Inference of Admixture Origins in Indigenous African Cattle.

Present-day African cattle retain a unique genetic profile composed of a mixture of the Bos taurus and Bos indicus populations introduced into the continent at different time periods. However, details of the admixture history and the exact origins of the source populations remain obscure. Here, we infer the source of admixture in the earliest domestic cattle in Africa, African taurine. We detect a significant contribution (up to ∼20%) from a basal taurine lineage, which might represent the now-extinct African aurochs. In addition, we show that the indicine ancestry of African cattle, although most closely related to so-far sampled North Indian indicine breeds, has a small amount of additional genetic affinity to Southeast Asian indicine breeds. Our findings support the hypothesis of aurochs introgression into African taurine and generate a novel hypothesis that the origin of indicine ancestry in Africa might be different indicine populations than the ones found in North India today.

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

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.

Whole-genome resequencing reveals selection signatures associated with milk production traits in African Kenana dairy zebu cattle.

Milk production and composition are the most economically important traits affecting profitability in dairy cattle. In this study, we aimed at detecting signatures of positive selection in Kenana, known as one of the high milk production African indigenous zebu cattle, using next-generation sequencing data. To detect genomic signatures of positive selection, we applied three methods based on population comparison, fixation index (FST), cross population composite likelihood ratio (XP-CLR) and nucleotide diversity (Pi). Further analysis showed that several candidate genes such as CSN3, IGFBP-2, RORA, ABCG2, B4GALT1 and GHR are positively selected for milk production traits in Kenana cattle. The candidate genes and enriched pathways identified in this study may provide a basis for future genome-wide association studies and investigations into genomic targets of selection in dairy cattle.

Whole genome scan reveals the genetic signature of African Ankole cattle breed and potential for higher quality beef.

BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods. RESULTS: We identified 238 (XP-EHH) and 213 (XP-CLR) positively selected genes, of which 97 were detected from both statistics. Among the genes obtained, we primarily reported those involved in different biological process and pathways associated with meat quality traits. Genes (CAPZB, COL9A2, PDGFRA, MAP3K5, ZNF410, and PKM2) involved in muscle structure and metabolism affect meat tenderness. Genes (PLA2G2A, PARK2, ZNF410, MAP2K3, PLCD3, PLCD1, and ROCK1) related to intramuscular fat (IMF) are involved in adipose metabolism and adipogenesis. MB and SLC48A1 affect meat color. In addition, we identified genes (TIMP2, PKM2, PRKG1, MAP3K5, and ATP8A1) related to feeding efficiency. Among the enriched Gene Ontology Biological Process (GO BP) terms, actin cytoskeleton organization, actin filament-based process, and protein ubiquitination are associated with meat tenderness whereas cellular component organization, negative regulation of actin filament depolymerization and negative regulation of protein complex disassembly are involved in adipocyte regulation. The MAPK pathway is responsible for cell proliferation and plays an important role in hyperplastic growth, which has a positive effect on meat tenderness. CONCLUSION: Results revealed several candidate genes positively selected in Ankole cattle in relation to meat quality characteristics. The genes identified are involved in muscle structure and metabolism, and adipose metabolism and adipogenesis. These genes help in the understanding of the biological mechanisms controlling beef quality characteristics in African Ankole cattle. These results provide a basis for further research on the genomic characteristics of Ankole and other Sanga cattle breeds for quality beef.

Tropically adapted cattle of Africa: perspectives on potential role of copy number variations.

Africa is host to diverse and locally adapted cattle breeds that are expected to survive the harsh and extreme tropical environments associated with diseases and parasite infections, heat stress and episodes of feed and water scarcity. Genomic copy number variations (CNVs) are considered to be primary role players in cattle breed formation and adaptation where isolation and genetic drift together with subsequent mutations have created an enormous diversity of local populations. CNVs are modifications in DNA structure comprising deletions, duplications and insertions that are >1 kb in size. Despite attracting much attention, the frequency and pattern of bovine CNV events, especially in African cattle breeds, are for the most part largely unknown. Characterization of genetic variation in the indigenous cattle of Africa will be a vital step toward dissecting the molecular mechanisms underlying phenotypic variation and local adaptation. This review therefore aims to describe the current knowledge regarding bovine CNVs and the implications and potentials they encompass for dissecting genetic adaptation and the genotypic skeleton of tropical African cattle populations.

Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle.

The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10-7 and p < 1.89 × 10-7, respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens.

Population Structure Assessed Using Microsatellite and SNP Data: An Empirical Comparison in West African Cattle.

A sample of 185 West African cattle belonging to nine different taurine, sanga, and zebu populations was typed using a set of 33 microsatellites and the BovineHD BeadChip of Illumina. The information provided by each type of marker was summarized via clustering methods and principal component analyses (PCA). The aim was to assess differences in performance between both marker types for the identification of population structure and the projection of genetic variability on geographical maps. In general, both microsatellites and Single Nucleotide Polymorphism (SNP) allowed us to differentiate taurine cattle from zebu and sanga cattle, which, in turn, would form a single population. Pearson and Spearman correlation coefficients computed among the admixture coefficients (fitting K = 2) and the eigenvectors corresponding to the first two factors identified using PCA on both microsatellite and SNP data were statistically significant (most of them having p < 0.0001) and high. However, SNP data allowed for a better fine-scale identification of population structure within taurine cattle: Lagunaire cattle from Benin were separated from two different N'Dama cattle samples. Furthermore, when clustering analyses assumed the existence of two parental populations only (K = 2), the SNPs could differentiate a different genetic background in Lagunaire and N'Dama cattle. Although the two N'Dama cattle populations had very different breeding histories, the microsatellite set could not separate the two N'Dama cattle populations. Classic bidimensional dispersion plots constructed using factors identified via PCA gave different shapes for microsatellites and SNPs: plots constructed using microsatellite polymorphism would suggest the existence of weakly differentiated, highly intermingled, subpopulations. However, the projection of the factors identified on synthetic maps gave comparable images. This would suggest that results on population structuring must be interpreted with caution. The geographic projection of genetic variation on synthetic maps avoids interpretations that go beyond the results obtained, particularly when previous information on the analyzed populations is scant. Factors influencing the performance of the projection of genetic parameters on geographic maps, together with restrictions that may affect the election of a given type of markers, are discussed.

Inference of Ancestries and Heterozygosity Proportion and Genotype Imputation in West African Cattle Populations.

Several studies have evaluated computational methods that infer the haplotypes from population genotype data in European cattle populations. However, little is known about how well they perform in African indigenous and crossbred populations. This study investigates: (1) global and local ancestry inference; (2) heterozygosity proportion estimation; and (3) genotype imputation in West African indigenous and crossbred cattle populations. Principal component analysis (PCA), ADMIXTURE, and LAMP-LD were used to analyse a medium-density single nucleotide polymorphism (SNP) dataset from Senegalese crossbred cattle. Reference SNP data of East and West African indigenous and crossbred cattle populations were used to investigate the accuracy of imputation from low to medium-density and from medium to high-density SNP datasets using Minimac v3. The first two principal components differentiated Bos indicus from European Bos taurus and African Bos taurus from other breeds. Irrespective of assuming two or three ancestral breeds for the Senegalese crossbreds, breed proportion estimates from ADMIXTURE and LAMP-LD showed a high correlation (r ≥ 0.981). The observed ancestral origin heterozygosity proportion in putative F1 crosses was close to the expected value of 1.0, and clearly differentiated F1 from all other crosses. The imputation accuracies (estimated as correlation) between imputed and the real data in crossbred animals ranged from 0.142 to 0.717 when imputing from low to medium-density, and from 0.478 to 0.899 for imputation from medium to high-density. The imputation accuracy was generally higher when the reference data came from the same geographical region as the target population, and when crossbred reference data was used to impute crossbred genotypes. The lowest imputation accuracies were observed for indigenous breed genotypes. This study shows that ancestral origin heterozygosity can be estimated with high accuracy and will be far superior to the use of observed individual heterozygosity for estimating heterosis in African crossbred populations. It was not possible to achieve high imputation accuracy in West African crossbred or indigenous populations based on reference data sets from East Africa, and population-specific genotyping with high-density SNP assays is required to improve imputation.

Corrigendum: Genetic Diversity of Seven Cattle Breeds Inferred Using Copy Number Variations.

[This corrects the article DOI: 10.3389/fgene.2018.00163.].

Genetic Diversity of Seven Cattle Breeds Inferred Using Copy Number Variations.

Copy number variations (CNVs) comprise deletions, duplications, and insertions found within the genome larger than 50 bp in size. CNVs are thought to be primary role-players in breed formation and adaptation. South Africa boasts a diverse ecology with harsh environmental conditions and a broad spectrum of parasites and diseases that pose challenges to livestock production. This has led to the development of composite cattle breeds which combine the hardiness of Sanga breeds and the production potential of the Taurine breeds. The prevalence of CNVs within these respective breeds of cattle and the prevalence of CNV regions (CNVRs) in their diversity, adaptation and production is however not understood. This study therefore aimed to ascertain the prevalence, diversity, and correlations of CNVRs within cattle breeds used in South Africa. Illumina Bovine SNP50 data and PennCNV were utilized to identify CNVRs within the genome of 287 animals from seven cattle breeds representing Sanga, Taurine, Composite, and cross breeds. Three hundred and fifty six CNVRs of between 36 kb to 4.1 Mb in size were identified. The null hypothesis that one CNVR loci is independent of another was tested using the GENEPOP software. One hunded and two and seven of the CNVRs in the Taurine and Sanga/Composite cattle breeds demonstrated a significant (p ≤ 0.05) association. PANTHER overrepresentation analyses of correlated CNVRs demonstrated significant enrichment of a number of biological processes, molecular functions, cellular components, and protein classes. CNVR genetic variation between and within breed group was measured using phiPT which allows intra-individual variation to be suppressed and hence proved suitable for measuring binary CNVR presence/absence data. Estimate PhiPT within and between breed variance was 2.722 and 0.518 respectively. Pairwise population PhiPT values corresponded with breed type, with Taurine Holstein and Angus breeds demonstrating no between breed CNVR variation. Phylogenetic trees were drawn. CNVRs primarily clustered animals of the same breed type together. This study successfully identified, characterized, and analyzed 356 CNVRs within seven cattle breeds. CNVR correlations were evident, with many more correlations being present among the exotic Taurine breeds. CNVR genetic diversity of Sanga, Taurine and Composite breeds was ascertained with breed types exposed to similar selection pressures demonstrating analogous incidences of CNVRs.

The genome landscape of indigenous African cattle.

BACKGROUND: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. RESULTS: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/or pathways controlling anemia and feeding behavior in the trypanotolerant N'Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. CONCLUSIONS: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent.

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study.

Signatures of Selection for Environmental Adaptation and Zebu × Taurine Hybrid Fitness in East African Shorthorn Zebu.

The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ samples from Kenya (KEASZ) with more than 770,000 SNPs and sequenced the genome of a pool of 10 KEASZ. We observe an even admixed autosomal zebu × taurine genomic structure in the population. A total of 101 and 165 candidate regions of positive selection, based on genome-wide SNP analyses (meta-SS, Rsb, iHS, and ΔAF) and pooled heterozygosity (Hp) full genome sequence analysis, are identified, in which 35 regions are shared between them. A total of 142 functional variants, one novel, have been detected within these regions, in which 30 and 26 were classified as of zebu and African taurine origins, respectively. High density genome-wide SNP analysis of zebu × taurine admixed cattle populations from Uganda and Nigeria show that 25 of these regions are shared between KEASZ and Uganda cattle, and seven regions are shared across the KEASZ, Uganda, and Nigeria cattle. The identification of common candidate regions allows us to fine map 18 regions. These regions intersect with genes and QTL associated with reproduction and environmental stress (e.g., immunity and heat stress) suggesting that the genome of the zebu × taurine admixed cattle has been uniquely selected to maximize hybrid fitness both in terms of reproduction and survivability.