Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases.
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ABSTRACT:
SUBMITTER: Amato R
PROVIDER: S-EPMC2775949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The genetic differentiation of the current horse population was evolutionarily created by natural or artificial selection which shaped the genomes of individual breeds in several unique ways. The availability of high throughput genotyping methods created the opportunity to study this genetic variation on a genome-wide level allowing detection of genome regions divergently selected between separate breeds as well as among different horse types sharing similar phenotypic features. In this study, we used the population differentiation index (FST) that is generally used for measuring locus-specific allele frequencies variation between populations, to detect selection signatures among six horse breeds maintained in Poland. These breeds can be classified into three major categories, including light, draft and primitive horses, selected mainly in terms of type (utility), exterior, performance, size, coat color and appearance. The analysis of the most pronounced selection signals found in this study allowed us to detect several genomic regions and genes connected with processes potentially important for breed phenotypic differentiation and associated with energy homeostasis during physical effort, heart functioning, fertility, disease resistance and motor coordination. Our results also confirmed previously described association of loci on ECA3 (spanning LCORL and NCAPG genes) and ECA11 (spanning LASP1 gene) with the regulation of body size in our draft and primitive (small size) horses. The efficiency of the applied FST-based approach was also confirmed by the identification of a robust selection signal in the blue dun colored Polish Konik horses at the locus of TBX3 gene, which was previously shown to be responsible for dun coat color dilution in other horse breeds. FST-based method showed to be efficient in detection of diversifying selection signatures in the analyzed horse breeds. Especially pronounced signals were observed at the loci responsible for fixed breed-specific features. Several candidate genes under selection were proposed in this study for traits selected in separate breeds and horse types, however, further functional and comparative studies are needed to confirm and explain their effect on the observed genetic diversity of the horse breeds.
| S-EPMC6353161 | biostudies-literature
Project description:BackgroundAnimal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication.ResultsWhole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness.ConclusionsWe show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.
| S-EPMC4349229 | biostudies-literature
Project description:BACKGROUND: Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH). RESULTS: We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content. CONCLUSIONS: These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and marbling score in Korean beef cattle. Based on the confirmation process and literature search we deduce that XP-EHH is able to uncover numerous artificial selection targets in subpopulations of domesticated animals.
| S-EPMC3878089 | biostudies-other
Project description:BackgroundNatural and anthropogenic disasters can have long-lasting impacts on the genetics and structure of impacted populations. The 1986 Chernobyl Nuclear Power Plant disaster led to extensive contamination of the local environment and the wildlife therein. Several ecological, environmental, and genetic studies reported various effects of this disaster on animal, insect, and plant species; however, little work has been done to investigate the genetics of the free-breeding dogs that occupy the Chernobyl Exclusion Zone (CEZ).ResultsWe define the population genetic structure of two groups of dogs that reside within the CEZ, one around the reactor site itself and another living within Chernobyl City. We found little evidence of gene flow and a significant degree of genetic differentiation between the two populations dogs, suggesting that these are two distinct populations despite occupying areas located just 16 km apart. With an FST-based outlier analysis, we then performed a genome-wide scan for evidence of directional selection within the dog populations. We found 391 outlier loci associated with genomic regions influenced by directional selection, from which we identified 52 candidate genes.ConclusionsOur genome scan highlighted outlier loci within or near genomic regions under directional selection, possibly in response to the multi-generational exposure faced. In defining the population structure and identifying candidate genes for these dog populations, we take steps towards understanding how these types of prolonged exposures have impacted these populations.
| S-EPMC9993684 | biostudies-literature
Project description:BackgroundIdentification of genomic regions that have been targets of selection may shed light on the genetic history of livestock populations and help to identify variation controlling commercially important phenotypes. The Azeri and Kuzestani buffalos are the most common indigenous Iranian breeds which have been subjected to divergent selection and are well adapted to completely different regions. Examining the genetic structure of these populations may identify genomic regions associated with adaptation to the different environments and production goals.ResultsA set of 385 water buffalo samples from Azeri (N = 262) and Khuzestani (N = 123) breeds were genotyped using the Axiom® Buffalo Genotyping 90 K Array. The unbiased fixation index method (FST) was used to detect signatures of selection. In total, 13 regions with outlier FST values (0.1%) were identified. Annotation of these regions using the UMD3.1 Bos taurus Genome Assembly was performed to find putative candidate genes and QTLs within the selected regions. Putative candidate genes identified include FBXO9, NDFIP1, ACTR3, ARHGAP26, SERPINF2, BOLA-DRB3, BOLA-DQB, CLN8, and MYOM2.ConclusionsCandidate genes identified in regions potentially under selection were associated with physiological pathways including milk production, cytoskeleton organization, growth, metabolic function, apoptosis and domestication-related changes include immune and nervous system development. The QTL identified are involved in economically important traits in buffalo related to milk composition, udder structure, somatic cell count, meat quality, and carcass and body weight.
| S-EPMC5996463 | biostudies-literature
Project description:Lueyang black-bone chicken is a domestic breed in China. The genetic mechanism of the formation of important economic traits of this breed has not been studied systematically. Therefore, in this study, whole genome resequencing was used to systematically analyze and evaluate the genetic diversity of the black-feather and white-feather populations, and to screen and identify key genes related to phenotypes. The results of principal component analysis and population structure analysis showed that Lueyang black-feathered chickens and white-feathered chickens could be divided into 2 subgroups, and the genetic diversity of black-feathered chicken was richer than that of white-feathered chickens. Linkage disequilibrium analysis also showed that the selection intensity of black-feathered chickens was lower than for white-feathered chickens, which was mainly due to the small population size of white-feathered chickens and a certain degree of inbreeding. Fixation index (FST) analysis revealed that the candidate genes related to feather color traits were G-gamma, FA, FERM, Kelch, TGFb, Arf, FERM, and melanin synthesis-related gene tyrosinase (TYR). Based on Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Jak-STAT, mTOR, and TGF-β signaling pathways were mainly related to melanogenesis and plume color. The findings of this study supported important information for the evaluation and protection of chicken genetic resources and help to analyze the unique genetic phenotypes such as melanin deposition and feather color of Lueyang black-bone chicken. Additionally, it could provide basic research data for the improvement and breeding of Lueyang black-bone chicken with characteristic traits.
| S-EPMC10199218 | biostudies-literature
Project description:High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.
| S-EPMC2936536 | biostudies-literature
Project description:Elucidation of natural selection signatures and relationships with phenotype spectra is important to understand adaptive evolution of modern humans. Here, we conducted a genome-wide scan of selection signatures of the Japanese population by estimating locus-specific time to the most recent common ancestor using the ascertained sequentially Markovian coalescent (ASMC), from the biobank-based large-scale genome-wide association study data of 170,882 subjects. We identified 29 genetic loci with selection signatures satisfying the genome-wide significance. The signatures were most evident at the alcohol dehydrogenase (ADH) gene cluster locus at 4q23 (PASMC = 2.2 × 10-36), followed by relatively strong selection at the FAM96A (15q22), MYOF (10q23), 13q21, GRIA2 (4q32), and ASAP2 (2p25) loci (PASMC < 1.0 × 10-10). The additional analysis interrogating extended haplotypes (integrated haplotype score) showed robust concordance of the detected signatures, contributing to fine-mapping of the genes, and provided allelic directional insights into selection pressure (e.g., positive selection for ADH1B-Arg48His and HLA-DPB1*04:01). The phenome-wide selection enrichment analysis with the trait-associated variants identified a variety of the modern human phenotypes involved in the adaptation of Japanese. We observed population-specific evidence of enrichment with the alcohol-related phenotypes, anthropometric and biochemical clinical measurements, and immune-related diseases, differently from the findings in Europeans using the UK Biobank resource. Our study demonstrated population-specific features of the selection signatures in Japanese, highlighting a value of the natural selection study using the nation-wide biobank-scale genome and phenotype data.
| S-EPMC7182208 | biostudies-literature
Project description:BackgroundModern breeding and artificial selection play critical roles in pig domestication and shape the genetic variation of different breeds. China has many indigenous pig breeds with various characteristics in morphology and production performance that differ from those of foreign commercial pig breeds. However, the signatures of selection on genes implying for economic traits between Chinese indigenous and commercial pigs have been poorly understood.ResultsWe identified footprints of positive selection at the whole genome level, comprising 44,652 SNPs genotyped in six Chinese indigenous pig breeds, one developed breed and two commercial breeds. An empirical genome-wide distribution of Fst (F-statistics) was constructed based on estimations of Fst for each SNP across these nine breeds. We detected selection at the genome level using the High-Fst outlier method and found that 81 candidate genes show high evidence of positive selection. Furthermore, the results of network analyses showed that the genes that displayed evidence of positive selection were mainly involved in the development of tissues and organs, and the immune response. In addition, we calculated the pairwise Fst between Chinese indigenous and commercial breeds (CHN VS EURO) and between Northern and Southern Chinese indigenous breeds (Northern VS Southern). The IGF1R and ESR1 genes showed evidence of positive selection in the CHN VS EURO and Northern VS Southern groups, respectively.ConclusionsIn this study, we first identified the genomic regions that showed evidences of selection between Chinese indigenous and commercial pig breeds using the High-Fst outlier method. These regions were found to be involved in the development of tissues and organs, the immune response, growth and litter size. The results of this study provide new insights into understanding the genetic variation and domestication in pigs.
| S-EPMC3898232 | biostudies-literature
Project description:BackgroundVarious regions of the chicken genome have been under natural and artificial selection for thousands of years. The substantial diversity that exits among chickens from different geographic regions provides an excellent opportunity to investigate the genomic regions under selection which, in turn, will increase our knowledge about the mechanisms that underlie chicken diversity and adaptation. Several statistics have been developed to detect genomic regions that are under selection. In this study, we applied approaches based on differences in allele or haplotype frequencies (FST and hapFLK, respectively) between populations, differences in long stretches of consecutive homozygous sequences (ROH), and differences in allele frequencies within populations (composite likelihood ratio (CLR)) to identify inter- and intra-populations traces of selection in two Iranian indigenous chicken ecotypes, the Lari fighting chicken and the Khazak or creeper (short-leg) chicken.ResultsUsing whole-genome resequencing data of 32 individuals from the two chicken ecotypes, approximately 11.9 million single nucleotide polymorphisms (SNPs) were detected and used in genomic analyses after quality processing. Examination of the distribution of ROH in the two populations indicated short to long ROH, ranging from 0.3 to 5.4 Mb. We found 90 genes that were detected by at least two of the four applied methods. Gene annotation of the detected putative regions under selection revealed candidate genes associated with growth (DCN, MEOX2 and CACNB1), reproduction (ESR1 and CALCR), disease resistance (S1PR1, ALPK1 and MHC-B), behavior pattern (AGMO, GNAO1 and PSEN1), and morphological traits (IHH and NHEJ1).ConclusionsOur findings show that these two phenotypically different indigenous chicken populations have been under selection for reproduction, immune, behavioral, and morphology traits. The results illustrate that selection can play an important role in shaping signatures of differentiation across the genomic landscape of two chicken populations.
| S-EPMC8428137 | biostudies-literature