IBD sharing patterns as intra-breed admixture indicators in small ruminants.

In this study, we investigated how IBD patterns shared between individuals of the same breed could be informative of its admixture level, with the underlying assumption that the most admixed breeds, i.e. the least genetically isolated, should have a much more fragmented genome. We considered 111 goat breeds (i.e. 2501 individuals) and 156 sheep breeds (i.e. 3304 individuals) from Europe, Africa and Asia, for which beadchip SNP genotypes had been performed. We inferred the breed's level of admixture from: (i) the proportion of the genome shared by breed's members (i.e. "genetic integrity level" assessed from ADMIXTURE software analyses), and (ii) the "AV index" (calculated from Reynolds' genetic distances), used as a proxy for the "genetic distinctiveness". In both goat and sheep datasets, the statistical analyses (comparison of means, Spearman correlations, LM and GAM models) revealed that the most genetically isolated breeds, also showed IBD profiles made up of more shared IBD segments, which were also longer. These results pave the way for further research that could lead to the development of admixture indicators, based on the characterization of intra-breed shared IBD segments, particularly effective as they would be independent of the knowledge of the whole genetic landscape in which the breeds evolve. Finally, by highlighting the fragmentation experienced by the genomes subjected to crossbreeding carried out over the last few generations, the study reminds us of the need to preserve local breeds and the integrity of their adaptive architectures that have been shaped over the centuries.

Natural adaptation and human selection of northeast African sheep genomes.

African sheep manifest diverse but distinct physio-anatomical traits, which are the outcomes of natural- and human-driven selection. Here, we generated 34.8 million variants from 150 indigenous northeast African sheep genomes sequenced at an average depth of ∼54× for 130 samples (Ethiopia, Libya) and ∼20× for 20 samples (Sudan). These represented sheep from diverse environments, tail morphology and post-Neolithic introductions to Africa. Phylogenetic and model-based admixture analysis provided evidence of four genetic groups corresponding to altitudinal geographic origins, tail morphotypes and possible historical introduction and dispersal of the species into and across the continent. Running admixture at higher levels of K (6 ≤ K ≤ 25), revealed cryptic levels of genome intermixing as well as distinct genetic backgrounds in some populations. Comparative genomic analysis identified targets of selection that spanned conserved haplotype structures overlapping clusters of genes and gene families. These were related to hypoxia responses, ear morphology, caudal vertebrae and tail skeleton length, and tail fat-depot structures. Our findings provide novel insights underpinning morphological variation and response to human-driven selection and environmental adaptation in African indigenous sheep.

Genome variation in tick infestation and cryptic divergence in Tunisian indigenous sheep.

BACKGROUND: Ticks are obligate haematophagous ectoparasites considered second to mosquitos as vectors and reservoirs of multiple pathogens of global concern. Individual variation in tick infestation has been reported in indigenous sheep, but its genetic control remains unknown. RESULTS: Here, we report 397 genome-wide signatures of selection overlapping 991 genes from the analysis, using ROH, LR-GWAS, XP-EHH, and FST, of 600 K SNP genotype data from 165 Tunisian sheep showing high and low levels of tick infestations and piroplasm infections. We consider 45 signatures that are detected by consensus results of at least two methods as high-confidence selection regions. These spanned 104 genes which included immune system function genes, solute carriers and chemokine receptor. One region spanned STX5, that has been associated with tick resistance in cattle, implicating it as a prime candidate in sheep. We also observed RAB6B and TF in a high confidence candidate region that has been associated with growth traits suggesting natural selection is enhancing growth and developmental stability under tick challenge. The analysis also revealed fine-scale genome structure indicative of cryptic divergence in Tunisian sheep. CONCLUSIONS: Our findings provide a genomic reference that can enhance the understanding of the genetic architecture of tick resistance and cryptic divergence in indigenous African sheep.

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep.

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

Genomic analysis of 10 years of artificial selection in community-based breeding programs in two Ethiopian indigenous sheep breeds.

In recent times, community-based breeding programs (CBBPs) have been advocated as the best strategy for genetic improvement of local breeds in smallholder farms in developing countries. Since 2009, CBBPs have been implemented for Ethiopian Bonga and Menz sheep to improve growth rates resulting in significant genetic gains in 6-month weights. With the hypothesis that selection could be impacting their genomes, we systematically screened for possible genome changes in the two breeds by analyzing 600K BeadChip genotype data of 151 individuals (with the highest breeding values for 6-month weights) from CBBP flocks against 98 individuals from non-CBBP flocks. We observed no differences in genetic diversity and demographic dynamics between CBBP and non-CBBP flocks. Selection signature analysis employing ROH, logistic regression genome-wide association study , FST , XP-EHH and iHS revealed 5 (Bonga) and 11 (Menz) overlapping regions under selection, that co-localized with QTLs for production (body size/weight, growth, milk yield), meat/milk quality, and health/parasite resistance, suggesting that the decade-long selection has likely started to impact their genomes. However, genome-wide genetic differentiation between the CBBP and non-CBBP flocks is not yet clearly evident.

The maternal origin of indigenous domestic chicken from the Middle East, the north and the horn of Africa.

BACKGROUND: Indigenous domestic chicken represents a major source of protein for agricultural communities around the world. In the Middle East and Africa, they are adapted to hot dry and semi-dry areas, in contrast to their wild ancestor, the Red junglefowl, which lives in humid and sub-humid tropical areas. Indigenous populations are declining following increased demand for poultry meat and eggs, favouring the more productive exotic commercial breeds. In this paper, using the D-loop of mitochondrial DNA as a maternally inherited genetic marker, we address the question of the origin and dispersal routes of domestic chicken of the Middle East (Iraq and Saudi Arabia), the northern part of the African continent (Algeria and Libya) and the Horn of Africa (Ethiopia). RESULTS: The analysis of the mtDNA D-loop of 706 chicken samples from Iraq (n = 107), Saudi Arabia (n = 185), Algeria (n = 88), Libya (n = 23), Ethiopia (n = 211) and Pakistan (n = 92) show the presence of five haplogroups (A, B, C, D and E), suggesting more than one maternal origin for the studied populations. Haplogroup E, which occurred in 625 samples, was the most frequent in all countries. This haplogroup most likely originates from the Indian subcontinent and probably migrated following a terrestrial route to these different countries. Haplotypes belonging to haplogroup D were present in all countries except Algeria and Libya, it is likely a legacy of the Indian Ocean maritime trading network. Haplogroup A was present in all countries and may be of commercial origin. Haplogroup B was found only in Ethiopia. Haplogroup C was only detected in the South-Western region of Saudi Arabia and in Ethiopia. CONCLUSION: The results support a major influence of the Indian subcontinent on the maternal diversity of the today's chicken populations examined here. Most of the diversity occurs within rather than between populations. This lack of phylogeographic signal agrees with both ancient and more recent trading networks having shaped the modern-day diversity of indigenous chicken across populations and countries.

Whole-genome resequencing reveals genomic variation and dynamics in Ethiopian indigenous goats.

Ethiopia has about 52 million indigenous goats with marked phenotypic variability, which is the outcome of natural and artificial selection. Here, we obtained whole-genome sequence data of three Ethiopian indigenous goat populations (Arab, Fellata, and Oromo) from northwestern Ethiopia and analyzed their genome-wide genetic diversity, population structure, and signatures of selection. We included genotype data from four other Ethiopian goat populations (Abergelle, Keffa, Gumuz, and Woyto-Guji) and goats from Asia; Europe; and eastern, southern, western, and northern Africa to investigate the genetic predisposition of the three Ethiopian populations and performed comparative genomic analysis. Genetic diversity analysis showed that Fellata goats exhibited the lowest heterozygosity values (Ho = 0.288 ± 0.005 and He = 0.334 ± 0.0001). The highest values were observed in Arab goats (Ho = 0.310 ± 0.010 and He = 0.347 ± 4.35e-05). A higher inbreeding coefficient (FROH = 0.137 ± 0.016) was recorded for Fellata goats than the 0.105 ± 0.030 recorded for Arab and the 0.112 ± 0.034 recorded for Oromo goats. This indicates that the Fellata goat population should be prioritized in future conservation activities. The three goat populations showed the majority (∼63%) of runs of homozygosity in the shorter (100-150 Kb) length category, illustrating ancient inbreeding and/or small founder effects. Population relationship and structure analysis separated the Ethiopian indigenous goats into two distinct genetic clusters lacking phylogeographic structure. Arab, Fellata, Oromo, Abergelle, and Keffa represented one genetic cluster. Gumuz and Woyto-Guji formed a separate cluster and shared a common genetic background with the Kenyan Boran goat. Genome-wide selection signature analysis identified nine strongest regions spanning 163 genes influencing adaptation to arid and semi-arid environments (HOXC12, HOXC13, HOXC4, HOXC6, and HOXC9, MAPK8IP2), immune response (IL18, TYK2, ICAM3, ADGRG1, and ADGRG3), and production and reproduction (RARG and DNMT1). Our results provide insights into a thorough understanding of genetic architecture underlying selection signatures in Ethiopian indigenous goats in a semi-arid tropical environment and deliver valuable information for goat genetic improvement, conservation strategy, genome-wide association study, and marker-assisted breeding.

Anthropogenic events and responses to environmental stress are shaping the genomes of Ethiopian indigenous goats.

Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. FST, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.

Whole-genome resource sequences of 57 indigenous Ethiopian goats.

Domestic goats are distributed worldwide, with approximately 35% of the one billion world goat population occurring in Africa. Ethiopia has 52.5 million goats, ~99.9% of which are considered indigenous landraces deriving from animals introduced to the Horn of Africa in the distant past by nomadic herders. They have continued to be managed by smallholder farmers and semi-mobile pastoralists throughout the region. We report here 57 goat genomes from 12 Ethiopian goat populations sampled from different agro-climates. The data were generated through sequencing DNA samples on the Illumina NovaSeq 6000 platform at a mean depth of 9.71x and 150 bp pair-end reads. In total, ~2 terabytes of raw data were generated, and 99.8% of the clean reads mapped successfully against the goat reference genome assembly at a coverage of 99.6%. About 24.76 million SNPs were generated. These SNPs can be used to study the population structure and genome dynamics of goats at the country, regional, and global levels to shed light on the species' evolutionary trajectory.

Genetic diversity and within-breed variation in three indigenous Ethiopian sheep based on whole-genome analysis.

The objective of this work was to study genetic diversity by comparing whole genome sequence data of Rutana, Gumuz and Washera sheep found in Amhara and Benishanguel gumuz regional states of Ethiopia. We employed variant calling format tools version 0.1.15 to calculate some genetic diversity indices such as observed heterozygosity, expected heterozygosity, inbreeding coefficient, and nucleotide diversity. The results revealed that, observed heterozygosity ranged from 0.33 in Gumuz to 0.34 in Rutana and Washera sheep. Expected heterozygosity ranged from 0.37 in Rutana to 0.38 in Gumuz and Washera sheep. Expected heterozygosity was found to be higher than observed heterozygosity. Higher inbreeding coefficient (0.12) was recorded for Gumuz sheep compared to 0.09 of Rutana and Washera sheep. Mean nucleotide diversity values were 0.0029, 0.0030 and 0.0028 for Gumuz, Rutana and Washera sheep, respectively. Higher values of nucleotide diversity were recorded. Population structure analysis using principal component analysis revealed no clear separation between Gumuz, Rutana and Washera sheep populations with possibility of gene flow attributed to geographical location proximity. The smaller population size, closed breeding system, genetic drift and uncontrolled (non-random) mating might lead to higher rate of inbreeding in Gumuz, Rutana and Washera sheep, requiring timely intervention. This intervention helps to prevent inbreeding depression and extinction of these valuable breeds of sheep, which helps in sustaining the livelihood of sheep keepers in lowlands and highlands. Nevertheless, the whole-genome analysis revealed high within-breed variation. Uncovered areas of studies like mapping quantitative trait loci, identifying genes underpinning productivity traits such as carcass quantity and meat quality could be carried out on diversified sheep resources identified by the current study. Identifying the genomic regions and biological pathways that contribute to explaining variability in these traits is of great importance for selection purposes. Designing conservation-based within-breed sheep selective breeding programs are recommended considering economically important traits into account.

Genome Divergence and Dynamics in the Thin-Tailed Desert Sheep From Sudan.

With climate change bound to affect food and feed production, emphasis will shift to resilient and adapted indigenous livestock to sustain animal production. However, indigenous livestock comprise several varieties, strains and ecotypes whose genomes are poorly characterized. Here, we investigated genomic variation in an African thin-tailed Desert Sheep sampled in Sudan, using 600K genotype data generated from 92 individuals representing five ecotypes. We included data from 18 fat-tailed and 45 thin-tailed sheep from China, to investigate shared ancestry and perform comparative genomic analysis. We observed a clear genomic differentiation between the African thin-tailed Desert Sheep and the Chinese thin-tailed and fat-tailed sheep, suggesting a broad genetic structure between the fat-tailed and thin-tailed sheep in general, and that at least two autosomal gene pools comprise the genome profile of the thin-tailed sheep. Further analysis detected two distinct genetic clusters in both the African thin-tailed Desert Sheep and the Chinese thin-tailed sheep, suggesting a fine-scale and complex genome architecture in thin-tailed sheep. Selection signature analysis suggested differences in adaptation, production, reproduction and morphology likely underly the fine-scale genetic structure in the African thin-tailed Desert Sheep. This may need to be considered in designing breeding programs and genome-wide association studies.

Whole-Genome Sequence Data Suggest Environmental Adaptation of Ethiopian Sheep Populations.

Great progress has been made over recent years in the identification of selection signatures in the genomes of livestock species. This work has primarily been carried out in commercial breeds for which the dominant selection pressures are associated with artificial selection. As agriculture and food security are likely to be strongly affected by climate change, a better understanding of environment-imposed selection on agricultural species is warranted. Ethiopia is an ideal setting to investigate environmental adaptation in livestock due to its wide variation in geo-climatic characteristics and the extensive genetic and phenotypic variation of its livestock. Here, we identified over three million single nucleotide variants across 12 Ethiopian sheep populations and applied landscape genomics approaches to investigate the association between these variants and environmental variables. Our results suggest that environmental adaptation for precipitation-related variables is stronger than that related to altitude or temperature, consistent with large-scale meta-analyses of selection pressure across species. The set of genes showing association with environmental variables was enriched for genes highly expressed in human blood and nerve tissues. There was also evidence of enrichment for genes associated with high-altitude adaptation although no strong association was identified with hypoxia-inducible-factor (HIF) genes. One of the strongest altitude-related signals was for a collagen gene, consistent with previous studies of high-altitude adaptation. Several altitude-associated genes also showed evidence of adaptation with temperature, suggesting a relationship between responses to these environmental factors. These results provide a foundation to investigate further the effects of climatic variables on small ruminant populations.

Genome-Wide Analysis Revealed Homozygosity and Demographic History of Five Chinese Sheep Breeds Adapted to Different Environments.

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1-5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits (5S_rRNA), the innate and adaptive immune response (HERC2 and CYFIP1), digestion and metabolism (CENPJ), growth (SPP1), body size and developments (GJB2 and GJA3). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia.

Genomic regions subjected to selection frequently show signatures such as within-population reduced nucleotide diversity and outlier values of differentiation among differentially selected populations. In this study, we analyzed 50K SNP genotype data of 373 animals belonging to 23 sheep breeds of different geographic origins using the Rsb (extended haplotype homozygosity) and FST statistical approaches, to identify loci associated with the fat-tail phenotype. We also checked if these putative selection signatures overlapped with regions of high-homozygosity (ROH). The analyses identified novel signals and confirmed the presence of selection signature in genomic regions that harbor candidate genes known to affect fat deposition. Several genomic regions that frequently appeared in ROH were also identified within each breed, but only two ROH islands overlapped with the putative selection signatures. The results reported herein provide the most complete genome-wide study of selection signatures for fat-tail in African and Eurasian sheep breeds; they also contribute insights into the genetic basis for the fat tail phenotype in sheep, and confirm the great complexity of the mechanisms that underlie quantitative traits, such as the fat-tail.

Genome-Wide Variation, Candidate Regions and Genes Associated With Fat Deposition and Tail Morphology in Ethiopian Indigenous Sheep.

Variations in body weight and in the distribution of body fat are associated with feed availability, thermoregulation, and energy reserve. Ethiopia is characterized by distinct agro-ecological and human ethnic farmer diversity of ancient origin, which have impacted on the variation of its indigenous livestock. Here, we investigate autosomal genome-wide profiles of 11 Ethiopian indigenous sheep populations using the Illumina Ovine 50 K SNP BeadChip assay. Sheep from the Caribbean, Europe, Middle East, China, and western, northern and southern Africa were included to address globally, the genetic variation and history of Ethiopian populations. Population relationship and structure analysis separated Ethiopian indigenous fat-tail sheep from their North African and Middle Eastern counterparts. It indicates two main genetic backgrounds and supports two distinct genetic histories for African fat-tail sheep. Within Ethiopian sheep, our results show that the short fat-tail sheep do not represent a monophyletic group. Four genetic backgrounds are present in Ethiopian indigenous sheep but at different proportions among the fat-rump and the long fat-tail sheep from western and southern Ethiopia. The Ethiopian fat-rump sheep share a genetic background with Sudanese thin-tail sheep. Genome-wide selection signature analysis identified eight putative candidate regions spanning genes influencing growth traits and fat deposition (NPR2, HINT2, SPAG8, INSR), development of limbs and skeleton, and tail formation (ALX4, HOXB13, BMP4), embryonic development of tendons, bones and cartilages (EYA2, SULF2), regulation of body temperature (TRPM8), body weight and height variation (DIS3L2), control of lipogenesis and intracellular transport of long-chain fatty acids (FABP3), the occurrence and morphology of horns (RXFP2), and response to heat stress (DNAJC18). Our findings suggest that Ethiopian fat-tail sheep represent a uniquely admixed but distinct genepool that presents an important resource for understanding the genetic control of skeletal growth, fat metabolism and associated physiological processes.