基于SNP芯片的海南猪全基因组选择信号分析

doi:10.11843/j.issn.0366-6964.2022.02.003

摘要/Abstract

摘要： 旨在通过检测海南猪全基因组上的选择信号，以挖掘与海南猪重要经济性状相关的候选基因，并解析讨论海南猪在进化驯化历史中的受选择情况。本研究利用68头海南猪的GeneSeek Genomic Profiler Procine SNP 80K芯片数据，使用整合单倍型分数（integrated haplotype score，iHS）的方法进行全基因组选择信号检测，并进行了全基因组长片段纯合（runs of homozygosity，ROH）检测分析；以"标准化iHS分数>1.96（P<0.05）"为阈值筛选候选位点，并向上、下游各延伸200 kb作为iHS方法检测到的候选区域，定义其中与ROH检测得到的片段发生"完全重叠"的区段为潜在受选择区域。为进一步探索海南猪选择信号的生物学功能，本研究进行了包含基因注释、QTL（quantitative trait locus）探索和富集分析在内的生物信息学分析。该研究对经过质量控制后剩余的44 578个SNPs，使用iHS方法共检测到395个潜在受选择位点，检测得到172个ROH片段，获得136个潜在受选择区域，注释到469个候选基因。对潜在受选择区域进行QTLs探索分析，结果揭示了海南猪的选择信号多与其肉质性状、生长性状、抗病性状相关；此外，与海南猪的初情期启动日龄相关的QTL主要被报道与SSC12（Sus Scrofa chromosome 12）上的潜在受选择区域重叠。此外，通过候选基因的GO（gene ontology）和KEGG（kyoto encyclopedia of genes and genomes）通路富集分析发现，有91个候选基因在21项功能条目（P<0.05）上显著富集，主要集中在生长代谢、免疫应答和雌激素信号通路相关的条目上。本研究揭示了海南猪群体在其驯化历史上可能受到的选择情况。研究表明，在海南猪全基因组范围内进行选择信号检测，有助于进一步了解海南猪的进化历史及其重要经济性状的遗传机制，在一定程度上为华南型地方猪种种质资源的保存利用和相关研究提供参考。

关键词: 海南猪, 选择信号, SNP, iHS, ROH

Abstract: The purpose of this study was to screen the selection signatures on the whole genome of Hainan pigs, discover the candidate genes of the important economical traits, and analyze the selected process of Hainan pigs in the history of evolution and domestication. Based on the GeneSeek Genomic Profiler (GGP) Procine SNP 80K BeadChip genotypes of 68 Hainan pigs, the integrated haplotype score (iHS) method was carried out to detect the selection signatures for Hainan pigs across the whole genome, and the runs of homozygosity (ROH) analysis was employed. The SNPs with Standard iHS scores > 1.96 (P<0.05) were used as candidate SNPs, and candidate regions detected by iHS were the 200 kb window around the candidate SNPs. In this analysis, the completely overlapping candidate regions detected by both iHS and ROH were defined as potential selected regions. To further explore the biological functions of the selection signatures on Hainan pigs, bioinformatics analysis including gene annotation, quantitative trait locus (QTL) analysis and enrichment analysis were applied. In this study, a total of 44 578 SNPs was remained after quality control. Moreover, 395 candidate selected SNPs were detected by iHS method, 172 ROH segments were detected. And 469 candidate genes were annotated totally in the 136 potential selected regions overlapped. The QTL analysis of the potential selected regions showed that selection signatures of Hainan pigs were associated with meat quality, growth and disease resistance traits. In addition, the QTLs associated with the age of puberty were mostly reported to be overlapped with the potential selected regions on the SSC12 (Sus Scrofa chromosome 12). Moreover, enrichment analysis of gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway of candidate genes showed that 91 candidate genes were significantly enriched in 21 function (P<0.05) terms totally, which were mainly associated with growth and metabolism, immunoresponse and estrogen signaling pathway. This study reveals the possible selection process of Hainan pigs populations in their domestication history. This research suggests that screening the selection signatures on the whole genome of Hainan pigs contributes to a better understanding of the evolution progress and the genetic mechanisms of the important traits, which also provides reference for further analysis about protection and utilization of germplasm resource and related research about southern China pig breeds.

Key words: Hainan pigs, selection signatures, SNP, iHS, ROH

中图分类号:

S828.2

冯雪燕, 刁淑琪, 刘玉强, 徐志婷, 魏趁, 袁晓龙, 李加琪, 张哲. 基于SNP芯片的海南猪全基因组选择信号分析[J]. 畜牧兽医学报, 2022, 53(2): 349-359.

FENG Xueyan, DIAO Shuqi, LIU Yuqiang, XU Zhiting, WEI Chen, YUAN Xiaolong, LI Jiaqi, ZHANG Zhe. Analysis of Selection Signatures for Hainan Pigs across the Whole Genome Based on SNP BeadChips[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(2): 349-359.

参考文献 48

[1]	国家畜禽遗传资源委员会.中国畜禽遗传资源志:猪志[M].北京:中国农业出版社,2011.China National Commission of Animal Genetic Resources.Animal genetic resources in China:pigs[M].Beijing:China Agriculture Press,2011.(in Chinese)
[2]	SABETI P C,VARILLY P,FRY B,et al.Genome-wide detection and characterization of positive selection in human populations[J].Nature,2007,449(7164):913-918.
[3]	BISWAS S,AKEY J M.Genomic insights into positive selection[J].Trends Genet,2006,22(8):437-446.
[4]	MA Y L,ZHANG S X,ZHANG K L,et al.Genomic analysis to identify signatures of artificial selection and loci associated with important economic traits in Duroc pigs[J].G3(Bethesda),2018,8(11):3617-3625.
[5]	LEE Y S,SHIN D,WON K H,et al.Genome-wide scans for detecting the selection signature of the Jeju-island native pig in Korea[J].Asian-Australas J Anim Sci,2020,33(4):539-546.
[6]	吴林慧,孙琦,王荔茹,等.恩施黑猪基因组群体遗传学参数的估计与选择信号研究[J].畜牧兽医学报,2019,50(3):485-494.WU L H,SUN Q,WANG L R,et al.A study of the population genetics parameters and selection signatures in Enshi Black pig[J].Acta Veterinaria et Zootechnica Sinica,2019,50(3):485-494.(in Chinese)
[7]	MA Y L,GU L T,YANG L B,et al.Identifying artificial selection signals in the chicken genome[J].PLoS One,2018,13(4):e0196215.
[8]	韩威,朱云芬,殷建玫,等.基于RAD-seq简化基因组测序的19个地方鸡种遗传进化研究[J].畜牧兽医学报, 2020, 51(4):670-678.HAN W,ZHU Y F,YIN J M,et al.Study on genetic evolution of 19 indigenous chicken breeds based on RAD-seq[J].Acta Veterinaria et Zootechnica Sinica,2020,51(4):670-678.(in Chinese)
[9]	WU D D,YANG C P,WANG M S,et al.Convergent genomic signatures of high-altitude adaptation among domestic mammals[J].Natl Sci Rev,2020,7(6):952-963.
[10]	CHEN M H,PAN D F,REN H Y,et al.Identification of selective sweeps reveals divergent selection between Chinese Holstein and Simmental cattle populations[J].Genet Sel Evol,2016,48(1):76.
[11]	金美林,陆健,费晓娟,等.全基因组选择信号揭示绒山羊绒毛性状相关的候选基因[J].畜牧兽医学报, 2020,51(12):2991-3000.JIN M L,LU J,FEI X J,et al.Genome-wide selection signals reveal candidate genes associated with the cashmere traits of cashmere goats[J].Acta Veterinaria et Zootechnica Sinica,2020,51(12):2991-3000.(in Chinese)
[12]	LIU L L,FANG C,LIU W J.Identification on novel locus of dairy traits of Kazakh horse in Xinjiang[J].Gene,2018,677:105-110.
[13]	李秀领,杨松柏,唐中林,等.大白猪和通城猪全基因组选择性清扫分析[J].遗传,2012,34(10):1271-1281.LI X L,YANG S B,TANG Z L,et al.Genome-wide selective sweep analysis on Large White and Tongcheng pigs[J].Hereditas (Beijing),2012,34(10):1271-1281.(in Chinese)
[14]	XU Z,SUN H,ZHANG Z,et al.Genome-wide detection of selective signatures in a Jinhua pig population[J].J Inter Agric, 2020,19(5):1314-1322.
[15]	CHEN W,FANG G F,WANG S D,et al.Longissimus lumborum muscle transcriptome analysis of Laiwu and Yorkshire pigs differing in intramuscular fat content[J].Genes Genomics,2017,39(7):759-766.
[16]	WANG X P,ZHANG H,HUANG M,et al.Whole-genome SNP markers reveal conservation status,signatures of selection,and introgression in Chinese Laiwu pigs[J].Evol Appl,2021,14(2):383-398.
[17]	ZHANG W,YANG M,WANG Y L,et al.Genomic analysis reveals selection signatures of the Wannan Black pig during domestication and breeding[J].Asian-Australas J Anim Sci,2020,33(5):712-721.
[18]	XU P,WANG X P,NI L G,et al.Genome-wide genotyping uncovers genetic diversity,phylogeny,signatures of selection,and population structure of Chinese Jiangquhai pigs in a global perspective[J].J Anim Sci,2019,97(4):1491-1500.
[19]	WU F,SUN H,LU S X,et al.Genetic diversity and selection signatures within diannan small-ear pigs revealed by next-generation sequencing[J].Front Genet,2020,11:733.
[20]	GIBSON J,MORTON N E,COLLINS A.Extended tracts of homozygosity in outbred human populations[J].Hum Mol Genet,2006,15(5):789-795.
[21]	PERIPOLLI E,MUNARI D P,SILVA M V G B,et al.Runs of homozygosity:current knowledge and applications in livestock[J]. Anim Genet,2017,48(3):255-271.
[22]	CEBALLOS F C,JOSHI P K,CLARK D W,et al.Runs of homozygosity:windows into population history and trait architecture[J]. Nat Rev Genet,2018,19(4):220-234.
[23]	PEMBERTON T J,ABSHER D,FELDMAN M W,et al.Genomic patterns of homozygosity in worldwide human populations[J]. Am J Hum Genet,2012,91(2):275-292.
[24]	MASTRANGELO S,CIANI E,SARDINA M T,et al.Runs of homozygosity reveal genome-wide autozygosity in Italian sheep breeds[J].Anim Genet,2018,49(1):71-81.
[25]	HE S G,DI J,HAN B,et al.Genome-wide scan for runs of homozygosity identifies candidate genes related to economically important traits in Chinese Merino[J].Animals (Basel),2020,10(3):524.
[26]	NANDOLO W,UTSUNOMIYA Y T,MÉSZÁROS G,et al.Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances[J].Genet Sel Evol,2018,50(1):43.
[27]	ZHANG Z,ZHANG Q Q,XIAO Q,et al.Distribution of runs of homozygosity in Chinese and Western pig breeds evaluated by reduced-representation sequencing data[J].Anim Genet,2018,49(6):579-591.
[28]	WANG X P,ZHANG H,HUANG M,et al.Whole-genome SNP markers reveal conservation status,signatures of selection,and introgression in Chinese Laiwu pigs[J].Evol Appl,2021,14(2):383-398.
[29]	CHANG C C,CHOW C C,TELLIER L C,et al.Second-generation PLINK:rising to the challenge of larger and richer datasets[J].Gigascience,2015,4(1):7.
[30]	YANG J,LEE S H,GODDARD M E,et al.GCTA:a tool for genome-wide complex trait analysis[J].Am J Hum Genet,2011, 88(1):76-82.
[31]	PRICE A L,PATTERSON N J,PLENGE R M,et al.Principal components analysis corrects for stratification in genome-wide association studies[J].Nat Genet,2006,38(8):904-909.
[32]	R CORE Team.R:a language and environment for statistical computing[R].Vienna,Austria:R Core Team,2020.
[33]	VOIGHT B F,KUDARAVALLI S,WEN X Q,et al.A map of recent positive selection in the human genome[J].PLoS Biol,2006, 4(3):e72.
[34]	PICKRELL J K,COOP G,NOVEMBRE J,et al.Signals of recent positive selection in a worldwide sample of human populations[J].Genome Res,2009,19(5):826-837.
[35]	SCHEET P,STEPHENS M.A fast and flexible statistical model for large-scale population genotype data:applications to inferring missing genotypes and haplotypic phase[J].Am J Hum Genet,2006,78(4):629-644.
[36]	王光凯,曾滔,王慧华,等.苏尼特羊全基因组选择信号检测[J].中国农业科学,2014,47(6):1190-1199.WANG G K,ZENG T,WANG H H,et al.Genome-wide detection of selection signature on Sunite sheep[J].Scientia Agricultura Sinica,2014,47(6):1190-1199.(in Chinese)
[37]	HOWE K L,ACHUTHAN P,ALLEN J,et al.Ensembl 2021[J].Nucleic Acids Res,2021,49(D1):D884-D891.
[38]	HU Z L,PARK C A,REECY J M.Building a livestock genetic and genomic information knowledgebase through integrative developments of Animal QTLdb and CorrDB[J].Nucleic Acids Res,2019,47(D1):D701-D710.
[39]	《中国家畜家禽品种志》编委会.中国猪品种志[M].上海:上海科学技术出版社,1986.China National Commission of Livestock and Poultry Breeds Library.China pigs breeds library[M].Shanghai:Shanghai Scientific & Technical Publishers,1986.(in Chinese)
[40]	YANG Y,ADEOLA A C,XIE H B,et al.Genomic and transcriptomic analyses reveal selection of genes for puberty in Bama Xiang pigs[J].Zool Res,2018,39(6):424-430.
[41]	MUÑOZ G,OVILO C,ESTELLÉ J,et al.Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line[J].Genet Sel Evol,2007,39(2):195-206.
[42]	LU P F,EWALD A J,MARTIN G R,et al.Genetic mosaic analysis reveals FGF receptor 2 function in terminal end buds during mammary gland branching morphogenesis[J].Dev Biol,2008,321(1):77-87.
[43]	王亚楠.9个中外猪品种全基因组选择区域及拷贝数变异分析[D].武汉:华中农业大学,2015.WANG Y N.Genome-wide analysis of selective regions and copy number variations among nine chinese and western pig breeds[D].Wuhan:Huazhong Agricultural University,2015.(in Chinese)
[44]	郭丽丽.ADAMTS家族在肿瘤中的研究进展[J].医学综述,2015,21(11):1975-1979.GUO L L.Research progress of a disintegrin and metalloproteinase with thrombospondin family in tumor[J].Medical Recapitulate, 2015,21(11):1975-1979.(in Chinese)
[45]	姜志平,李风艳.单核细胞趋化蛋白-1及其受体与肿瘤侵袭转移的研究进展[J].肿瘤学杂志,2021,27(5):353-358.JIANG Z P,LI F Y.Research progress on monocyte chemoattractant protein-1 and its receptors in tumor invasion and metastasis[J].Journal of Chinese Oncology,2021,27(5):353-358.(in Chinese)
[46]	王乐旬,张盛昔,吴惠娟,等.巨噬细胞极化中特异性分子表达的实验研究[J].广东药科大学学报,2020,36(1):43-49.WANG L X,ZHANG S X,WU H J,et al.Experimental study on the expression of specific molecules in macrophage polarization[J]. Journal of Guangdong Pharmaceutical University,2020,36(1):43-49.(in Chinese)
[47]	ZHANG X,CHEN L,DANG W Q,et al.CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling[J].Lab Invest,2020,100(4):619-629.
[48]	LIN S H,ZHANG X C,HUANG G H,et al.Myeloid-derived suppressor cells promote lung cancer metastasis by CCL11 to activate ERK and AKT signaling and induce epithelial-mesenchymal transition in tumor cells[J].Oncogene,2021,40(8):1476-1489.