Signatures of selection? Patterns of microsatellite diversity on a chromosome containing a selected locus

This paper explores patterns of genetic diversity near a locus known to have been under selection. The myostatin gene (GDF-8) has been shown to be associated with double muscling, a phenotype selected for in a number of cattle breeds. We examined population genetic parameters for microsatellite loci at varying distances from GDF-8 in double-muscled (DM) and non-double-muscled (non-DM) cattle breeds in order to assess patterns of diversity. A theoretical analysis was also performed to predict the patterns of diversity expected under different scenarios. We found differences in the patterns of heterozygosity, allele diversity and linkage disequilibrium between DM and non-DM breeds. However, there were some exceptions to the predicted patterns. These are discussed in light of the histories of the breeds and the potential for using microsatellite diversity for mapping trait genes in livestock populations.     

Haplotype diversity in the equine myostatin gene with focus on variants associated with race distance propensity and muscle fiber type proportions

Two variants in the equine myostatin gene (MSTN), including a T/C SNP in the first intron and a 227‐bp SINE insertion in the promoter, are associated with muscle fiber type proportions in the Quarter Horse (QH) and with the prediction of race distance propensity in the Thoroughbred (TB). Genotypes from these loci, along with 18 additional variants surrounding MSTN, were examined in 301 horses of 14 breeds to evaluate haplotype relationships and diversity. The C allele of intron 1 was found in 12 of 14 breeds at a frequency of 0.27; the SINE was observed in five breeds, but common in only the TB and QH (0.73 and 0.48 respectively). Haplotype data suggest the SINE insertion is contemporary to and arose upon a haplotype containing the intron 1 C allele. Gluteal muscle biopsies of TBs showed a significant association of the intron 1 C allele and SINE with a higher proportion of Type 2B and lower proportion of Type 1 fibers. However, in the Belgian horse, in which the SINE is not present, the intron 1 SNP was not associated with fiber type proportions, and evaluation of fiber type proportions across the Belgian, TB and QH breeds shows the significant effect of breed on fiber type proportions is negated when evaluating horses without the SINE variant. These data suggest the SINE, rather than the intron 1 SNP, is driving the observed muscle fiber type characteristics and is the variant targeted by selection for short‐distance racing.     

A genome map of divergent artificial selection between Bos taurus dairy cattle and Bos taurus beef cattle

A number of cattle breeds have become highly specialized for milk or beef production, following strong artificial selection for these traits. In this paper, we compare allele frequencies from 9323 single nucleotide polymorphism (SNP) markers genotyped in dairy and beef cattle breeds averaged in sliding windows across the genome, with the aim of identifying divergently selected regions of the genome between the production types. The value of the method for identifying selection signatures was validated by four sources of evidence. First, differences in allele frequencies between dairy and beef cattle at individual SNPs were correlated with the effects of those SNPs on production traits. Secondly, large differences in allele frequencies generally occurred in the same location for two independent data sets (correlation 0.45) between sliding window averages. Thirdly, the largest differences in sliding window average difference in allele frequencies were found on chromosome 20 in the region of the growth hormone receptor gene, which carries a mutation known to have an effect on milk production traits in a number of dairy populations. Finally, for the chromosome tested, the location of selection signatures between dairy and beef cattle was correlated with the location of selection signatures within dairy cattle.     

Worldwide genetic structure in 37 genes important in telomere biology

Telomeres form the ends of eukaryotic chromosomes and are vital in maintaining genetic integrity. Telomere dysfunction is associated with cancer and several chronic diseases. Patterns of genetic variation across individuals can provide keys to further understanding the evolutionary history of genes. We investigated patterns of differentiation and population structure of 37 telomere maintenance genes among 53 worldwide populations. Data from 898 unrelated individuals were obtained from the genome-wide scan of the Human Genome Diversity Panel (HGDP) and from 270 unrelated individuals from the International HapMap Project at 716 single-nucleotide polymorphism (SNP) loci. We additionally compared this gene set to HGDP data at 1396 SNPs in 174 innate immunity genes. The majority of the telomere biology genes had low to moderate haplotype diversity (45-85%), high ancestral allele frequencies (>60%) and low differentiation (FST<0.10). Heterozygosity and differentiation were significantly lower in telomere biology genes compared with the innate immunity genes. There was evidence of evolutionary selection in ACD, TERF2IP, NOLA2, POT1 and TNKS in this data set, which was consistent in HapMap 3. TERT had higher than expected levels of haplotype diversity, likely attributable to a lack of linkage disequilibrium, and a potential cancer-associated SNP in this gene, rs2736100, varied substantially in genotype frequency across major continental regions. It is possible that the genes under selection could influence telomere biology diseases. As a group, there appears to be less diversity and differentiation in telomere biology genes than in genes with different functions, possibly due to their critical role in telomere maintenance and chromosomal stability.     

Introgression and the fate of domesticated genes in a wild mammal population

When domesticated species are not reproductively isolated from their wild relatives, the opportunity arises for artificially selected variants to be re‐introduced into the wild. However, the evolutionary consequences of introgression of domesticated genes back into the wild are poorly understood. By combining high‐throughput genotyping with 25 years of long‐term ecological field data, we describe the occurrence and consequences of admixture between a primitive sheep breed, the free‐living Soay sheep of St Kilda, and more modern breeds. Utilizing data from a 50 K ovine SNP chip, together with forward simulations of demographic scenarios, we show that admixture occurred between Soay sheep and a more modern breed, consistent with historical accounts, approximately 150 years ago. Haplotype‐sharing analyses with other breeds revealed that polymorphisms in coat colour and pattern in Soay sheep arose as a result of introgression of genetic variants favoured by artificial selection. Because the haplotypes carrying the causative mutations are known to be under natural selection in free‐living Soay sheep, the admixture event created an opportunity to observe the outcome of a ‘natural laboratory’ experiment where ancestral and domesticated genes competed with each other. The haplotype carrying the domesticated light coat colour allele was favoured by natural selection, while the haplotype associated with the domesticated self coat pattern allele was associated with decreased survival. Therefore, we demonstrate that introgression of domesticated alleles into wild populations can provide a novel source of variation capable of generating rapid evolutionary changes.     

Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

ABSTRACT: BACKGROUND: MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds. RESULTS: A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima'D, and Fu and Li's D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. CONCLUSIONS: Chinese and Western breeds have similar nucleotide diversity but evolve divergently in the MUC4 region. Western breeds exhibited unusual low LD extent at the MUC4 locus, reflecting the complexity of nucleotide variability of pig genome. The finding suggests that high density (e.g. 1SNP/10 kb) markers are required to capture the underlying causal variants at such regions.     

Genome‐wide single‐generation signatures of local selection in the panmictic European eel

Next‐generation sequencing and the collection of genome‐wide data allow identifying adaptive variation and footprints of directional selection. Using a large SNP data set from 259 RAD‐sequenced European eel individuals (glass eels) from eight locations between 34 and 64^oN, we examined the patterns of genome‐wide genetic diversity across locations. We tested for local selection by searching for increased population differentiation using F_ST‐based outlier tests and by testing for significant associations between allele frequencies and environmental variables. The overall low genetic differentiation found (F_ST = 0.0007) indicates that most of the genome is homogenized by gene flow, providing further evidence for genomic panmixia in the European eel. The lack of genetic substructuring was consistent at both nuclear and mitochondrial SNPs. Using an extensive number of diagnostic SNPs, results showed a low occurrence of hybrids between European and American eel, mainly limited to Iceland (5.9%), although individuals with signatures of introgression several generations back in time were found in mainland Europe. Despite panmixia, a small set of SNPs showed high genetic differentiation consistent with single‐generation signatures of spatially varying selection acting on glass eels. After screening 50 354 SNPs, a total of 754 potentially locally selected SNPs were identified. Candidate genes for local selection constituted a wide array of functions, including calcium signalling, neuroactive ligand–receptor interaction and circadian rhythm. Remarkably, one of the candidate genes identified is PERIOD, possibly related to differences in local photoperiod associated with the >30° difference in latitude between locations. Genes under selection were spread across the genome, and there were no large regions of increased differentiation as expected when selection occurs within just a single generation due to panmixia. This supports the conclusion that most of the genome is homogenized by gene flow that removes any effects of diversifying selection from each new generation.     

Genetic Structuring of Nine Indian Domestic Goat Breeds Based on SNPs Identified in IGF-1 Gene

The caprine Insulin like Growth Factor1 (IGF1) gene was analyzed for identification of single nucleotide polymorphisms (SNPs) and genetic structuring of Indian goat breeds. A panel of 80 samples belonging to nine Indian goat breeds (Capra hircus) including three large sized breeds (Jamunapari, Beetal and Jakhrana); three medium sized breeds (Sirohi, Barbari, and Osmanabadi) and three small sized breeds (Black Bengal, Changthangi, and Gaddi) were screened for SNP identification and diversity analysis. The comparative gene sequence analysis of all the nine goat breeds studied revealed a total of 18 SNPs in IGF1 gene. All the nucleotide changes were found to be synonymous. The mean observed heterozygosity was found to be maximum (0.074) in Sirohi, Beetal, Osmanabadi, and Gaddi breeds of goat, whereas it is found to be minimum (0.019) in Black Bengal breed of goat. The rest of the breeds were intermediate in terms of heterozygosity. The same has been confirmed by allele frequency distribution across the studied loci. Barbari and Gaddi were found to be more differentiated (0.0123), Changthangi and Jamunapari were least differentiated (0.00110) based on Nei's genetic distance.     

鸡瘦蛋白受体(OBR)基因外显子9单核苷酸多态性分析

瘦蛋白受体属于Ⅰ类细胞因子超家族受体,其在瘦蛋白的信号转导中起着关键的作用。本研究根据瘦蛋白受体基因外显子9的序列设计引物,用PCR-SSCP的方法对高脂系（fatness line,FL）、低脂系(leanness line,LL)、北京油鸡、白耳鸡、石歧杂、矮小黄鸡、小型黄鸡、惠阳胡须鸡、隐性白羽鸡和海兰蛋鸡等品种（系）进行了单核苷酸多态性分析,并检测到了多态性。对两种纯合子片段克隆和测序,结果表明在编码区的1167位碱基发生了突变,由C突变为A,但是编码的氨基酸并没有发生改变。经独立性检验,基因型频率和基因频率分布与品种有关,北京油鸡的AA基因型频率显著高于其他品种;高脂系中A基因频率显著高于低脂系。 Abstract:Leptin receptor is a type I cytokine super family member and plays an important role in leptin functioning signal transduction.This study was designed to investigate the single nucleotide polymorphism (SNP) of OBR gene in various breeds,including Fatness Line (FL),Leanness Line (LL),Beijing Youji,Baierji,Shiqiza,Dwarf Yellow Chickens,Mini Yellow Chickens,Huiyang Huxuji,Recessive White Chickens and Hyline Layer.The primers for exon 9 in OBR gene were designed from the database of chicken genomic sequence and the SNPs were detected by PCR-SSCP method.One SNP (C/A at 1167 in cds) was found among individuals within all breeds.However,the amino acid was not changed because it was a silence mutantion.The result of population genetics analyses showed that the frequency of AA genotype in Beijing Youji was significantly higher than that in other lines.Also,the frequency of A allele in FL was significantly higher than that in LL.     

Single-strand conformational polymorphism and sequence polymorphism of Mhc-DRB in Latxa and Karrantzar sheep: implications for Caprinae phylogeny

Single-strand conformational polymorphism analysis and DNA sequencing were used to characterize Mhc-DRB second exon variability in the Latxa and Karrantzar breeds of sheep. The presence of more than two sequences in some animals indicates that alleles of two different loci have been amplified. Six new alleles were identified by sequencing. The allele frequency distribution of the DRB1 gene is striking, with two alleles accounting for half of the gene pool in both breeds under study. The most frequent allele in both breeds was the same (named DRB1*0702), with some specific amino acids: Tyr in position 31 and Thr in 51. A species variability analysis was also performed including the entire set of sheep DRB exon 2 sequences. Based on the patchwork patterns of different alleles, interallelic recombination appears to be playing a significant role in the generation of allelic diversity at this locus in sheep. The phylogenetic tree of all known Caprinae DRB sequences shows that certain alleles from one species are more closely related to those from other species than they are to each other. Allele DRB1*0702 merits special attention due to its high similarity to the Mufflon allele. As this is the most frequent in both breeds analyzed, one can hypothesize that in sheep, both Mufflon and Argali have had different influences depending on the sheep breed under study and that the relationship between domestic sheep and Mufflon is greater than previously thought. The data generated in this study can serve as a basis for developing a typing assay for the sheep DRB genes in the Latxa and Karrantzar populations.     

Adaptive molecular evolution of MC1R gene reveals the evidence for positive diversifying selection in indigenous goat populations

Detecting signatures of selection can provide a new insight into the mechanism of contemporary breeding and artificial selection and further reveal the causal genes associated to the phenotypic variation. However, the signatures of selection on genes entailing for profitable traits between Chinese commercial and indigenous goats have been poorly interpreted. We noticed footprints of positive selection at MC 1R gene containing SNP s genotyped in five Chinese native goat breeds. An experimental distribution of F _ST was built based on approximations of F _ST for each SNP across five breeds. We identified selection using the high F _ST outlier method and found that MC 1R candidate gene show evidence of positive selection. Furthermore, adaptive selection pressure on specific codons was determined using different codon based on maximum‐likelihood methods; signature of positive selection in mammalian MC 1R was explored in individual codons. Evolutionary analyses were inferred under maximum likelihood models, the HyPhy package implemented in the DATAMONKEY Web Server. The results of codon selection displayed positive diversifying selection at the sites were mainly involved in development of genetic variations in coat color in various mammalian species. Positive diversifying selection inferred with recent evolutionary changes in domesticated goat MC 1R provides new insights that the gene evolution may have been modulated by domestication events in goats.     

Selection at linked sites in the partial selfer Caenorhabditis elegans

Natural selection can produce a correlation between local recombination rates and levels of neutral DNA polymorphism as a consequence of genetic hitchhiking and background selection. Theory suggests that selection at linked sites should affect patterns of neutral variation in partially selfing populations more dramatically than in outcrossing populations. However, empirical investigations of selection at linked sites have focused primarily on outcrossing species. To assess the potential role of selection as a determinant of neutral polymorphism in the context of partial self-fertilization, we conducted a multivariate analysis of single-nucleotide polymorphism (SNP) density throughout the genome of the nematode Caenorhabditis elegans. We based the analysis on a published SNP data set and partitioned the genome into windows to calculate SNP densities, recombination rates, and gene densities across all six chromosomes. Our analyses identify a strong, positive correlation between recombination rate and neutral polymorphism (as estimated by noncoding SNP density) across the genome of C. elegans. Furthermore, we find that levels of neutral polymorphism are lower in gene-dense regions than in gene-poor regions in some analyses. Analyses incorporating local estimates of divergence between C. elegans and C. briggsae indicate that a mutational explanation alone is unlikely to explain the observed patterns. Consequently, we interpret these findings as evidence that natural selection shapes genome-wide patterns of neutral polymorphism in C. elegans. Our study provides the first demonstration of such an effect in a partially selfing animal. Explicit models of genetic hitchhiking and background selection can each adequately describe the relationship between recombination rate and SNP density, but only when they incorporate selfing rate. Clarification of the relative roles of genetic hitchhiking and background selection in C. elegans awaits the development of specific theoretical predictions that account for partial self-fertilization and biased sex ratios.     

Sexual Antagonism,Temporally Fluctuating Selection,and Variable Dominance Affect a Regulatory Polymorphism in Drosophila melanogaster

Understanding how genetic variation is maintained within species is a major goal of evolutionary genetics that can shed light on the preservation of biodiversity. Here, we examined the maintenance of a regulatory single-nucleotide polymorphism (SNP) of the X-linked Drosophila melanogaster gene fezzik. The derived variant at this site is at intermediate frequency in many worldwide populations but absent in populations from the ancestral species range in sub-Saharan Africa. We collected and genotyped wild-caught individuals from a single European population biannually over a period of 5 years, which revealed an overall difference in allele frequency between the sexes and a consistent change in allele frequency across seasons in females but not in males. Modeling based on the observed allele and genotype frequencies suggested that both sexually antagonistic and temporally fluctuating selection may help maintain variation at this site. The derived variant is predicted to be female-beneficial and mostly recessive; however, there was uncertainty surrounding our dominance estimates and long-term modeling projections suggest that it is more likely to be dominant. By examining gene expression phenotypes, we found that phenotypic dominance was variable and dependent upon developmental stage and genetic background, suggesting that dominance may be variable at this locus. We further determined that fezzik expression and genotype are associated with starvation resistance in a sex-dependent manner, suggesting a potential phenotypic target of selection. By characterizing the mechanisms of selection acting on this SNP, our results improve our understanding of how selection maintains genetic and phenotypic variation in natural populations.     

Mapping and genotypic analysis of the NK-lysin gene in chicken

Background

Antimicrobial peptides (AMP) are important elements of the first line of defence against pathogens in animals. NK-lysin is a cationic AMP that plays a critical role in innate immunity. The chicken NK-lysin gene has been cloned and its antimicrobial and anticancer activity has been described but its location in the chicken genome remains unknown. Here, we mapped the NK-lysin gene and examined the distribution of a functionally significant single nucleotide polymorphism (SNP) among different chicken inbred lines and heritage breeds.

Results

A 6000 rad radiation hybrid panel (ChickRH6) was used to map the NK-lysin gene to the distal end of chromosome 22. Two additional genes, the adipocyte enhancer-binding protein 1-like gene (AEBP1) and the DNA polymerase delta subunit 2-like (POLD2) gene, are located in the same {"type":"entrez-nucleotide","attrs":{"text":"NW_003779909","term_id":"358468969","term_text":"NW_003779909"}}NW_003779909 contig as NK-lysin, and were thus indirectly mapped to chromosome 22 as well. Previously, we reported a functionally significant SNP at position 271 of the NK-lysin coding sequence in two different chicken breeds. Here, we examined this SNP and found that the A allele appears to be more common than the G allele in these heritage breeds and inbred lines.

Conclusions

The chicken NK-lysin gene mapped to the distal end of chromosome 22. Two additional genes, AEBP1 and POLD2, were indirectly mapped to chromosome 22 also. SNP analyses revealed that the A allele, which encodes a peptide with a higher antimicrobial activity, is more common than the G allele in our tested inbred lines and heritage breeds.     

Signatures of adaptation and genetic structure among the mainland populations of Pinus radiata (D. Don) inferred from SNP loci

Insights into the relative contributions of locus specific and genome-wide effects on population genetic diversity can be gained through separation of their resulting genetic signals. Here we explore patterns of adaptive and neutral genetic diversity in the disjunct natural populations of Pinus radiata (D. Don) from mainland California. A first-generation common garden of 447 individuals revealed significant differentiation of wood phenotypes among populations (P _ST), possibly reflecting local adaptation in response to environment. We subsequently screened all trees for genetic diversity at 149 candidate gene single nucleotide polymorphism (SNP) loci for signatures of adaptation. Ten loci were identified as being possible targets of diversifying selection following F _ST outlier tests. Multivariate canonical correlation performed on a data set of 444 individuals identified significant covariance between environment, adaptive phenotypes and outlier SNP diversity, lending support to the case for local adaptation suggested from F _ST and P _ST tests. Covariation among discrete sets of outlier SNPs and adaptive phenotypes (inferred from multivariate loadings) with environment are supported by existing studies of candidate gene function and genotype–phenotype association. Canonical analyses failed to detect significant correlations between environment and 139 non-outlier SNP loci, which were applied to estimate neutral patterns of genetic differentiation among populations (F _ST 4.3 %). Using this data set, significant hierarchical structure was detected, indicating three populations on the mainland. The hierarchical relationships based on neutral SNP markers (and SSR) were in contrast with those inferred from putatively adaptive loci, potentially highlighting the independent action of selection and demography in shaping genetic structure in this species.     

An effect of a missense mutation in the porcine melanocortin-4 receptor (MC4R) gene on production traits in Polish pig breeds is doubtful

A missense G-A SNP in the porcine melanocortin-4 receptor (MC4R) gene that causes an Asp-Asn substitution at position 298 of the corresponding MC4R protein is considered to be economically important, although published results on its effect are inconsistent. We analysed the association of this MC4R polymorphism with production traits in 679 gilts from two breeds, Polish Large White (PLW) and Polish Landrace (PL), as well as one synthetic line 990. The frequency of the A allele differed significantly among the breeds with frequencies of 0.76, 0.29 and 0.16 in PLW, PL and line 990 respectively. There was no evidence of an effect of this polymorphism on daily food intake, backfat thickness or abdominal fat. The A allele was correlated with higher test daily gains and lower levels of intramuscular fat in PL, and increased levels of intramuscular fat in PLW.