Identification of potential obese-specific biomarkers and pathways associated with abdominal subcutaneous fat deposition in pig using a comprehensive bioinformatics strategy.

Abdominal subcutaneous fat deposition (ASFD) is not only related to meat quality in the pig industry but also to human health in medicine. It is of great value to elucidate the potential molecular mechanisms of ASFD. The present study aims to identify obese-specific biomarkers and key pathways correlated with ASFD in pigs. The ASF-related mRNA expression dataset GSE136754 was retrieved from the Gene Expression Omnibus (GEO) database and systematically analyzed using a comprehensive bioinformatics method. A total of 565 differentially expressed genes (DEGs) were identified between three obese and three lean pigs, and these DEGs were mainly involved in the p53 signaling pathway, MAPK signaling pathway and fatty acid metabolism. A protein-protein interaction (PPI) network, consisting of 540 nodes and 1,065 edges, was constructed, and the top ten genes with the highest degree scores-ABL1, HDAC1, CDC42, HDAC2, MRPS5, MRPS10, MDM2, JUP, RPL7L1 and UQCRFS1-were identified as hub genes in the whole PPI network. Especially HDAC1, MDM2, MRPS10 and RPL7L1 were identified as potential robust obese-specific biomarkers due to their significant differences in single gene expression levels and high ROC area; this was further verified by quantitative real-time PCR (qRT-PCR) on abdominal subcutaneous fat samples from obese-type (Saba) and lean-type (Large White) pigs. Additionally, a mRNA-miRNA-lncRNA ceRNA network consisting of four potential biomarkers, 15 miRNAs and 51 lncRNAs was established, and two targeted lncRNAs with more connections, XIST and NEAT1, were identified as potentially important regulatory factors. The findings of this study may provide novel insights into the molecular mechanism involved in ASFD.

Genome-wide identification of quantitative trait loci and candidate genes for seven carcass traits in a four-way intercross porcine population.

BACKGROUND: Carcass traits are essential economic traits in the commercial pig industry. However, the genetic mechanism of carcass traits is still unclear. In this study, we performed a genome-wide association study (GWAS) based on the specific-locus amplified fragment sequencing (SLAF-seq) to study seven carcass traits on 223 four-way intercross pigs, including dressing percentage (DP), number of ribs (RIB), skin thinkness (ST), carcass straight length (CSL), carcass diagonal length (CDL), loin eye width (LEW), and loin eye thickness (LET). RESULTS: A total of 227,921 high-quality single nucleotide polymorphisms (SNPs) were detected to perform GWAS. A total of 30 SNPs were identified for seven carcass traits using the mixed linear model (MLM) (p < 1.0 × 10- 5), of which 9 SNPs were located in previously reported quantitative trait loci (QTL) regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43 to 16.32%. Furthermore, 11 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs. CONCLUSIONS: The GWAS results will improve our understanding of the genetic basis of carcass traits. We hypothesized that the candidate genes associated with these discovered SNPs would offer a biological basis for enhancing the carcass quality of pigs in swine breeding.

Identification of potential tissue-specific biomarkers involved in pig fat deposition through integrated bioinformatics analysis and machine learning.

Backfat thickness (BT) and intramuscular fat (IMF) content are closely appertained to meat production and quality in pig production. Deposition in subcutaneous adipose (SA) and IMF concerns different genes and regulatory mechanisms. And larger studies with rigorous design should be carried to explore the molecular regulation of fat deposition in different tissues. The purpose of this study is to gain a better understanding of the molecular mechanisms underlying differences in fat deposition among different tissues and identify tissue-specific genes involved in regulating fat deposition. The SA-associated datasets (GSE122349 and GSE145956) and IMF-associated datasets (GSE165613 and GSE207279) were downloaded from the Gene Expression Omnibus (GEO) as the BT and IMF group, respectively. Subsequently, the Robust Rank Aggregation (RRA) algorithm identified 27 down- and 29 up-regulated differentially expressed genes (DEGs) in the BT group. Based on bioinformatics and three machine learning algorithms, four SA deposition-related potential biomarkers, namely ACLY, FASN, ME1, and ARVCF were selected. FASN was evaluated as the most valuable biomarker for the SA mechanism. The 18 down- and 34 up-regulated DEGs in the IMF group were identified, and ACTA2 and HMGCL were screened as the IMF deposition-related candidate core genes, especially the ACTA2 may play the critical role in IMF deposition regulation. Moreover, based on the constructed ceRNA network, we postulated that the role of predicted ceRNA interaction network of XIST, NEAT1/miR-15a-5p, miR-16-5p, miR-424-5p, miR-497-5p/FASN were vital in the SA metabolism, XIST, NEAT1/miR-27a/b-3p, 181a/c-5p/ACTA2 might contribute to the regulation to IMF metabolism, which all gave suggestions in molecular mechanism for regulation of fat deposition. These findings may facilitate advancements in porcine quality at the genetic and molecular levels and assist with human obesity-associated diseases.

Genome-wide single nucleotide polymorphism (SNP) data reveal potential candidate genes for litter traits in a Yorkshire pig population.

The litter trait is one of the most important economic traits, and increasing litter size is of great economic value in the pig industry. However, the molecular mechanisms underlying pig litter traits remain elusive. To identify molecular markers and candidate genes for pig litter traits, a genome-wide association study (GWAS) and selection signature analysis were conducted in a Yorkshire pig population. A total of 518 producing sows were genotyped with Illumina Porcine SNP 50 BeadChip, and 1969 farrowing records for the total number born (TNB), the number born alive (NBA), piglets born dead (PBD), and litter weight born alive (LWB) were collected. Then, a GWAS was performed for the four litter traits using a repeatability model. Based on the estimated breeding values (EBVs) of TNB, 15 high- and 15 low-prolificacy individuals were selected from the 518 sows to implement selection signature analysis. Subsequently, the selection signatures affecting the litter traits of sows were detected by using two methods including the fixation index (FST) and θπ. Combining the results of the GWAS and selection signature analysis, 20 promising candidate genes (NKAIN2, IGF1R, KISS1R, TYRO3, SPINT1, ADGRF5, APC2, PTBP1, CLCN3, CBR4, HPF1, FAM174A, SCP2, CLIC1, ZFYVE9, SPATA33, KIF5C, EPC2, GABRA2, and GABRA4) were identified. These findings provide novel insights into the genetic basis of pig litter traits and will be helpful for improving the reproductive performances of sows in pig breeding.

Identification of Potential Sex-Specific Biomarkers in Pigs with Low and High Intramuscular Fat Content Using Integrated Bioinformatics and Machine Learning.

Intramuscular fat (IMF) content is a key determinant of pork quality. Controlling the genetic and physiological factors of IMF and the expression patterns of various genes is important for regulating the IMF content and improving meat quality in pig breeding. Growing evidence has suggested the role of genetic factors and breeds in IMF deposition; however, research on the sex factors of IMF deposition is still lacking. The present study aimed to identify potential sex-specific biomarkers strongly associated with IMF deposition in low- and high-IMF pig populations. The GSE144780 expression dataset of IMF deposition-related genes were obtained from the Gene Expression Omnibus. Initially, differentially expressed genes (DEGs) were detected in male and female low-IMF (162 DEGs, including 64 up- and 98 down-regulated genes) and high-IMF pigs (202 DEGs, including 147 up- and 55 down-regulated genes). Moreover, hub genes were screened via PPI network construction. Furthermore, hub genes were screened for potential sex-specific biomarkers using the least absolute shrinkage and selection operator machine learning algorithm, and sex-specific biomarkers in low-IMF (troponin I (TNNI1), myosin light chain 9(MYL9), and serpin family C member 1(SERPINC1)) and high-IMF pigs (CD4 molecule (CD4), CD2 molecule (CD2), and amine oxidase copper-containing 2(AOC2)) were identified, and then verified by quantitative real-time PCR (qRT-PCR) in semimembranosus muscles. Additionally, the gene set enrichment analysis and single-sample gene set enrichment analysis of hallmark gene sets were collectively performed on the identified biomarkers. Finally, the transcription factor-biomarker and lncRNA-miRNA-mRNA (biomarker) networks were predicted. The identified potential sex-specific biomarkers may provide new insights into the molecular mechanisms of IMF deposition and the beneficial foundation for improving meat quality in pig breeding.

Genome-wide association study reveals genetic loci and candidate genes for meat quality traits in a four-way crossbred pig population.

Meat quality traits (MQTs) have gained more attention from breeders due to their increasing economic value in the commercial pig industry. In this genome-wide association study (GWAS), 223 four-way intercross pigs were genotyped using the specific-locus amplified fragment sequencing (SLAF-seq) and phenotyped for PH at 45 min post mortem (PH45), meat color score (MC), marbling score (MA), water loss rate (WL), drip loss (DL) in the longissimus muscle, and cooking loss (CL) in the psoas major muscle. A total of 227, 921 filtered single nucleotide polymorphisms (SNPs) evenly distributed across the entire genome were detected to perform GWAS. A total of 64 SNPs were identified for six meat quality traits using the mixed linear model (MLM), of which 24 SNPs were located in previously reported QTL regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43% to 16.32%. The genomic heritability estimates based on SNP for six meat-quality traits were low to moderate (0.07-0.47) being the lowest for CL and the highest for DL. A total of 30 genes located within 10 kb upstream or downstream of these significant SNPs were found. Furthermore, several candidate genes for MQTs were detected, including pH45 (GRM8), MC (ANKRD6), MA (MACROD2 and ABCG1), WL (TMEM50A), CL (PIP4K2A) and DL (CDYL2, CHL1, ABCA4, ZAG and SLC1A2). This study provided substantial new evidence for several candidate genes to participate in different pork quality traits. The identification of these SNPs and candidate genes provided a basis for molecular marker-assisted breeding and improvement of pork quality traits.

Signatures of selection in indigenous Chinese cattle genomes reveal adaptive genes and genetic variations to cold climate.

Cold climate shapes the genome of animals and drives them to carry sufficient genetic variations to adapt to changes in temperature. However, limited information is available about the genome-wide pattern of adaptations to cold environments in cattle. In the present study, we used 777K SNP genotyping (15 Chinese cattle breeds, 198 individuals) and whole genome resequencing data (54 cattle breeds of the world, 432 individuals) to disentangle divergent selection signatures, especially between the cold-adapted (annual average temperature of habitat, 6.24 °C to 10.3 °C) and heat-adapted (20.2 °C to 24.73 °C) Chinese native cattle breeds. Genomic analyses revealed a set of candidate genes (e.g., UQCR11, DNAJC18, EGR1, and STING1) were functionally associated with thermogenesis and energy metabolism. We also characterized the adaptive loci of cattle exposed to cold temperatures. Our study finds new candidate genes and provides new insights into adaptations to cold climates in cattle.

Cold climates can affect cattle performance, survival, and health. Local cattle breeds have been adapted to the local environments including extremely cold temperatures after a long period of natural and artificial selection. Selection and local adaptation are shaping populations. However, identifying loci associated with cold adaptation has been a major challenge. We used high-density SNP arrays and resequencing data to comprehensively analyze and compare the genomic selection signatures of Chinese northern and southern cattle, and elucidated several adaptive genes and alleles involved in cold adaptation. The complexity of genetic adaptation mechanism among different low-temperature adapted cattle breeds was also emphasized.

Genome-Wide Association Study of Growth Traits in a Four-Way Crossbred Pig Population.

Growth traits are crucial economic traits in the commercial pig industry and have a substantial impact on pig production. However, the genetic mechanism of growth traits is not very clear. In this study, we performed a genome-wide association study (GWAS) based on the specific-locus amplified fragment sequencing (SLAF-seq) to analyze ten growth traits on 223 four-way intercross pigs. A total of 227,921 highly consistent single nucleotide polymorphisms (SNPs) uniformly dispersed throughout the entire genome were used to conduct GWAS. A total of 53 SNPs were identified for ten growth traits using the mixed linear model (MLM), of which 18 SNPs were located in previously reported quantitative trait loci (QTL) regions. Two novel QTLs on SSC4 and SSC7 were related to average daily gain from 30 to 60 kg (ADG30-60) and body length (BL), respectively. Furthermore, 13 candidate genes (ATP5O, GHRHR, TRIM55, EIF2AK1, PLEKHA1, BRAP, COL11A2, HMGA1, NHLRC1, SGSM1, NFATC2, MAML1, and PSD3) were found to be associated with growth traits in pigs. The GWAS findings will enhance our comprehension of the genetic architecture of growth traits. We suggested that these detected SNPs and corresponding candidate genes might provide a biological foundation for improving the growth and production performance of pigs in swine breeding.

Genome-wide association study identifying genetic variants associated with carcass backfat thickness, lean percentage and fat percentage in a four-way crossbred pig population using SLAF-seq technology.

BACKGROUND: Carcass backfat thickness (BFT), carcass lean percentage (CLP) and carcass fat percentage (CFP) are important to the commercial pig industry. Nevertheless, the genetic architecture of BFT, CLP and CFP is still elusive. Here, we performed a genome-wide association study (GWAS) based on specific-locus amplified fragment sequencing (SLAF-seq) to analyze seven fatness-related traits, including five BFTs, CLP, and CFP on 223 four-way crossbred pigs. RESULTS: A total of 227, 921 highly consistent single nucleotide polymorphisms (SNPs) evenly distributed throughout the genome were used to perform GWAS. Using the mixed linear model (MLM), a total of 20 SNP loci significantly related to these traits were identified on ten Sus scrofa chromosomes (SSC), of which 10 SNPs were located in previously reported quantitative trait loci (QTL) regions. On SSC7, two SNPs (SSC7:29,503,670 and rs1112937671) for average backfat thickness (ABFT) exceeded 1% and 10% Bonferroni genome-wide significance levels, respectively. These two SNP loci were located within an intron region of the COL21A1 gene, which was a protein-coding gene that played an important role in the porcine backfat deposition by affecting extracellular matrix (ECM) remodeling. In addition, based on the other three significant SNPs on SSC7, five candidate genes, ZNF184, ZNF391, HMGA1, GRM4 and NUDT3 were proposed to influence BFT. On SSC9, two SNPs for backfat thickness at 6-7 ribs (67RBFT) and one SNP for CLP were in the same locus region (19 kb interval). These three SNPs were located in the PGM2L1 gene, which encoded a protein that played an indispensable role in glycogen metabolism, glycolysis and gluconeogenesis as a key enzyme. Finally, one significant SNP on SSC14 for CLP was located within the PLBD2 gene, which participated in the lipid catabolic process. CONCLUSIONS: A total of two regions on SSC7 and SSC9 and eight potential candidate genes were found for fatness-related traits in pigs. The results of this GWAS based on SLAF-seq will greatly advance our understanding of the genetic architecture of BFT, CLP, and CFP traits. These identified SNP loci and candidate genes might serve as a biological basis for improving the important fatness-related traits of pigs.

Identification of key sex-specific pathways and genes in the subcutaneous adipose tissue from pigs using WGCNA method.

BACKGROUND: Adipose tissues (ATs), including visceral ATs (VATs) and subcutaneous ATs (SATs), are crucial for maintaining energy and metabolic homeostasis. SATs have been found to be closely related to obesity and obesity-induced metabolic disease. Some studies have shown a significant association between subcutaneous fat metabolism and sexes. However, the molecular mechanisms for this association are still unclear. Here, using the pig as a model, we investigated the systematic association between the subcutaneous fat metabolism and sexes, and identified some key sex-specific pathways and genes in the SATs from pigs. RESULTS: The results revealed that 134 differentially expressed genes (DEGs) were identified in female and male pigs from the obese group. A total of 17 coexpression modules were detected, of which six modules were significantly correlated with the sexes (P < 0.01). Among the significant modules, the greenyellow module (cor = 0.68, P < 9e-06) and green module (cor = 0.49, P < 0.003) were most significantly positively correlated with the male and female, respectively. Functional analysis showed that one GO term and four KEGG pathways were significantly enriched in the greenyellow module while six GO terms and six KEGG pathways were significantly enriched in the green module. Furthermore, a total of five and two key sex-specific genes were identified in the two modules, respectively. Two key sex-specific pathways (Ras-MAPK signaling pathway and type I interferon response) play an important role in the SATs of males and females, respectively. CONCLUSIONS: The present study identified some key sex-specific pathways and genes in the SATs from pigs, which provided some new insights into the molecular mechanism of being involved in fat formation and immunoregulation between pigs of different sexes. These findings may be beneficial to breeding in the pig industry and obesity treatment in medicine.

The complete mitochondrial genome of Sinocyclocheilus aluensis (Cyprinoidea: Cyprinidae).

We describe the complete mitochondrial genome of the endangered fish Sinocyclocheilus aluensis. It is a circular molecule of 16,583 bp in size with a D-loop region and contains 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 13 protein-coding genes, and all genes show the typical gene arrangement conforming to the vertebrate consensus. The overall base composition of S. aluensis mitogenome is 31.1% for A, 26.9% for C, 16.6% for G, and 25.4% for T. The percentage of G + C content is 43.5%. Phylogenetic analysis demonstrated that all Sinocyclocheilus species clustered together and formed a monophyletic group. The mitochondrial genome sequencing for S. aluensis in this study provides important molecular data for further evolutionary research for Sinocyclocheilus.

Genetic Diversity and Selection Signatures Within Diannan Small-Ear Pigs Revealed by Next-Generation Sequencing.

Genetic characterization of Chinese indigenous pig breeds is essential to promote scientific conservation and sustainable development of pigs. Here, we systematically surveyed the genomes of 75 unrelated Diannan small-ear (DSE) pigs from three diverse regions (Yingjiang County, Jinping County, and Sipsongpanna in Yunnan Province) to describe their population structures, genetic diversity, inbreeding coefficients, and selection signatures. First, these individuals were sequenced and genotyped using the genome reducing and sequencing (GGRS) protocol. A total of 438,038 autosomal single-nucleotide polymorphisms (SNPs) were obtained and used for subsequent statistical analysis. The results showed that these DSE pigs were clearly differentiated into three separate clades revealed by the population structure and principal component analysis, which is consistent with their geographical origins. Diannan small-ear pigs owned lower genetic diversity when compared with some other pig breeds, which demonstrated the need to strengthen the conservation strategies for DSE pigs. In addition, the inbreeding coefficients based on runs of homozygosity (ROH) length (F ROH) were calculated in each ROH length categories, respectively. And the results indicated that the ancient (up to 50 generations ago) inbreeding had greater impacts than recent (within the last five generations) inbreeding within DSE pigs. Some candidate selection signatures within the DSE pig population were detected through the ROH islands and integrated haplotype homozygosity score (iHS) methods. And genes associated with meat quality (COL15A1, RPL3L, and SLC9A3R2), body size (PALM2-AKAP2, NANS, TRAF7, and PACSIN1), adaptability (CLDN9 and E4F1), and appetite (GRM4) were identified. These findings can help to understand the genetic characteristics and provide insights into the molecular background of special phenotypes of DSE pigs to promote conservation and sustainability of the breed.

Natural selection on TMPRSS6 associated with the blunted erythropoiesis and improved blood viscosity in Tibetan pigs.

Tibetan pigs, indigenous to Tibetan plateau, are well adapted to hypoxia. So far, there have been not any definitively described genes and functional sites responsible for hypoxia adaptation for the Tibetan pig. The whole genome-wide association studies in human suggested that genetic variations in TMPRSS6 was associated with hemoglobin concentration (HGB) and red cell counts (RBC). Here we conducted resequencing of the nearly entire genomic region (40.1 kb) of the candidate gene TMPRSS6 in 40 domestic pigs and 40 wild boars along continuous altitudes and identified 708 SNPs, in addition to an indel (CGTG/----) in the intron 10. We conduct the CGTG indel in 838 domestic pigs, both the CGTG deletion frequency and the pairwise r2 linkage disequilibrium showed an increase with elevated altitudes, suggesting that TMPRSS6 has been under Darwinian positive selection. As the conserved core sequence of hypoxia-response elements (HREs), the deletion of CGTG in Tibetan pigs decreased the expression levels of TMPRSS6 mRNA and protein in the liver revealed by real-time quantitative PCR and western blot, respectively. We compared domestic pigs and Tibetan pigs living continuous altitudes, found that the blood-related traits with the increase of altitude, however, the HGB did not increase with the elevation in Tibetan pigs. Genotype association analysis results dissected a genetic effect on reducing HGB by 13.25 g/L in Gongbo'gyamda Tibetan pigs, decreasing mean corpuscular volume (MCV) by 4.79 fl in Diqing Tibetan pigs. In conclusion, the CGTG deletion of TMPRSS6 resulted in lower HGB and smaller MCV, which could reflect a blunting erythropoiesis and improving blood viscosity as well as erythrocyte deformability. It remains to be determined whether a blunting of erythropoiesis for TMPRSS6 or others genetic effects are the physiological adaptations among Tibetan pigs.

The complete mitochondrial genome of Pareuchiloglanis myzostoma (Teleostei, Siluriformes).

Pareuchiloglanis myzostoma is a key-listed protected indigenous fish species in Nujiang, Yunnan, China. In this study, we firstly reported the complete mitochondrial genome of P. myzostoma, which was 16,584 bp in length, containing 13 protein-coding genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). The overall base composition of P. myzostoma was 30.7% for A, 24.2% for T, 16.0% for G, and 29.1% for C. Phylogenetic analysis showed that all Sisoridae species clustered together formed a monophyletic group. This work would provide a set of useful data on further molecular evolution studies of this precious species.

Genome-Wide and Trait-Specific Markers: A Perspective in Designing Conservation Programs.

Nowadays, breed conservation has entered the genomics era and it is imperative to develop novel theory to design the breeding schemes of the conservation populations by using the genomic information. The genome-wide markers have been regarded as a useful strategy to maintain genetic diversity. However, using the genome-wide SNPs to optimize diversity might not be optimal for some specific loci associated with specific-traits. Using the sequencing data of the conserved population of the Saba pig breed, we demonstrated that the conservation program designed by using the genome-wide SNPs might result in the loss of the genetic diversity of the reproduction trait. We suggested an idea of using phylogenetic tree to select valuable individuals for conservation program based on the genome-wide and trait-specific makers. The selection rule was to make the selected samples to be widely distributed as much as possible in both the genome-wide and trait-specific phylogenetic trees.

Gene Co-Expression Network Analysis Unraveling Transcriptional Regulation of High-Altitude Adaptation of Tibetan Pig.

Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude. A total of 3,066 DEGs were identified and this list was over-represented for the ontology terms including metabolic process, catalytic activity, and KEGG pathway including metabolic pathway and PI3K-Akt signaling pathway. The regulatory (RIF) and phenotypic (PIF) impact factor analysis identified several known and several potentially novel regulators of hypoxia adaption, including: IKBKG, KLF6 and RBPJ (RIF1), SF3B1, EFEMP1, HOXB6 and ATF6 (RIF2). These findings provide new details of the regulatory architecture of hypoxia-adaptive genes and also insight into which genes may undergo epigenetic modification for further study in the high-altitude adaptation.

Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia.

The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaptation to high altitude in dogs, we performed whole-genome sequencing of 60 dogs including five breeds living at continuous altitudes along the Tibetan Plateau from 800 to 5100 m as well as one European breed. More than 150× sequencing coverage for each breed provides us with a comprehensive assessment of the genetic polymorphisms of the dogs, including Tibetan Mastiffs. Comparison of the breeds from different altitudes reveals strong signals of population differentiation at the locus of hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) and beta hemoglobin cluster. Notably, four novel nonsynonymous mutations specific to high-altitude dogs are identified at EPAS1, one of which occurred at a quite conserved site in the PAS domain. The association testing between EPAS1 genotypes and blood-related phenotypes on additional high-altitude dogs reveals that the homozygous mutation is associated with decreased blood flow resistance, which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also identified as a selective target in Tibetan highlanders, though no amino acid changes were found. Thus, our results not only indicate parallel evolution of humans and dogs in adaptation to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.

The local origin of the Tibetan pig and additional insights into the origin of Asian pigs.

BACKGROUND: The domestic pig currently indigenous to the Tibetan highlands is supposed to have been introduced during a continuous period of colonization by the ancestors of modern Tibetans. However, there is no direct genetic evidence of either the local origin or exotic migration of the Tibetan pig. METHODS AND FINDINGS: We analyzed mtDNA hypervariable segment I (HVI) variation of 218 individuals from seven Tibetan pig populations and 1,737 reported mtDNA sequences from domestic pigs and wild boars across Asia. The Bayesian consensus tree revealed a main haplogroup M and twelve minor haplogroups, which suggested a large number of small scale in situ domestication episodes. In particular, haplogroups D1 and D6 represented two highly divergent lineages in the Tibetan highlands and Island Southeastern Asia, respectively. Network analysis of haplogroup M further revealed one main subhaplogroup M1 and two minor subhaplogroups M2 and M3. Intriguingly, M2 was mainly distributed in Southeastern Asia, suggesting for a local origin. Similar with haplogroup D6, M3 was mainly restricted in Island Southeastern Asia. This pattern suggested that Island Southeastern Asia, but not Southeastern Asia, might be the center of domestication of the so-called Pacific clade (M3 and D6 here) described in previous studies. Diversity gradient analysis of major subhaplogroup M1 suggested three local origins in Southeastern Asia, the middle and downstream regions of the Yangtze River, and the Tibetan highlands, respectively. CONCLUSIONS: We identified two new origin centers for domestic pigs in the Tibetan highlands and in the Island Southeastern Asian region.

Effects of marker-assisted selection under different initial frequency of QTL favorable allele.

A ten-generation continuous selection experiment on a single trait in a closed population was carried out by stochastic simulation. It assumed that the trait was controlled by polygenes and a single autosomal bi-allelic marked quantitative trait locus (QTL). Individual breeding values were estimated through animal model marker-assisted best linear unbiased prediction (MB-LUP), and breeding animals were selected according to their breeding values. The effects of three levels initial frequencies of QTL favorable allele on marker-assisted selection (MAS) were studied. The results showed that it would gain higher genetic response when implementing MAS on those traits with lower initial frequency of QTL favorable allele. When the initial frequency of QTL favorable allele was low, although the generation number required for fixing QTL favorable allele in the population would be lengthened, its frequency would be increased faster. However, the initial frequency of QTL favorable allele had little effects on the inbreeding rates.

Primary factors affecting the evaluation accuracy of animal model MBLUP.

Marker-assisted best linear unbiased prediction (MBLUP) is one important method of implementing marker-assisted selection (MAS). The computer stochastic simulation method was used to study the effects of heritability of trait, QTL variance and map distance between two adjacent markers on the evaluation accuracy of animal model MBLUP. With the higher heritability, the smaller QTL variance and the shorter map distance between two adjacent markers, the evaluation accuracy of animal model MBLUP would be increased. On the contrary, the evaluation accuracy of animal model MBLUP would be decreased when the heritability was lower, QTL variance was larger and map distance between two adjacent markers was longer.