Footprints Of Selection Research Articles

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.

Genetic heterogeneity and local adaptation of Asian seabass across Indonesian Archipelago revealed with gene-associated SNP markers

Asian seabass is an important marine foodfish species in Asia-Pacific region. Previous studies using microsatellites and mitochondrial DNA sequences showed that the populations in Australia are significantly different from those in Southeast Asia. However, within Australian and Southeast Asian populations, there are some conflicts regarding to population differentiations. It is essential for us to use more DNA markers to examine the population structure of Asian seabass. We collected Asian seabass samples from seven wild populations distributed across Indonesian Archipelago from Southeast Asia to Australia and Papua New Guinea. We measured the genetic diversity within each population and analyzed the genetic relationships among the wild populations using 96 SNPs. We detected significant population differentiations among the seven wild populations of Asian seabass. The genetic diversity in Southeast Asian populations was significantly higher than that in Australian and Papua New Guinean populations. There were significant genetic differentiations among the Australian and Papua New Guinean populations while the differentiation in Southeast Asian populations was minor. In addition, we identified footprints of directional selection at three loci using outlier tests. Our data supply useful information about the management of wild stocks of Asian seabass and the use of wild Asian seabass to start a breeding program.

A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence

Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.

Natural Selection and Functional Potentials of Human Noncoding Elements Revealed by Analysis of Next Generation Sequencing Data.

Noncoding DNA sequences (NCS) have attracted much attention recently due to their functional potentials. Here we attempted to reveal the functional roles of noncoding sequences from the point of view of natural selection that typically indicates the functional potentials of certain genomic elements. We analyzed nearly 37 million single nucleotide polymorphisms (SNPs) of Phase I data of the 1000 Genomes Project. We estimated a series of key parameters of population genetics and molecular evolution to characterize sequence variations of the noncoding genome within and between populations, and identified the natural selection footprints in NCS in worldwide human populations. Our results showed that purifying selection is prevalent and there is substantial constraint of variations in NCS, while positive selectionis more likely to be specific to some particular genomic regions and regional populations. Intriguingly, we observed larger fraction of non-conserved NCS variants with lower derived allele frequency in the genome, indicating possible functional gain of non-conserved NCS. Notably, NCS elements are enriched for potentially functional markers such as eQTLs, TF motif, and DNase I footprints in the genome. More interestingly, some NCS variants associated with diseases such as Alzheimer's disease, Type 1 diabetes, and immune-related bowel disorder (IBD) showed signatures of positive selection, although the majority of NCS variants, reported as risk alleles by genome-wide association studies, showed signatures of negative selection. Our analyses provided compelling evidence of natural selection forces on noncoding sequences in the human genome and advanced our understanding of their functional potentials that play important roles in disease etiology and human evolution.

AB121. NAT2 sequence polymorphisms and acetylation profiles in Indians

Evolutionary study of genes and genomes are helpful in decoding the role played by various evolutionary forces including footprints of natural selection. These forces change the architecture of genes for their best adaption in a particular environment. Inter-individual variations in drug response are responsible for adverse drug reactions, therapeutic drug failure and susceptibility to other diseases, thus understanding the genetic basis of drug metabolization serves as a key to inter-individual drug responses. To this respect, human N-acetyltransferase 2 (NAT2) is a drug metabolizing gene that helps in the metabolism of wide variety of drugs used for treating different diseases. The effective metabolization of exogenous chemicals by NAT2 gene classifies individuals into two acetylator phenotypes; fast (rapid) acetylator and slow acetylator. In order to determine which of the two acetylation phenotypes are prevalent in Indian population, we sequenced NAT2 873 bp coding region in 250 Indian populations collected from six geographical zones (North India, West India, South India, Central India, East India and North East India) and three tribal populations residing in Odisha (East India). On the basis of seven common NAT2 SNPs found in worldwide population, the individuals can be categorized as fast acetylator and slow acetylator. Thus, evolutionary analysis of drug metabolizing gene helps in understanding the metabolism of different therapeutic drugs and exogenous chemicals present in diet. Furthermore, the polymorphisms present in NAT2 gene will be used to understand how the variability of gene has evolved and how it affects the drug response mechanism in Indian populations.

Haplotypic diversity of porcine LEP and LEPR genes involved in growth and fatness regulation.

The analysis of structural genetic variability in candidate genes can make it possible to analyse the selection footprint and deepen the understanding of the genetic basis of complex traits. The leptin (LEP) and its receptor (LEPR) porcine genes are involved in food intake and energy homeostasis, and polymorphisms associated to growth and fatness traits have been detected in both genes. The main objective of this study was to explore the genetic variability of the most polymorphic regions of both genes in a variety of pig populations and wild boars from diverse European and Asian origins. In total, 54 animals were included in the analyses, with a remarkable sampling of Spanish wild boars and Iberian pigs. The sequencing allowed the identification of 69 and 26 polymorphisms in LEP and LEPR genes, respectively. Neighbour-joining trees built for the 69 haplotypes identified in the LEP and the 24 haplotypes detected in the LEPR showed the known genetic divergence between European and Asian pig breeds. A high variability of the LEP was detected in the different analysed populations providing new data for the existence of two domestication centres in Asia. In comparison to the LEP gene, the LEPR showed a lower variability, especially in the Iberian breed that showed no variability. Moreover, results of the Hudson-Kreitman-Aguadé neutrality test support a possible selection event of the LEPR gene region in this breed, potentially related with its leptin resistance pattern and good adaptation to a traditional extensive production system with strong seasonal changes of feeding resources.

A genomic portrait of haplotype diversity and signatures of selection in indigenous southern African populations.

We report a study of genome-wide, dense SNP (∼900K) and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region.

Genome-wide patterns of differentiation and spatially varying selection between postglacial recolonization lineages of Populus alba (Salicaceae), a widespread forest tree.

Studying the divergence continuum in plants is relevant to fundamental and applied biology because of the potential to reveal functionally important genetic variation. In this context, whole-genome sequencing (WGS) provides the necessary rigour for uncovering footprints of selection. We resequenced populations of two divergent phylogeographic lineages of Populus alba (n = 48), thoroughly characterized by microsatellites (n = 317), and scanned their genomes for regions of unusually high allelic differentiation and reduced diversity using > 1.7 million single nucleotide polymorphisms (SNPs) from WGS. Results were confirmed by Sanger sequencing. On average, 9134 high-differentiation (≥ 4 standard deviations) outlier SNPs were uncovered between populations, 848 of which were shared by ≥ three replicate comparisons. Annotation revealed that 545 of these were located in 437 predicted genes. Twelve percent of differentiation outlier genome regions exhibited significantly reduced genetic diversity. Gene ontology (GO) searches were successful for 327 high-differentiation genes, and these were enriched for 63 GO terms. Our results provide a snapshot of the roles of 'hard selective sweeps' vs divergent selection of standing genetic variation in distinct postglacial recolonization lineages of P. alba. Thus, this study adds to our understanding of the mechanisms responsible for the origin of functionally relevant variation in temperate trees.

GC-Content Evolution in Bacterial Genomes: The Biased Gene Conversion Hypothesis Expands

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.

A selective sweep in a Varroa destructor resistant honeybee (Apis mellifera) population

The mite Varroa destructor is one of the most dangerous parasites of the Western honeybee (Apis mellifera) causing enormous colony losses worldwide. Various chemical treatments for the control of the Varroa mite are currently in use, which, however, lead to residues in bee products and often to resistance in mites. This facilitated the exploration of alternative treatment methods and breeding for mite resistant honeybees has been in focus for breeders in many parts of the world with variable results.Another approach has been applied to a honeybee population on Gotland (Sweden) that was exposed to natural selection and survived Varroa-infestation for more than 10years without treatment. Eventually this population became resistant to the parasite by suppressing the reproduction of the mite. A previous QTL mapping study had identified a region on chromosome 7 with major loci contributing to the mite resistance. Here, a microsatellite scan of the significant candidate QTL regions was used to investigate potential footprints of selection in the original population by comparing the study population on Gotland before (2000) and after selection (2007). Genetic drift had caused an extreme loss of genetic diversity in the 2007 population for all genetic markers tested. In addition to this overall reduction of heterozygosity, two loci on chromosome 7 showed an even stronger and significant reduction in diversity than expected from genetic drift alone. Within the selective sweep eleven genes are annotated, one of them being a putative candidate to interfere with reduced mite reproduction. A glucose–methanol–choline oxidoreductase (GMCOX18) might be involved in changing volatiles emitted by bee larvae that might be essential to trigger oogenesis in Varroa.

Signatures of natural selection at the FTO (fat mass and obesity associated) locus in human populations.

Background and aimsPolymorphisms in the first intron of FTO have been robustly replicated for associations with obesity. In the Sorbs, a Slavic population resident in Germany, the strongest effect on body mass index (BMI) was found for a variant in the third intron of FTO (rs17818902). Since this may indicate population specific effects of FTO variants, we initiated studies testing FTO for signatures of selection in vertebrate species and human populations.MethodsFirst, we analyzed the coding region of 35 vertebrate FTO orthologs with Phylogenetic Analysis by Maximum Likelihood (PAML, ω = dN/dS) to screen for signatures of selection among species. Second, we investigated human population (Europeans/CEU, Yoruba/YRI, Chinese/CHB, Japanese/JPT, Sorbs) SNP data for footprints of selection using DnaSP version 4.5 and the Haplotter/PhaseII. Finally, using ConSite we compared transcription factor (TF) binding sites at sequences harbouring FTO SNPs in intron three.ResultsPAML analyses revealed strong conservation in coding region of FTO (ω<1). Sliding-window results from population genetic analyses provided highly significant (p<0.001) signatures for balancing selection specifically in the third intron (e.g. Tajima’s D in Sorbs = 2.77). We observed several alterations in TF binding sites, e.g. TCF3 binding site introduced by the rs17818902 minor allele.ConclusionPopulation genetic analysis revealed signatures of balancing selection at the FTO locus with a prominent signal in intron three, a genomic region with strong association with BMI in the Sorbs. Our data support the hypothesis that genes associated with obesity may have been under evolutionary selective pressure.

Selection footprints in barley breeding lines detected by combining genotyping-by-sequencing with reference genome information

This study is a retrospective analysis of an elite cross from the Spanish National Barley Breeding Program. This was the most successful cross produced in the breeding program in the past 20 years. The progeny from this cross has been investigated at two points in the program, before and after selection, through the analysis of allelic frequencies at a number of genetic loci with molecular markers. Shifts in allelic frequencies after selection allowed the identification of genomic regions with selection footprints likely due to the breeding process. The cross was replicated in three different years, and therefore, the three progenies represent different selection histories but, in all cases, were preferentially selected compared to the lines from other crosses used in the program. The progenies were sampled at two generations, before conscious selection (F2) and after six generations of selection (F8). The F2 plants were genotyped with microsatellites, whereas 31 F8 lines were surveyed for SNP and presence/absence variation polymorphisms using a genotyping-by-sequencing system (DArTseq). The DArTseq markers were aligned to the barley physical map, and, after curation, over 3,000 were still available for the analysis. Overall, 15 genomic regions in the F8 lines had allele frequencies beyond chosen thresholds, indicating selection, eight toward parent Orria and seven toward Plaisant. These selection footprints partially validated QTLs detected through classical linkage mapping in a RIL population of the same cross. These validated selection footprints convey useful information for barley breeding, either through marker-assisted selection or through genomic selection.

Effective Population Size and Signatures of Selection Using Bovine 50K SNP Chips in Korean Native Cattle (Hanwoo).

Inferring the effective population size and the pattern of selection signatures is of interest both from an evolutionary perspective and to improve models for mapping of quantitative trait genes. We used DNA samples of 61 sires and 486 progeny of the Hanwoo, genotyped by the Illumina Bovine SNP50 BeadChip, to analyze the genetic structure. Our study showed a persistent decline in effective population size throughout the period considered, but suggested a marked decline at one distinctive time point (100th generation) and two sharp decline intervals (50th–25th generation and 25th–10th generation). This pattern can be explained by Hanwoo formation and the modern breeding program. Our results revealed 95 regions exhibiting the footprint of recent positive selection at a threshold level of 0.01. We found an overlap of the 11 core regions presenting top P-values and those that had previously been identified as harboring quantitative trait loci from other breeds. The information generated from this study can be used to better understand the mechanism of selection in Hanwoo breeding, and provide important implications for the design and application of association studies in the Hanwoo population.

Inferring positive selection in humans from genomic data.

Adaptation can be described as an evolutionary process that leads to an adjustment of the phenotypes of a population to their environment. In the classical view, new mutations can introduce novel phenotypic features into a population that leave footprints in the genome after fixation, such as selective sweeps. Alternatively, existing genetic variants may become beneficial after an environmental change and increase in frequency. Although they may not reach fixation, they may cause a shift of the optimum of a phenotypic trait controlled by multiple loci. With the availability of polymorphism data from various organisms, including humans and chimpanzees, it has become possible to detect molecular evidence of adaptation and to estimate the strength and target of positive selection. In this review, we discuss the two competing models of adaptation and suitable approaches for detecting the footprints of positive selection on the molecular level.

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints

Oxytocin is a nonapeptide involved in a wide range of physiologic and behavioral functions. Until recently, it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed oxytocin (OXT) in 29 primate species and the oxytocin receptor (OXTR) in 21 of these species. We report here three novel OXT forms in the New World monkeys, as well as a more extensive distribution of a previously described variant (Leu8Pro). In structural terms, these OXTs share the same three low-energy conformations in solution during molecular dynamic simulations, with subtle differences in their side chains. A consistent signal of positive selection was detected in the Cebidae family, and OXT position 8 showed a statistically significant (P = 0.013) correlation with litter size. Several OXTR changes were identified, some of them promoting gain or loss of putative phosphorylation sites, with possible consequences for receptor internalization and desensitization. OXTR amino acid sites are under positive selection, and intramolecular and intermolecular coevolutionary processes with OXT were also detected. We suggest that some New World monkey OXT-OXTR forms can be correlated to male parental care through the increase of cross-reactivity with its correlated vasopressin system.

Tracking footprints of selection associated with soybean adaptation to Central-East Europe environments

The identification of genomic regions affected by phenotypic selection during breeding is important for elucidating the genetic basis of complex traits underlying adaptation to a specific target environment. This study investigated the soybean (Glycine max (L.) Merr.) adaptation in Central-East European environments by a hitchhiking mapping approach and pedigree analysis. Population genetic principles were applied to microsatellite markers using multiple outlier detection tests. The analyzed populations comprised ancestral and elite varieties. Genetic diversity parameters showed significant differences between the populations. Eight markers were considered as strong positive selection candidate loci, indicating regions involved in the adaptation. Bottleneck tests provided no evidence of population bottlenecks for the candidate positive selection loci, suggesting that selection might shaped the pattern of genetic diversity in these regions. Co-localisation of the candidate positive selection loci and previously mapped quantitative trait loci (QTLs) revealed a high level of agreement between the identified QTLs and the traits expected to be under selection during soybean breeding. The identification and differentiation of selectively important QTLs have practical importance for future breeding programs, aiming at developing varieties for a specific target environment.

Population genomic analyses of early‐phase Atlantic Salmon (Salmo salar) domestication/captive breeding

Domestication can have adverse genetic consequences, which may reduce the fitness of individuals once released back into the wild. Many wild Atlantic salmon (Salmo salarL.) populations are threatened by anthropogenic influences, and they are supplemented with captively bred fish. The Atlantic salmon is also widely used in selective breeding programs to increase the mean trait values for desired phenotypic traits. We analyzed a genomewide set of SNPs in three domesticated Atlantic salmon strains and their wild conspecifics to identify loci underlying domestication. The genetic differentiation between domesticated strains and wild populations was low (FST < 0.03), and domesticated strains harbored similar levels of genetic diversity compared to their wild conspecifics. Only a few loci showed footprints of selection, and these loci were located in different linkage groups among the different wild population/hatchery strain comparisons. Simulated scenarios indicated that differentiation in quantitative trait loci exceeded that in neutral markers during the early phases of divergence only when the difference in the phenotypic optimum between populations was large. This study indicates that detecting selection using standard approaches in the early phases of domestication might be challenging unless selection is strong and the traits under selection show simple inheritance patterns.

Diapause induction and relaxed selection on alternative developmental pathways in a butterfly.

Seasonal phenotypic plasticity entails differential trait expression depending on the time of season. The facultative induction of winter diapause in temperate insects is a developmental switch mechanism often leading to differential expression in life-history traits. However, when there is a latitudinal shift from a bivoltine to univoltine life cycle, selection for pathway-specific expression is disrupted, which may allow drift towards less optimal trait values within the non-selected pathway. We use field- and experimental data from five Swedish populations of Pararge aegeria to investigate latitudinal variation in voltinism, local adaptation in the diapause switch and footprints of selection on pathway-specific regulation of life-history traits and sexual dimorphism in larval development. Field data clearly illustrated how natural populations gradually shift from bivoltinism to univoltinism as latitude increases. This was supported experimentally as the decrease in direct development at higher latitudes was accompanied by increasing critical daylengths, suggesting local adaptation in the diapause switch. The differential expression among developmental pathways in development time and growth rate was significantly less pronounced in univoltine populations. Univoltine populations showed no significant signs of protandry during larval development, suggesting that erosion of the direct development pathway under relaxed selection has led to the loss of its sex-specific modifications.

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G.

Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive properties modulating the activity of many immune system cells, and polymorphisms observed at the HLA-G 5' upstream regulatory region (5'URR) may influence gene transcriptional regulation. In this study, we characterized the sequence variation and haplotype structure of the HLA-G 5'URR in worldwide populations to investigate the evolutionary history of the HLA-G promoter and shed some light into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region, encompassing the known HLA-G regulatory elements, was sequenced in three African populations from Senegal, Benin and Congo, and data were combined with those available in the literature, resulting in a total of 1411 individuals from 21 worldwide populations. High levels of nucleotide and haplotype diversities, excess of intermediate-frequency variants and reduced population differentiation were observed at this locus when compared with the background genomic variation. These features support a strong molecular signature of balancing selection at HLA-G 5'URR, probably as a result of the competing needs to maintain both a maternal-fetal immune tolerance and an efficient host immune response to invading pathogens during human evolution. An extended analysis of a 300-kb region surrounding HLA-G revealed that this region is not involved in a hitchhiking effect and may be the direct target of selection.

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.