromosome haplotypes across Africa ( Hanotte et al., 2000 ; Perez-Pardal et al., 2018 ), has been interpreted as the result of human-mediated dispersal and breeding of zebu bulls from South Asia during the last three millennia ( Hanotte et al., 2000 , 2002 ; MacHugh et al., 1997 ; Perez-Pardal et al., 2018 ).…”

“…Functional mismatches between the mitochondrial and nuclear genomes transmitted from two divergent parental lineages have been observed in many vertebrate populations ( Hill, 2019 ; Hill et al., 2019 ). For example, recent studies on hybridization in cattle, hares, sparrows, and hominids have provided compelling evidence for mitonuclear incompatibilities ( Kwon et al., 2022 ; Seixas et al., 2018 ; Sharbrough et al., 2017 ; Trier et al., 2014 ). These likely stem from the fact that the 37 genes located in vertebrate mitochondrial genomes ( Boore, 1999 ) also rely on over one thousand coadapted nuclear genes that encode proteins and protein subunits essential to the efficient functioning of the mitochondrion ( Blier et al., 2001 ; Rand et al., 2004 ; Sloan et al., 2018 ; Woodson and Chory, 2008 ).…”

“…Fixation of the T1 haplogroup in African cattle has been investigated recently. An approximate Bayesian computation approach using genome-wide nuclear SNP data from 162 East African cattle indicated that a model of male-mediated dispersal combined with mitonuclear interactions could explain the current patterns of bovine genomic diversity in this region ( Kwon et al., 2022 ). Here, we examine discordance of uniparental and biparental genomic variation in African cattle and test the hypothesis that functional incompatibilities have arisen between the mitochondrial and nuclear genomes in hybrid cattle populations across the continent ( Figure 1 ).…”