Variation In Allele Frequencies Research Articles

Opportunities and challenges in assessing climate change vulnerability through genomics

By investigating how past selection has affected allele frequencies across space, genomic tools are providing new insights into adaptive evolutionary processes. Now researchers are considering how this genomic information can be used to predict the future vulnerability of species under climate change. Genomic vulnerability assessments show promise, but challenges remain.

A comparative analysis of SLA-DRB1 genetic diversity in Colombian (creoles and commercial line) and worldwide swine populations

Analysing pig class II mayor histocompatibility complex (MHC) molecules is mainly related to antigen presentation. Identifying frequently-occurring alleles in pig populations is an important aspect to be considered when developing peptide-based vaccines. Colombian creole pig populations have had to adapt to local conditions since entering Colombia; a recent census has shown low amounts of pigs which is why they are considered protected by the Colombian government. Commercial hybrids are more attractive regarding production. This research has been aimed at describing the allele distribution of Colombian pigs from diverse genetic backgrounds and comparing Colombian SLA-DRB1 locus diversity to that of internationally reported populations. Twenty SLA-DRB1 alleles were identified in the six populations analysed here using sequence-based typing. The amount of alleles ranged from six (Manta and Casco Mula) to nine (San Pedreño). Only one allele (01:02) having > 5% frequency was shared by all three commercial line populations. Allele 02:01:01 was shared by five populations (around > 5% frequency). Global FST indicated that pig populations were clearly structured, as 20.6% of total allele frequency variation was explained by differences between populations (FST = 0.206). This study’s results confirmed that the greatest diversity occurred in wild boars, thereby contrasting with low diversity in domestic pig populations.

Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease

SummaryWhether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Global adaptation complicates the interpretation of genome scans for local adaptation.

Spatially varying selection promotes variance in allele frequencies, increasing genetic differentiation between the demes of a metapopulation. For that reason, outliers in the genome‐wide distribution of summary statistics measuring genetic differentiation, such as FST, are often interpreted as evidence for alleles that contribute to local adaptation. However, theoretical studies have shown that in spatially structured populations the spread of beneficial mutations with spatially uniform fitness effects can also induce transient genetic differentiation. In recent years, numerous empirical studies have suggested that such species‐wide, or global, adaptation makes a substantial contribution to molecular evolution. In this perspective, we discuss how commonly such global adaptation may influence the genome‐wide distribution of FST and generate genetic differentiation patterns, which could be mistaken for local adaptation. To illustrate this, we use forward‐in‐time population genetic simulations assuming parameters for the rate and strength of beneficial mutations consistent with estimates from natural populations. We demonstrate that the spread of globally beneficial mutations in parapatric populations may frequently generate FST outliers, which could be misinterpreted as evidence for local adaptation. The spread of beneficial mutations causes selective sweeps at flanking sites, so in some cases, the effects of global versus local adaptation may be distinguished by examining patterns of nucleotide diversity within and between populations in addition to FST. However, when local adaptation has been only recently established, it may be much more difficult to distinguish from global adaptation, due to less accumulation of linkage disequilibrium at flanking sites. Through our discussion, we conclude that a large fraction of FST outliers that are presumed to arise from local adaptation may instead be due to global adaptation.

Genetic diversity and restricted genetic connectivity in an endangered marine fish (

Determining the genetic diversity and differentiation among populations is a critical element of conservation biology, but for many aquatic, data-deficient species with small population sizes, this is not possible. Closely related species may therefore provide a model. For the first time, using over 4000 single-nucleotide polymorphism loci, we characterise the population genetic diversity and structure of one of the world’s rarest marine fish, the spotted handfish (Brachionichthys hirsutus), a species which is also a member of the most threatened marine bony fish family (Brachionichthyidae). Fin clips were taken from 170 live spotted handfish across seven disjunct sites within the only known estuary (in Tasmania, Australia) where multiple populations of the species are found. Spatially discrete populations clustered into three genetic groupings and a significant variance in allele frequencies among populations (overall FST = 0.043), even at the small scale of the estuary, was observed. Furthermore, low contemporary migration rate estimates suggest low genetic homogeneity between locations. Because of the low genetic connectivity, population clusters of spotted handfish within the estuary should be considered as separate conservation management units. This insight should be considered for management and conservation strategies of other data-deficient and threatened species in the family.

Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome P450 2C19 gene in six major ethnicities of Pakistan

ABSTRACT Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.

High genetic drift in endangered northern peripheral populations of the Behr's hairstreak butterfly (Satyrium behrii)

Abstract The persistence and adaptation of leading‐edge peripheral populations may be critical for allowing species to shift their range limits under climate change. However, peripheral populations are potentially vulnerable to genetic, demographic, and environmental stochasticity. Here, we characterise genetic variation across space and among years in northern peripheral populations of the Behr's hairstreak butterfly in British Columbia, Canada. This butterfly is dependent on antelope‐brush ecosystems that are threatened in this part of the world and is federally listed as Endangered in Canada. Using a large panel of amplified fragment length polymorphism (AFLP) genetic markers, we found low diversity in these populations. We also detected a high degree of year‐to‐year variation in allele frequencies, resulting in low effective population size estimates. Our findings suggest that Canadian populations of the Behr's hairstreak experience high genetic drift and may be vulnerable to genetic stochasticity. Unstable demography, low effective population size, and low genetic diversity in these populations could impede their adaptation to rapidly changing environmental conditions and contribute to a contraction of the species' range under climate change.

A variant-centric perspective on geographic patterns of human allele frequency variation.

A key challenge in human genetics is to understand the geographic distribution of human genetic variation. Often genetic variation is described by showing relationships among populations or individuals, drawing inferences over many variants. Here, we introduce an alternative representation of genetic variation that reveals the relative abundance of different allele frequency patterns. This approach allows viewers to easily see several features of human genetic structure: (1) most variants are rare and geographically localized, (2) variants that are common in a single geographic region are more likely to be shared across the globe than to be private to that region, and (3) where two individuals differ, it is most often due to variants that are found globally, regardless of whether the individuals are from the same region or different regions. Our variant-centric visualization clarifies the geographic patterns of human variation and can help address misconceptions about genetic differentiation among populations.

Polymorphism of lncRNAs in breast cancer: Meta-analysis shows no association with susceptibility.

Long non-coding RNAs (lncRNAs) have been the target of considerable attention for their roles in many biological processes. Only a small portion of lncRNAs are functionally characterized, and several approaches have been proposed for investigating the roles of these molecules, including how polymorphisms in lncRNA genomic sites may interfere with their function. Allele frequency variation in single nucleotide polymorphisms (SNPs), for example, has been associated with several diseases, including breast cancer (BC), the most common type of cancer in women. In the present study, we performed a systematic review of lncRNA SNPs associated with BC and a meta-analysis of some lncRNA SNPs. We found 31 SNPs mapped in 12 lncRNAs associated with BC in 28 case-control studies. Our meta-analysis showed an insignificant difference between the SNPs rs217727, rs3741219, rs2107425 and rs2839698 on H19, as well as rs920778, rs1899663, rs12826786 and rs4759314 on HOTAIR, and BC susceptibility. The present analysis recognized the importance of extensive association studies, including different populations, and further evaluation of potential functional effects caused by lncRNA SNPs. Nevertheless, genetic variants such as SNPs in lncRNAs may play many other essential roles, although this field is still under explored.

Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.

Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV1 ], forced vital capacity [FVC], and FEV1 /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3.

Balancing selection versus allele and supertype turnover in MHC class II genes in guppies.

Selection pressure from parasites is thought to be a major force shaping the extreme polymorphism of the major histocompatibility complex (MHC) genes, but the modes and consequences of selection remain unclear. Here, we analyse MHC class II and microsatellite diversity in 16 guppy (Poecilia reticulata) populations from two islands (Trinidad and Tobago) that have been separated for at least 10 ky. Within-population MHC diversity was high, but allele sharing was limited within islands and even lower between islands, suggesting relatively fast turnover of alleles. Allelic lineages strongly supported in phylogenetic analyses tended to be island-specific, suggesting rapid lineage sorting, and an expansion of an allelic lineage private to Tobago was observed. New alleles appear to be generated locally at a detectably high frequency. We did not detect a consistent signature of local adaptation, but FST outlier analysis suggested that balancing selection may be the more general process behind spatial variation in MHC allele frequencies in this system, particularly within Trinidad. We found no evidence for divergent allele advantage within populations, or for decreased genetic structuring of MHC supertypes compared to MHC alleles. The dynamic and complex nature of MHC evolution we observed in guppies, coupled with some evidence for balancing selection shaping MHC allele frequencies, are consistent with Red Queen processes of host-parasite coevolution.

Genetic divergence of selected and wild populations of Pacific oysters (Crassostrea gigas) on the West Coast of North America

The Molluscan Broodstock Program (MBP) has been selecting Pacific oysters Crassostrea gigas for improved yield for over two decades. Nevertheless, realized gain in yield, the percent difference in least-square mean yield between MBP and pooled control families made from “wild” stock, was reported to be zero in the fifth generation. Among the potential explanations for zero realized gain was that MBP-derived stock had spread or reproduced in bays with extensive oyster farming and contributed to the “wild” broodstock used for the control population. This “MBP = wild” hypothesis was tested by analyses of genetic data from four MBP cohorts and 11 wild populations, including founders of MBP cohorts. A new 2016 sample from Willapa Bay, the primary source of MBP's control families, was genotyped by high-resolution melting (HRM) of 45, SNP-containing PCR amplicons and compared to previous HRM data for a 1996 sample. Average temporal variance in allele frequencies for Willapa Bay implies a small, local, effective population size (Ne = 55, 95% CI, 32–159) with very high gene flow among Pacific Northwest populations (migration rate, m = 0.99, 95% CI, 0.25–1.0). These estimates, which are remarkably consistent with previous estimates, also based on 20-y intervals, for populations in Pipestem Inlet and Dabob Bay, support the general conclusion that the North American Pacific oyster metapopulation is evolving by genetic drift, likely owing to local sweepstakes reproductive processes, with high gene flow maintaining spatial similarity. Direct comparison of MBP and wild populations reveals 7× more genetic divergence between selected and wild populations than among wild populations. Evidence for genetic drift within the Willapa Bay wild population that is uncorrelated with genetic drift in Dabob Bay, together with evidence for genetic drift between MBP and all wild populations studied to date, falsifies the hypothesis that gene flow from MBP-derived commercial stocks to wild populations is responsible for a realized gain in yield of zero. Further analyses of parentage and relatedness in four MBP cohorts suggests that pedigree errors may have contributed to inaccuracies in the selective breeding program and resulted in the observed realized gain in yield of zero.

Abstract B064: Race-related genetic variation and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer

Abstract Prostate cancer (PCa) is the most prevalent cancer and third leading cause of cancer death among men in the United States. PCa incidence, aggressiveness and mortality are significantly higher among African Americans (AAs) compared with men of other racial groups. Despite the worse prognosis associated with African ancestry, several recent studies have shown that PCa patients of African ancestry have a better response to certain PCa therapeutic regimens than those of European ancestry. The overall objective of our study is to identify ancestry-related genetic variation that associates with outcomes on abiraterone/prednisone therapy in metastatic castration-resistant prostate cancer (mCRPC). Our central hypothesis is that differences in ancestry-related single nucleotide polymorphisms (SNPs), gene expression and/or metabolites will associate with prostate-specific antigen (PSA) response and time to progression on secondary hormonal therapy in mCRPC patients. Toward our objective, we collected whole blood, archival tumor tissue and serum from 50 self-identified AA and 50 self-identified white patients enrolled in the Abi Race study, a Phase II study of abiraterone/prednisone in AA and white men with mCRPC. To perform ancestral and genome-wide genotyping, we isolated DNA from the whole blood samples collected at baseline and interrogated DNA using the Infinium Multi-Ethnic Global BeadChip (Illumina). Preliminary analysis identified 622 SNPs that associated with PSA progression-free survival on abiraterone or variation in minor allele frequency by ancestry. To perform gene expression profiling, we isolated RNA from archival formalin-fixed, paraffin-embedded PCa tissue and interrogated RNA using a NanoString Custom CodeSet (NanoString Technologies). Preliminary analysis revealed significant race-related differential expression of 30 prostate cancer-related genes. To perform metabolomic profiling, we used fasting serum samples collected at baseline and during treatment and the Biocrates p400 HR Kit (Biocrates Life Sciences AG). From this analysis, we have prioritized four ancestry-related metabolites associated with time to confirmed PSA progression for further study. Future analyses will focus on defining the functional significance of the aforementioned ancestry-related genetic variation using preclinical cancer models and validation of the aforementioned ancestry-related genetic variation in an independent cohort. These findings will further understanding of ancestry-related biological factors that influence response to secondary hormonal therapy in mCRPC and could have direct implications for the timing and selection of AA patients for secondary hormonal therapy and those needing additional therapy. As secondary hormonal therapy use expands to earlier disease settings, these findings could support the need for further studies in AA men in these disease settings. Ultimately, such strategies have the potential to mitigate PCa disparity. Citation Format: Tyler A Allen, Gary Lipton, Alexander B Sibley, Patrick Healy, Brendon M Patierno, Bonnie Lacroix, Steven R Patierno, Kouros Owzar, Terry Hyslop, Daniel J George, Jennifer A Freedman. Race-related genetic variation and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B064.

Selection signatures in tropical cattle are enriched for promoter and coding regions and reveal missense mutations in the damage response gene HELB

BackgroundDistinct domestication events, adaptation to different climatic zones, and divergent selection in productive traits have shaped the genomic differences between taurine and indicine cattle. In this study, we assessed the impact of artificial selection and environmental adaptation by comparing whole-genome sequences from European taurine and Asian indicine breeds and from African cattle. Next, we studied the impact of divergent selection by exploiting predicted and experimental functional annotation of the bovine genome.ResultsWe identified selective sweeps in beef cattle taurine and indicine populations, including a 430-kb selective sweep on indicine cattle chromosome 5 that is located between 47,670,001 and 48,100,000 bp and spans five genes, i.e. HELB, IRAK3, ENSBTAG00000026993, GRIP1 and part of HMGA2. Regions under selection in indicine cattle display significant enrichment for promoters and coding genes. At the nucleotide level, sites that show a strong divergence in allele frequency between European taurine and Asian indicine are enriched for the same functional categories. We identified nine single nucleotide polymorphisms (SNPs) in coding regions that are fixed for different alleles between subspecies, eight of which were located within the DNA helicase B (HELB) gene. By mining information from the 1000 Bull Genomes Project, we found that HELB carries mutations that are specific to indicine cattle but also found in taurine cattle, which are known to have been subject to indicine introgression from breeds, such as N’Dama, Anatolian Red, Marchigiana, Chianina, and Piedmontese. Based on in-house genome sequences, we proved that mutations in HELB segregate independently of the copy number variation HMGA2-CNV, which is located in the same region.ConclusionsMajor genomic sequence differences between Bos taurus and Bos indicus are enriched for promoter and coding regions. We identified a 430-kb selective sweep in Asian indicine cattle located on chromosome 5, which carries SNPs that are fixed in indicine populations and located in the coding sequences of the HELB gene. HELB is involved in the response to DNA damage including exposure to ultra-violet light and is associated with reproductive traits and yearling weight in tropical cattle. Thus, HELB likely contributed to the adaptation of tropical cattle to their harsh environment.

Monitoring of PIK3CA and ESR1 mutations in circulating tumor DNA as predictive and prognostic biomarkers in patients with endocrine-resistant ER+/HER2- advanced breast cancer.

e13045 Background: Combination therapeutic strategies including CDK4/6 inhibitors and an endocrine backbone are the standard of care of treatment for patients with estrogen receptor positive (ER+)/HER2- advanced breast cancer (ABC). Endocrine agents mainly include aromatase inhibitors, which target ER-driven transcription, and fulvestrant, which functions as ER antagonist. PI3K-AKT-mTOR is a key point of resistance to endocrine therapy, activated in 40% of these patients by mutations concentrated in critical regions of PIK3CA, coding for the p110 catalytic subunit α of PI3K. Additionally, 30% of patients previously exposed to non-steroidal aromatase inhibitors develop mutations in the ligand binding domain of ESR1, causing endocrine resistance by constitutive activation of the ER. Furthermore, metastasis and primary tumors may show a highly heterogenous mutational landscape. Monitoring the dynamic changes of these mutations in ctDNA may provide a non-invasive, real-time and accessible tool to convey predictive/prognostic information and guide decisions on sequential endocrine therapies. Methods: Pre-planned interim analysis results of an observational, prospective cohort pilot study to assess the predictive and prognostic value of monitoring PIK3CA and ESR1 mutations in ctDNA of patients with endocrine-resistant ER+/HER2- ABC. We have studied longitudinal liquid biopsies from 30 patients using digital PCR to interrogate PIK3CA mutations (H1047R / E545K) and ESR1 mutations (D538G / Y537S). Blood samples were drawn at the time of progression to endocrine therapy, at 8 weeks of subsequent endocrine line and at new progression. This exploratory analysis will provide preliminary data on clinical homogeneity, treatment regimens, median follow-up and progression-free survival, mutation incidence and intraindividual variation of mutant allele frequency and copy number. The percentage of progressors at 24 weeks of follow-up according to the mutational status will be evaluated by using the Fisher’s exact test. The predictive potential of ctDNA biomarkers will be characterized by ROC curve analysis. Tracking ctDNA mutations to predict endocrine resistance in a real-world setting represents a critical step towards precision medicine in oncology.

Quantitative evaluation of the molecular marker using droplet digital PCR.

Transposable elements (TEs) constitute approximately half of Bovine genome. They can be a powerful species-specific marker without regression mutations by the structure variation (SV) at the time of genomic evolution. In a previous study, we identified the Hanwoo-specific SV that was generated by a TE–association deletion event using traditional PCR method and Sanger sequencing validation. It could be used as a molecular marker to distinguish different cattle breeds (i.e., Hanwoo vs. Holstein). However, PCR is defective with various final copy quantifications from every sample. Thus, we applied to the droplet digital PCR (ddPCR) platform for accurate quantitative detection of the Hanwoo-specific SV. Although samples have low allele frequency variation within Hanwoo population, ddPCR could perform high sensitive detection with absolute quantification. We aimed to use ddPCR for more accurate quantification than PCR. We suggest that the ddPCR platform is applicable for the quantitative evaluation of molecular markers.

Antimicrobial peptide and sequence variation along a latitudinal gradient in two anurans

BackgroundWhile there is evidence of both purifying and balancing selection in immune defense genes, large-scale genetic diversity in antimicrobial peptides (AMPs), an important part of the innate immune system released from dermal glands in the skin, has remained uninvestigated. Here we describe genetic diversity at three AMP loci (Temporin, Brevinin and Palustrin) in two ranid frogs (Rana arvalis and R. temporaria) along a 2000 km latitudinal gradient. We amplified and sequenced part of the Acidic Propiece domain and the hypervariable Mature Peptide domain (~ 150-200 bp) in the three genes using Illumina Miseq and expected to find decreased AMP genetic variation towards the northern distribution limit of the species similarly to studies on MHC genetic patterns.ResultsWe found multiple loci for each AMP and relatively high gene diversity, but no clear pattern of geographic genetic structure along the latitudinal gradient. We found evidence of trans-specific polymorphism in the two species, indicating a common evolutionary origin of the alleles. Temporin and Brevinin did not form monophyletic clades suggesting that they belong to the same gene family. By implementing codon evolution models we found evidence of strong positive selection acting on the Mature Peptide. We also found evidence of diversifying selection as indicated by divergent allele frequencies among populations and high Theta k values.ConclusionOur results suggest that AMPs are an important source of adaptive diversity, minimizing the chance of microorganisms developing resistance to individual peptides.

Porcine LIF gene polymorphisms and their association with litter size traits in four pig breeds

Leukemia inhibitory factor (LIF) is an important productivity-related gene in pigs. We found two polymorphisms — g.6646C>T and g.6988C>T — in exon 3 of LIF in pigs by using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism. Three genotypes were obtained and associated with litter size traits in Anqing Six-end-white (AQ), Wei (W), Wannan Black (WNB), and Large White (LW) pigs. At locus g.6646C>T, the g.6646C allele frequency variation was 0.6869 (AQ), 0.7473 (W), 1 (WNB), and 0.6852 (LW). In AQ pigs, sows with the TT genotype had higher total number of piglets born (TNB) and number of piglets born alive (NBA) in the first parity and multiparities (P < 0.01). In W and LW pigs, sows with the CC genotype had higher TNB and NBA in multiparities (P < 0.01). At locus g.6988C>T, the g.6988C allele frequency variation was 1 (AQ), 0.6154 (W), 1 (WNB), and 0.6667 (LW). The CC genotype significantly differed from CT or TT genotypes (P < 0.01) for TNB and NBA in W and LW pigs. Thus, LIF was shown to have a significant influence on litter size. Therefore, g.6646C>T and g.6988C>T loci of LIF could be potential marker-assisted selection tools for improving litter size in pig production.

Demographic fluctuations lead to rapid and cyclic shifts in genetic structure among populations of an alpine butterfly, Parnassius smintheus.

Many populations, especially in insects, fluctuate in size, and periods of particularly low population size can have strong effects on genetic variation. Effects of demographic bottlenecks on genetic diversity of single populations are widely documented. Effects of bottlenecks on genetic structure among multiple interconnected populations are less studied, as are genetic changes across multiple cycles of demographic collapse and recovery. We take advantage of a long-term data set comprising demographic, genetic and movement data from a network of populations of the butterfly, Parnassius smintheus, to examine the effects of fluctuating population size on spatial genetic structure. We build on a previous study that documented increased genetic differentiation and loss of spatial genetic patterns (isolation by distance and by intervening forest cover) after a network-wide bottleneck event. Here, we show that genetic differentiation was reduced again and spatial patterns returned to the system extremely rapidly, within three years (i.e. generations). We also show that a second bottleneck had similar effects to the first, increasing differentiation and erasing spatial patterns. Thus, bottlenecks consistently drive random divergence of allele frequencies among populations in this system, but these effects are rapidly countered by gene flow during demographic recovery. Our results reveal a system in which the relative influence of genetic drift and gene flow continually shift as populations fluctuate in size, leading to cyclic changes in genetic structure. Our results also suggest caution in the interpretation of patterns of spatial genetic structure, and its association with landscape variables, when measured at only a single point in time.

Identifying mechanisms of genetic differentiation among populations in vagile species: historical factors dominate genetic differentiation in seabirds.

Elucidating the factors underlying the origin and maintenance of genetic variation among populations is crucial for our understanding of their ecology and evolution, and also to help identify conservation priorities. While intrinsic movement has been hypothesized as the major determinant of population genetic structuring in abundant vagile species, growing evidence indicates that vagility does not always predict genetic differentiation. However, identifying the determinants of genetic structuring can be challenging, and these are largely unknown for most vagile species. Although, in principle, levels of gene flow can be inferred from neutral allele frequency divergence among populations, underlying assumptions may be unrealistic. Moreover, molecular studies have suggested that contemporary gene flow has often not overridden historical influences on population genetic structure, which indicates potential inadequacies of any interpretations that fail to consider the influence of history in shaping that structure. This exhaustive review of the theoretical and empirical literature investigates the determinants of population genetic differentiation using seabirds as a model system for vagile taxa. Seabirds provide a tractable group within which to identify the determinants of genetic differentiation, given their widespread distribution in marine habitats and an abundance of ecological and genetic studies conducted on this group. Herein we evaluate mitochondrial DNA (mtDNA) variation in 73 seabird species. Lack of mutation-drift equilibrium observed in 19% of species coincided with lower estimates of genetic differentiation, suggesting that dynamic demographic histories can often lead to erroneous interpretations of contemporary gene flow, even in vagile species. Presence of land across the species sampling range, or sampling of breeding colonies representing ice-free Pleistocene refuge zones, appear to be associated with genetic differentiation in Tropical and Southern Temperate species, respectively, indicating that long-term barriers and persistence of populations are important for their genetic structuring. Conversely, biotic factors commonly considered to influence population genetic structure, such as spatial segregation during foraging, were inconsistently associated with population genetic differentiation. In light of these results, we recommend that genetic studies should consider potential historical events when identifying determinants of genetic differentiation among populations to avoid overestimating the role of contemporary factors, even for highly vagile taxa.