Genome‐wide detection of signatures of selection in Korean Hanwoo cattle

The Korean Hanwoo cattle have been intensively selected for production traits, especially high intramuscular fat content. It is believed that ancient crossings between different breeds contributed to forming the Hanwoo, but little is known about the genomic differences and similarities between other cattle breeds and the Hanwoo. In this work, cattle breeds were grouped by origin into four types and used for comparisons: the Europeans (represented by six breeds), zebu (Nelore), African taurine (N'Dama) and Hanwoo. All animals had genotypes for around 680 000 SNPs after quality control of genotypes. Average heterozygosity was lower in Nelore and N'Dama (0.22 and 0.21 respectively) than in Europeans (0.26–0.31, with Shorthorn as outlier at 0.24) and Hanwoo (0.29). Pairwise F_ST analyses demonstrated that Hanwoo are more related to European cattle than to Nelore, with N'Dama in an intermediate position. This finding was corroborated by principal components and unsupervised hierarchical clustering. Using genome‐wide smoothed F_ST, 55 genomic regions potentially under positive selection in Hanwoo were identified. Among these, 29 were regions also detected in previous studies. Twenty‐four regions were exclusive to Hanwoo, and a number of other regions were shared with one or two of the other groups. These regions overlap a number of genes that are related to immune, reproduction and fatty acid metabolism pathways. Further analyses are needed to better characterize the ancestry of the Hanwoo cattle and to define the genes responsible to the identified selection peaks.     

Whole-genome resequencing analyses of five pig breeds,including Korean wild and native,and three European origin breeds

Pigs have been one of the most important sources of meat for humans, and their productivity has been substantially improved by recent strong selection. Here, we present whole-genome resequencing analyses of 55 pigs of five breeds representing Korean native pigs, wild boar and three European origin breeds. 1,673.1 Gb of sequence reads were mapped to the Swine reference assembly, covering ∼99.2% of the reference genome, at an average of ∼11.7-fold coverage. We detected 20,123,573 single-nucleotide polymorphisms (SNPs), of which 25.5% were novel. We extracted 35,458 of non-synonymous SNPs in 9,904 genes, which may contribute to traits of interest. The whole SNP sets were further used to access the population structures of the breeds, using multiple methodologies, including phylogenetic, similarity matrix, and population structure analysis. They showed clear population clusters with respect to each breed. Furthermore, we scanned the whole genomes to identify signatures of selection throughout the genome. The result revealed several promising loci that might underlie economically important traits in pigs, such as the CLDN1 and TWIST1 genes. These discoveries provide useful genomic information for further study of the discrete genetic mechanisms associated with economically important traits in pigs.     

A genome‐wide scan for selection signatures in Nellore cattle

Brazilian Nellore cattle (Bos indicus) have been selected for growth traits for over more than four decades. In recent years, reproductive and meat quality traits have become more important because of increasing consumption, exports and consumer demand. The identification of genome regions altered by artificial selection can potentially permit a better understanding of the biology of specific phenotypes that are useful for the development of tools designed to increase selection efficiency. Therefore, the aims of this study were to detect evidence of recent selection signatures in Nellore cattle using extended haplotype homozygosity methodology and BovineHD marker genotypes (>777 000 single nucleotide polymorphisms) as well as to identify corresponding genes underlying these signals. Thirty‐one significant regions (P < 0.0001) of possible recent selection signatures were detected, and 19 of these overlapped quantitative trait loci related to reproductive traits, growth, feed efficiency, meat quality, fatty acid profiles and immunity. In addition, 545 genes were identified in regions harboring selection signatures. Within this group, 58 genes were associated with growth, muscle and adipose tissue metabolism, reproductive traits or the immune system. Using relative extended haplotype homozygosity to analyze high‐density single nucleotide polymorphism marker data allowed for the identification of regions potentially under artificial selection pressure in the Nellore genome, which might be used to better understand autozygosity and the effects of selection on the Nellore genome.     

Genetic diversity and genomic signatures of selection among cattle breeds from Siberia,eastern and northern Europe

Domestication in the near eastern region had a major impact on the gene pool of humpless taurine cattle (Bos taurus). As a result of subsequent natural and artificial selection, hundreds of different breeds have evolved, displaying a broad range of phenotypic traits. Here, 10 Eurasian B. taurus breeds from different biogeographic and production conditions, which exhibit different demographic histories and have been under artificial selection at various intensities, were investigated using the Illumina BovineSNP50 panel to understand their genetic diversity and population structure. In addition, we scanned genomes from eight breeds for signatures of diversifying selection. Our population structure analysis indicated six distinct breed groups, the most divergent being the Yakutian cattle from Siberia. Selection signals were shared (experimental P‐value < 0.01) with more than four breeds on chromosomes 6, 7, 13, 16 and 22. The strongest selection signals in the Yakutian cattle were found on chromosomes 7 and 21, where a miRNA gene and genes related to immune system processes are respectively located. In general, genomic regions indicating selection overlapped with known QTL associated with milk production (e.g. on chromosome 19), reproduction (e.g. on chromosome 24) and meat quality (e.g. on chromosome 7). The selection map created in this study shows that native cattle breeds and their genetic resources represent unique material for future breeding.     

Genome‐wide scans to detect positive selection in Large White and Tongcheng pigs

Due to the direction, intensity, duration and consistency of genetic selection, especially recent artificial selection, the production performance of domestic pigs has been greatly changed. Therefore, we reasoned that there must be footprints or selection signatures that had been left during domestication. In this study, with porcine 60K BeadChip genotyping data from both commercial Large White and local Chinese Tongcheng pigs, we calculated the extended haplotype homozygosity values of the two breeds using the long‐range haplotype method to detect selection signatures. We found 34 candidate regions, including 61 known genes, from Large White pigs and 25 regions comprising 57 known genes from Tongcheng pigs. Many selection signatures were found on SSC1, SSC4, SSC7 and SSC14 regions in both populations. According to quantitative trait loci and network pathway analyses, most of the regions and genes were linked to growth, reproduction and immune responses. In addition, the average genetic differentiation coefficient F_ST was 0.254, which means that there had already been a significant differentiation between the breeds. The findings from this study can contribute to further research on molecular mechanisms of pig evolution and domestication and also provide valuable references for improvement of their breeding and cultivation.     

A genome‐wide scan for selection signatures in Yorkshire and Landrace pigs based on sequencing data

Pigs have experienced dramatic selection due to domestication, which has led to many different phenotypes when compared to their wild counterparts, especially in the last several decades. Currently, genome‐wide scans in both cattle and humans showing positive selection footprints have been investigated. However, few studies have focused on porcine selection footprints, particularly on a genome‐wide scale. Surveying for selection footprints across porcine genomes can be quite valuable for revealing the genetic mechanisms of phenotypic diversity. Here, we employed a medium sequencing depth (5–20x/site per individual, on average) approach called genotyping by genome reducing and sequencing (GGRS) to detect genome‐wide selection signatures of two domestic pig breeds (Yorkshire and Landrace) that have been under intensive selection for traits of muscle development, growth and behavior. The relative extended haplotype homozygosity test, which identifies selection signatures by measuring the characteristics of haplotypes’ frequency distribution within a single population, was also applied to identify potential positively selected regions. As a result, signatures of positive selection were found in each breed. However, most selection signatures were population specific and related to genomic regions containing genes for biological categories including brain development, metabolism, growth and olfaction. Furthermore, the result of the gene set enrichment analysis indicated that selected regions of the two breeds presented a different over‐representation of genes in the Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathways. Our results revealed a genome‐wide map of selection footprints in pigs and may help us better understand the mechanisms of selection in pig breeding.     

Genome‐wide analysis reveals artificial selection on coat colour and reproductive traits in Chinese domestic pigs

Pigs from Asia and Europe were independently domesticated from c. 9000 years ago. During this period, strong artificial selection has led to dramatic phenotypic changes in domestic pigs. However, the genetic basis underlying these morphological and behavioural adaptations is relatively unknown, particularly for indigenous Chinese pigs. Here, we performed a genome‐wide analysis to screen 196 regions with selective sweep signals in Tongcheng pigs, which are a typical indigenous Chinese breed. Genes located in these regions have been found to be involved in lipid metabolism, melanocyte differentiation, neural development and other biological processes, which coincide with the evolutionary phenotypic changes in this breed. A synonymous substitution, c.669T>C, in ESR1, which colocalizes with a major quantitative trait locus for litter size, shows extreme differences in allele frequency between Tongcheng pigs and wild boars. Notably, the variant C allele in this locus exhibits high allele frequency in most Chinese populations, suggesting a consequence of positive selection. Five genes (PRM1, PRM2, TNP2, GPR149 and JMJD1C) related to reproductive traits were found to have high haplotype similarity in Chinese breeds. Two selected genes, MITF and EDNRB, are implied to shape the two‐end black colour trait in Tongcheng pig. Subsequent SNP microarray studies of five Chinese white‐spotted breeds displayed a concordant signature at both loci, suggesting that these two genes are responsible for colour variations in Chinese breeds. Utilizing massively parallel sequencing, we characterized the candidate sites that adapt to artificial and environmental selections during the Chinese pig domestication. This study provides fundamental proof for further research on the evolutionary adaptation of Chinese pigs.     

A genome‐wide scan for signatures of recent selection in Holstein cattle

The data from the newly available 50 K SNP chip was used for tagging the genome‐wide footprints of positive selection in Holstein–Friesian cattle. For this purpose, we employed the recently described Extended Haplotype Homozygosity test, which detects selection by measuring the characteristics of haplotypes within a single population. To assess formally the significance of these results, we compared the combination of frequency and the Relative Extended Haplotype Homozygosity value of each core haplotype with equally frequent haplotypes across the genome. A subset of the putative regions showing the highest significance in the genome‐wide EHH tests was mapped. We annotated genes to identify possible influence they have in beneficial traits by using the Gene Ontology database. A panel of genes, including FABP3, CLPN3, SPERT, HTR2A5, ABCE1, BMP4 and PTGER2, was detected, which overlapped with the most extreme P‐values. This panel comprises some interesting candidate genes and QTL, representing a broad range of economically important traits such as milk yield and composition, as well as reproductive and behavioural traits. We also report high values of linkage disequilibrium and a slower decay of haplotype homozygosity for some candidate regions harbouring major genes related to dairy quality. The results of this study provide a genome‐wide map of selection footprints in the Holstein genome, and can be used to better understand the mechanisms of selection in dairy cattle breeding.     

Comparison of microRNAs in adipose and muscle tissue from seven indigenous Chinese breeds and Yorkshire pigs

Elucidation of the pig microRNAome is essential for interpreting functional elements of the genome and understanding the genetic architecture of complex traits. Here, we extracted small RNAs from skeletal muscle and adipose tissue, and we compared their expression levels between one Western breed (Yorkshire) and seven indigenous Chinese breeds. We detected the expression of 172 known porcine microRNAs (miRNAs) and 181 novel miRNAs. Differential expression analysis found 92 and 12 differentially expressed miRNAs in adipose and muscle tissue respectively. We found that different Chinese breeds shared common directional miRNA expression changes compared to Yorkshire pigs. Some miRNAs differentially expressed across multiple Chinese breeds, including ssc‐miR‐129‐5p, ssc‐miR‐30 and ssc‐miR‐150, are involved in adipose tissue function. Functional enrichment analysis revealed that the target genes of the differentially expressed miRNAs are associated mainly with signaling pathways rather than metabolic and biosynthetic processes. The miRNA–target gene and miRNA–phenotypic traits networks identified many hub miRNAs that regulate a large number of target genes or phenotypic traits. Specifically, we found that intramuscular fat content is regulated by the greatest number of miRNAs in muscle tissue. This study provides valuable new candidate miRNAs that will aid in the improvement of meat quality and production.     

Genetic Variation and Association of Insulin-Like Growth Factor Binding Protein-3 with Performance in Swine

Genetic variation of insulin-like growth factor binding protein-3 was analyzed in 17 pig breeds (14 native Chinese and 3 European). Using PCR-single strand conformation polymorphism, we found a polymorphism in intron 2, and this SNP was the combined mutation of G897T-G903A-C911T. The Chinese breeds carried a higher TAT/TAT genotype frequency (over 50%), except for Bamei (22%), Yujiang Black (0.0%), and Erhualian (10.0%); the European breeds had a higher GGC/GGC genotype frequency (Large White 1.67%, Landrace 13.89%, Duroc 0.0%). The allelic frequency of TAT in Chinese breeds was over 50%, except for Yujiang Black (12.5%); the allelic frequency of GGC was over 50% in all European breeds. The effect of genotype on 43 performance traits was investigated in one population (Lantang × Landrace). Pigs with the TAT/TAT genotype had higher B-point and C-point back-fat thickness than pigs with the GGC/GGC genotype. The TAT/TAT pigs also scored higher in meat color than the GGC/GGC pigs. These results implied that IGFBP-3 may affect meat quality and carcass traits.     

Asian low‐androstenone haplotype on pig chromosome 6 does not unfavorably affect production and reproduction traits

European pigs that carry Asian haplotypes of a 1.94‐Mbp region on pig chromosome 6 have lower levels of androstenone, one of the two main compounds causing boar taint. The objective of our study was to examine potential pleiotropic effects of the Asian low‐androstenone haplotypes. A single nucleotide polymorphism marker, rs81308021, distinguishes the Asian from European haplotypes and was used to investigate possible associations of androstenone with production and reproduction traits. Eight traits were available from three European commercial breeds. For the two sow lines studied, a favorable effect on number of teats was detected for the low‐androstenone haplotype. In one of these sow lines, a favorable effect on number of spermatozoa per ejaculation was detected for the low‐androstenone haplotype. No unfavorable pleiotropic effects were found, which suggests that selection for low‐androstenone haplotypes within the 1.94 Mbp would not unfavorably affect the other eight relevant traits.     

Identification of Selection Footprints on the X Chromosome in Pig

Identifying footprints of selection can provide a straightforward insight into the mechanism of artificial selection and further dig out the causal genes related to important traits. In this study, three between-population and two within-population approaches, the Cross Population Extend Haplotype Homozygosity Test (XPEHH), the Cross Population Composite Likelihood Ratio (XPCLR), the F-statistics (Fst), the Integrated Haplotype Score (iHS) and the Tajima''s D, were implemented to detect the selection footprints on the X chromosome in three pig breeds using Illumina Porcine60K SNP chip. In the detection of selection footprints using between-population methods, 11, 11 and 7 potential selection regions with length of 15.62 Mb, 12.32 Mb and 9.38 Mb were identified in Landrace, Chinese Songliao and Yorkshire by XPEHH, respectively, and 16, 13 and 17 potential selection regions with length of 15.20 Mb, 13.00 Mb and 19.21 Mb by XPCLR, 4, 2 and 4 potential selection regions with length of 3.20 Mb, 1.60 Mb and 3.20 Mb by Fst. For within-population methods, 7, 10 and 9 potential selection regions with length of 8.12 Mb, 8.40 Mb and 9.99 Mb were identified in Landrace, Chinese Songliao and Yorkshire by iHS, and 4, 3 and 2 potential selection regions with length of 3.20 Mb, 2.40 Mb and 1.60 Mb by Tajima''s D. Moreover, the selection regions from different methods were partly overlapped, especially the regions around 22 ∼25 Mb were detected under selection in Landrace and Yorkshire while no selection in Chinese Songliao by all three between-population methods. Only quite few overlap of selection regions identified by between-population and within-population methods were found. Bioinformatics analysis showed that the genes relevant with meat quality, reproduction and immune were found in potential selection regions. In addition, three out of five significant SNPs associated with hematological traits reported in our genome-wide association study were harbored in potential selection regions.     

Searching new signals for production traits through gene‐based association analysis in three Italian cattle breeds

Genome‐wide association studies (GWAS) have been widely applied to disentangle the genetic basis of complex traits. In cattle breeds, classical GWAS approaches with medium‐density marker panels are far from conclusive, especially for complex traits. This is due to the intrinsic limitations of GWAS and the assumptions that are made to step from the association signals to the functional variations. Here, we applied a gene‐based strategy to prioritize genotype–phenotype associations found for milk production and quality traits with classical approaches in three Italian dairy cattle breeds with different sample sizes (Italian Brown n = 745; Italian Holstein n = 2058; Italian Simmental n = 477). Although classical regression on single markers revealed only a single genome‐wide significant genotype–phenotype association, for Italian Holstein, the gene‐based approach identified specific genes in each breed that are associated with milk physiology and mammary gland development. As no standard method has yet been established to step from variation to functional units (i.e., genes), the strategy proposed here may contribute to revealing new genes that play significant roles in complex traits, such as those investigated here, amplifying low association signals using a gene‐centric approach.     

Genome‐wide genetic variation discovery in Chinese Taihu pig breeds using next generation sequencing

The Chinese Taihu pig breeds are an invaluable component of the world's pig genetic resources, and they are the most prolific breeds of swine in the world. In this study, the genomes of 252 pigs of the six indigenous breeds in the Taihu Lake region were sequenced using the genotyping by genome reducing and sequencing approach. A total of 950 million good reads were obtained using an Illumina Hiseq2000 at an average depth of 13× (for SNP calling) and an average coverage of 2.3%. In total, 122 632 indels, 31 444 insertions, 44 056 deletions and 455 CNVs (copy number variants) were identified in the genomes of the pigs. Approximately 2.3% of these genetic markers were mapped to gene exon regions, and 25% were in QTL regions related to economically important traits. The KEGG pathway or GO enrichment analyses revealed that genetic variants assumed to be large‐effect mutations were significantly overrepresented in 22 SNP, 56 indel, 26 insertion, 28 deletion and three CNV gene sets. A total of 343 breed‐specific SNPs were also identified in the six Chinese indigenous pigs. The findings from this study can contribute to future investigations of the genetic diversity, population structure, positive selection signals and molecular evolutionary history of these pigs at the genome level and can serve as a valuable reference for improving the breeding and cultivation of these pigs.     

H-FABP、MC4R、ADD1基因多态性在3个猪群中分布及其与肌内脂肪和背膘的相关研究

具有不同遗传特性的猪种具有不同的肉质性状。尤其是地方品种和引进品种间在肉质性状存在极大的差异。在已有的研究中H-FABP,MC4R,ADD1基因同肌内脂肪或背膘相关。利用梅山猪、苏太猪和杜×长×大猪为试验动物,研究上述3个基因的多态性分布和多态性同肌内脂肪和背膘的相关性。结果表明：3个基因的多态性分布在不同猪种间存在极显著的差异,这种差异可能是肌内脂肪（IMF）或背膘（BF）不同的主要原因之一。连锁分析表明：H-FABP和ADD1基因多态性同IMF有显著的相关,但是同BF没有显著的相关;MC4R基因的多态性同IMF和BF都有显著相关性。说明：H-FABP和ADD1基因多态性有可能应用到提高IMF,同时不影响BF的育种实践中。      

Genome‐wide detection of genetic loci and candidate genes for teat number and body conformation traits at birth in Chinese Sushan pigs

Body conformation at birth and teat number are economically important traits in the pig industry, as these traits are usually explored to evaluate the growth and reproductive potential of piglets. To detect genetic loci and candidate genes for these traits, we performed a GWAS on 269 pigs from a recently developed Chinese breed (Sushan) using 38  128 informative SNPs on the Affymetrix Porcine SNP 55K Array. In total, we detected one genome‐wide significant (P = 1.31e‐6) SNP for teat number on chromosome X and 15 chromosome‐wide significant SNPs for teat number, body weight, body length, chest circumference and cannon circumference at birth on chromosomes 1, 3, 4, 6, 7, 9, 10, 13, 14, 15, 17 and 18. The most significant SNP had an additive effect of 0.74 × total teat number, explaining 20% of phenotypic variance. Five significant SNPs resided in the previously reported quantitative trait loci for these traits and seven significant SNPs had a pleiotropic effect on multiple traits. Intriguingly, 12 of the genes nearest to the significant SNPs are functionally related to body conformation and teat number traits, including SPRED2, MKX, TMSB4X and ESR1. GO analysis revealed that candidate genes proximal to the significant SNPs were enriched in the G‐protein coupled receptor and steroid hormone‐mediated signaling pathway. Our findings shed light on the genetic basis of the measured traits and provide molecular markers especially for the genetic improvement of teat number in Sushan and related pigs.     

Detecting selection signatures in three Iranian sheep breeds

The objective of genome mapping is to achieve valuable insight into the connection between gene variants (genotype) and observed traits (phenotype). Part of that objective is to understand the selective forces that have operated on a population. Finding links between genotype–phenotype changes makes it possible to identify selective sweeps by patterns of genetic variation and linkage disequilibrium. Based on Illumina 50KSNP chip data, two approaches, XP‐EHH (cross‐population extend haplotype homozygosity) and F_ST (fixation index), were carried out in this research to identify selective sweeps in the genome of three Iranian local sheep breeds: Baluchi (n = 86), Lori‐Bakhtiari (n = 45) and Zel (n = 45). Using both methods, 93 candidate genomic regions were identified as harboring putative selective sweeps. Bioinformatics analysis of the genomic regions showed that signatures of selection related to multiple candidate genes, such as HOXB9, HOXB13, ACAN, NPR2, TRIL, AOX1, CSF2, GHR, TNS2, SPAG8, HINT2, ALS2, AAAS, RARG, SYCP2, CAV1, PPP1R3D, PLA2G7, TTLL7 and C20orf10, that play a role in skeletal system and tail, sugar and energy metabolisms, growth, reproduction, immune and nervous system traits. Our findings indicated diverse genomic selection during the domestication of Iranian sheep breeds.     

A genome-wide scan for signatures of directional selection in domesticated pigs

Background

Animal 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.

Results

Whole-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.

Conclusions

We 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.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1330-x) contains supplementary material, which is available to authorized users.