不同尾型绵羊全基因组选择信号检测

doi:10.11843/j.issn.0366-6964.2015.10.004

摘要/Abstract

摘要：

为研究不同尾型绵羊群体遗传分化程度，检测全基因组选择信号，以挖掘不同尾型绵羊重要性状相关的候选基因。本研究基于蒙古羊（短脂尾）和藏羊（瘦尾）群体的Illumina Ovine SNP 50K芯片分型数据，借助遗传分化系数F_ST法进行群体间选择信号检测，寻找选择信号区域内的重要基因，并对其中与脂肪代谢相关的基因PPARG、PDGFD在呼伦贝尔羊（大尾和小尾品系；肥尾）与藏羊（瘦尾）尾脂进行mRNA相对表达量研究。结果，（1）465个SNPs被选择，基因注释找到448个候选基因，筛选到50个与脂类代谢相关的基因，GO功能富集分析发现，主要富集在脂类生物合成过程、磷脂代谢、脂质结合等条目，此外发现4个基因（PPARG、RXRG、SLC27A2和ACSL6）富集到PPAR信号通路。（2）肥瘦尾之间，呼伦贝尔羊（大尾和小尾品系）PPARG和PDGFD基因表达量均显著高于藏羊（P<0.01），而大小肥尾之间，呼伦贝尔羊大尾品系PPARG基因表达量显著高于小尾品系（P<0.05），PDGFD基因表达量则无明显差异。通过FST法有效检测到受选择的基因，部分与绵羊重要性状相关，相对定量试验证明PPARG和PDGFD基因与尾部脂肪沉积密切相关，可以作为尾型选育的候选基因，为绵羊育种及改良提供重要参考。

关键词: 全基因组, 选择信号, 候选基因, 脂肪沉积, 群体分化指数（F_ST）

Abstract:

This experiment was conducted to study genetic differentiation between 2 sheep populations with distinct tail types by genome-wide detection of selection signatures and to search the candidate genes related to important traits of sheep.Based on the Illumina Ovine SNP 50K Breadchip genotyping data of Mongolian sheep and Tibetan sheep，population differentiation index FST was adopted to detect the selection signatures，and to found the genes located in selection signature regions.Based on the tail adipose tissue of Hulun Buir sheep(fat-tailed sheep，include large fat-tailed sheep and small fat-tailed sheep) and Tibetan sheep(thin-tailed sheep)，the relative expression study was adopted to explore the difference of gene relative expression level of PPARG and PDGFD，which were related to fat metabolism.This result showed that：(1) 465 selected SNPs were found，448 candidate genes were detected by gene annotation． And 50 genes related to lipid metabolism were selected from these candidate genes，the analysis of GO showed that these genes were related to lipid biosynthetic process，phospholipid metabolic process and lipid binding.In addition，4 genes were found，PPARG，RXRG，SLC27A2 and ACSL6，and enriched into the PPAR signaling pathway.(2)The gene relative expression levels of PPARG and PDGFD from Hulun Buir sheep was significantly higher than that of Tibetan sheep(P<0.01)， between fat-tailed and thin-tailed sheep，the gene relative expression level of PPARG from lager fat-tailed Hulun Buir sheep was significantly higher than that of small fat-tailed Hulun Buir sheep(P<0.05)，but the gene relative expression level of PDGFD had no significant difference between lager fat-tailed and small fat-tailed Hulun Buir sheep.F_ST could be used to detect the genes with selection signatures and some of the candidate genes were related to important traits in sheep.PPARG and PDGFD genes were proved to be closely related to tail fat deposition through the relative expression studies，these genes could be used as candidate genes for different tailed sheep breeding.This study can provide theoretical references for sheep breeding or breed improvement.

Key words: whole genome, selection signatures, candidate gene, fat deposition, population differentiation index F_ST

中图分类号:

S826.2

刘真，王慧华，刘瑞凿，吴明明，张淑珍，张莉，赵福平，杜立新，魏彩虹. 不同尾型绵羊全基因组选择信号检测[J]. 畜牧兽医学报, 2015, 46(10): 1721-1732.

LIU Zhen，WANG Hui-hua，LIU Rui-zao，WU Ming-ming，ZHANG Shu-zhen，ZHANG Li，ZHAO Fu-ping，DU Li-xin，WEI Cai-hong. Genome-wide Detection of Selection Signatures of Distinct Tail Types in Sheep Populations[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(10): 1721-1732.

参考文献

［1］CHESSA B，PEREIRA F，ARNAUD F，et al.Revealing the history of sheep domestication using retrovirus integrations［J］.Science，2009，324(5926)：532-536.
［2］国家畜禽遗传资源委员会.中国畜禽遗传资源志•羊志［M］.北京：中国农业出版社，2011.
China National Commission of Animal Genetic Resources.Animal Genetic Resources in China.Sheep and Goat［M］.Beijing：Chinese Agricultural Press，2011.(in Chinese)
［3］MEGENS H J，CROOIJMANS R P，SAN CRISTOBAL M，et al.Biodiversity of pig breeds from China and Europe estimated from pooled DNA samples：differences in microsatellite variation between two areas of domestication［J］. GSE，2008，40(1)：103-128.
［4］马云龙，张勤，丁向东.利用高密度SNP检测不同猪品种间X染色体选择信号［J］.遗传，2012，34(10)：33-42.
MA Y L，ZHANG Q，DING X D，et al.Detecting selection signatures on X chromosome in pig through high density SNPs［J］.Hereditas，2012，34(10)：33-42.(in Chinese)
［5］许忠能.生物信息学［M］.北京：清华大学出版社，2008.
XU Z N.Bioinformatics［M］.Beijing：Tsinghua University Press，2008.(in Chinese)
［6］THORNTON K R，JENSEN J D.Controlling the false-positive rate in multilocus genome scans for selection［J］.Genetics，2007，175(2)：737-750.
［7］AKEY J M，ZHANG G，ZHANG K，et al.Interrogating a high-density SNP map for signatures of natural selection［J］.Genome Res，2002，12(12)：1805-1814.
［8］AMARAL A J，FERRETTI L，MEGENS H J，et al.Genome-wide footprints of pig domestication and selection revealed through massive parallel sequencing of pooled DNA［J］.PLoS ONE，2011，6(4)：e14782.
［9］FLORI L，FRITZ S，JAFFREZIC F，et al.The genome response to artificial selection：a case study in dairy cattle［J］.PLoS ONE，2009，4(8)：e6595.
［10］GU J，ORR N，PARK S D，et al.A genome scan for positive selection in thoroughbred horses［J］.PLoS ONE，2009，4(6)：e5767.
［11］KARLSSON E K，BARANOWSKA I，WADE C M，et al.Efficient mapping of mendelian traits in dogs through genome-wide association［J］.Nat Genet，2007，39(11)：1321-1328.
［12］KIJAS J W，LENSTRA J A，HAYES B，et al.Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection［J］.PLoS Biol，2012，10(2)：e1001258.
［13］PARISET L，JOOST S，MARSAN P A，et al.Landscape genomics and biased F_ST approaches reveal single nucleotide polymorphisms under selection in goat breeds of North-East Mediterranean［J］.BMC Genet，2009，10：7.
［14］MORADI M H，NEJATI-JAVAREMI A，MORADI-SHAHRBABAK M，et al.Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition［J］.BMC Genet，2012，13：10.
［15］甘尚权，张伟，沈敏，等.绵羊X染色体59383635位点多态性与脂尾性状的相关性分析［J］.遗传，2013，35(10)：1209-1216.
GAN S Q，ZHANG W，SHEN M，et al.Correlation analysis between polymorphism of the 59383635th locus on X chromosome and fat-tail trait in sheep［J］. Hereditas，2013，35(10)：1209-1216.(in Chinese)
［16］WEIR B S，HILL W G.Estimating F-statistics［J］.Ann Rev Genet，2002，36：721-750.
［17］HUA X，WU J，GOLDSTEIN J L，et al.Structure of the human gene encoding sterol regulatory element binding protein-1(SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13［J］.Genomics，1995，25(3)：667-673.
［18］TONTONOZ P，HU E，SPIEGELMAN B M.Stimulation of adipogenesis in fibroblasts by PPAR gamma 2，a lipid-activated transcription factor［J］.Cell，1994，79(7)：1147-1156.
［19］TONTONOZ P，KIM J，GRAVES R，et al.ADD1：a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation［J］.Mol Cell Biol，1993，13(8)：4753-4759.
［20］ARTEMENKO Y，GAGNON A，AUBIN D，et al.Anti-adipogenic effect of PDGF is reversed by PKC inhibition［J］.J Cell Physiol，2005，204(2)：646-653.
［21］HOLMSTRÖM T E，MATTSSON C L，FÄLTING J M，et al.Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes［J］.Exp Cell Res，2008，314(19)：3581-3592.
［22］LAROCHELLE W J，JEFFERS M，MCDONALD W F，et al.PDGF-D，a new protease-activated growth factor［J］.Nat Cell Biol，2001，3(5)：517-521.
［23］LEWONTIN R C，KRAKAUER J.Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms［J］.Genetics(Print)，1973，74(1)：175-195.
［24］CAVALLI-SFORZA L L.Population structure and human evolution［J］.Proc Royal Soc London.Series B：Biol Sci，1966，164：362-379.
［25］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)：53-63.
LI X L，YANG S B，TANG Z L，et al.Genome-wide selective sweep analysis on Large White and Tongcheng pigs［J］.Hereditas，2012，34(10)：53-63.(in Chinese)
［26］刘喜冬，王志鹏，樊惠中，等.基于高密度SNP标记的肉牛人工选择痕迹筛查［J］.遗传，2012，34(10)：86-95.
LIU X D，WANG Z P，FAN H Z，et al.Artificial selection for cattle based on high-density SNP markers［J］.Hereditas，2012，34(10)：86-95.(in Chinese)
［27］曾滔，赵福平，王光凯，等.基于群体分化指数F_ST的绵羊全基因组选择信号检测［J］.畜牧兽医学报，2013，44(12)：1891-1899.
ZENG T，ZHAO F P，WANG G K，et al.Genome-wide detection of selection signatures in sheep populations with use of population differentiation index F_ST［J］.Acta Veterinaria Et Zootechnica Sinica，2013，44(12)：1891-1899.(in Chinese)
［28］ZHANG M，SU Y Q，SUGIURA K，et al.Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2(NPR2) and meiotic arrest in mouse oocytes in vitro［J］.Endocrinology，2011，152(11)：4377-4385.
［29］DOYLE L A，YANG W，ABRUZZO L V，et al.A multidrug resistance transporter from human MCF-7 breast cancer cells［J］.Proc Natl Acad Scie USA，1998，95(26)：15665-15670.
［30］OLSEN H G，NILSEN H，HAYES B，et al.Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle［J］.BMC Genet，2007，8：32.
［31］YANG F C，INGRAM D A，CHEN S，et al.Nf1-dependent tumors require a microenvironment containing Nf1+/--and c-kit-dependent bone marrow［J］.Cell，2008，135(3)：437-448.
［32］PALMIERI C，ROBERTS-CLARK D，ASSADI-SABET A，et al.Fibroblast growth factor 7，secreted by breast fibroblasts，is an interleukin-1beta-induced paracrine growth factor for human breast cells［J］. J Endocrinol，2003，177(1)：65-81.
［33］QANBARI S，GIANOLA D，HAYES B，et al.Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle［J］.BMC Genomics，2011，12(1)：318.
［34］BEVITT D J，LI Z，LINDROP J L，et al.Analysis of full length ADAMTS6 transcript reveals alternative splicing and a role for the 5′ untranslated region in translational control［J］.Gene，2005，359：99-110.
［35］LI R，TANG X L，MIAO S Y，et al.Regulation of the G2/M phase of the cell cycle by sperm associated antigen 8(SPAG8) protein［J］.Cell Biochem Function，2009，27(5)：264-268.
［36］MARTIN J，MAURHOFER O，BELLANCE N，et al.Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function［J］.Hepatology，2013，57(5)：2037-2048.
［37］ZHANG L，LIU J，ZHAO F，et al.Genome-wide association studies for growth and meat production traits in sheep［J］.PLoS ONE，2013，8(6)：e66569.
［38］NEWGARD C B，BRADY M J，O′DOHERTY R M，et al.Organizing glucose disposal：emerging roles of the glycogen targeting subunits of protein phosphatase-1［J］.Diabetes，2000，49(12)：1967-1977.
［39］NIKOLA A，SERENA Z，LORENA Z，et al.Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo［J］.Mol Therapy，2004，10(5)：844-854.
［40］COMERFORD K M，LEONARD M O，CUMMINS E P，et al.Regulation of protein phosphatase 1gamma activity in hypoxia through increased interaction with NIPP1：implications for cellular metabolism［J］.J Cell Physiol，2006，209(1)：211-218.
［41］AN W，GUNTHER D M，WIM H，et al.Identification and prioritization of NUAK1 and PPP1CC as positional candidate loci for skeletal muscle strength phenotypes［J］.Physiol Genomics(Online)，2011，43(17)：981.
［42］WIRTANEN L，SÉGUIN C.Cloning of cDNAs encoding retinoic acid receptors RARγ1，RARγ2，and a new splicing variant，RARγ3，from Ambystoma mexicanum and characterization of their expression during early development［J］.BBA-Gene Struct Exp，2000，1492(1)：97-101.
［43］黄萌，许尚忠，昝林森，等.牛RXRG基因遗传变异与双胎性状的关联分析［J］.遗传，2008，30(2)：190-194.
HUANG M，XU S Z，ZAN L S，et al.Genetic variation in RXRG gene and its relationship with twinning trait in cattle［J］. Hereditas，2008，30(2)：190-194.(in Chinese)
［44］ARMAN E，HAFFNER-KRAUSZ R，CHEN Y，et al.Targeted disruption of fibroblast growth factor(FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development［J］.Proc Natl Acad Sci，1998，95(9)：5082-5087.
［45］MICHAEL D D，ALVAREZ I M，OCON O M，et al.Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm［J］.Endocrinology，2006，147(7)：3571-3579.
［46］LEE S H，SCHLOSS D J，SWAIN J L.Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor［J］.J Biol Chem，2000，275(43)：33679-33687.
［47］AHMED Z M，YOUSAF R，LEE B C，et al.Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74［J］.Am J Hum Genet，2011，88(1)：19-29.
［48］BOYKO A R，QUIGNON P，LI L，et al.A simple genetic architecture underlies morphological variation in dogs［J］.PLoS Biol，2010，8(8)：e1000451.
［49］VAYSSE A，RATNAKUMAR A，DERRIEN T，et al.Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping［J］.PLoS Genet，2011，7(10)：e1002316.
［50］JOHNSTON S E，MCEWAN J，PICKERING N K，et al.Genome-wide association mapping identifies the genetic basis of discrete and quantitative variation in sexual weaponry in a wild sheep population［J］.Mol Ecol，2011，20(12)：2555-2566.
［51］GAUTIER M，NAVES M.Footprints of selection in the ancestral admixture of a New World Creole cattle breed［J］.Mol Ecol，2011，20(15)：3128-3143.
［52］HAYES B J，PRYCE J，CHAMBERLAIN A J，et al.Genetic architecture of complex traits and accuracy of genomic prediction：coat colour，milk-fat percentage，and type in Holstein cattle as contrasting model traits［J］.PLoS Genet，2010，6(9)：e1001139.
［53］ANTONIADES H N.Human platelet-derived growth factor(PDGF)：purification of PDGF-I and PDGF-II and separation of their reduced subunits［J］.Proc Natl Acad Sci，1981，78(12)：7314-7317.
［54］ROSS R，GLOMSET J，KARIYA B，et al.A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro［J］. Proc Natl Acad Sci，1974，71(4)：1207-1210.
［55］TONTONOZ P，SPIEGELMAN B M.Fat and beyond：the diverse biology of PPARγ［J］.Annu Rev Biochem，2008，77：289-312.
［56］JONES J R，BARRICK C，KIM K A，et al.Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance［J］. Proc Natl Acad Sci USA，2005，102(17)：1107-1115.
［57］OKUNO A，TAMEMOTO H，TOBE K，et al.Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats［J］.J Clin Invest，1998，101(6)：1354.
［58］PETERS J M，HENNUYER N，STAELS B，et al.Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor α-deficient mice［J］.J Biol Chem，1997，272(43)：27307-27312.
［59］DESVERGNE B，WAHLI W.Peroxisome proliferator-activated receptors：nuclear control of metabolism 1［J］.Endocrine Rev，1999，20(5)：649-688.
［60］YANG W L，FRUCHT H.Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells［J］.Carcinogenesis，2001，22(9)：1379-1383.
［61］林婄婄，高中元，袁亚男，等.PPARα和PPARγ基因在不同脂尾型绵羊脂肪组织中的发育性表达研究［J］.畜牧兽医学报，2012，43(9)：1369-1376.
LIN P P，GAO Z Y，YUAN Y N，et al.Developmental expression of PPARα and PPARγ mRNA in adipose tissues of different fat-tailed sheep［J］.Acta Veterinaria Et Zootechnica Sinica，2012，43(9)：1369-1376.(in Chinese)

[1]	王璟, 滑留帅, 陈俊峰, 张家庆, 任巧玲, 白红杰, 郭红霞, 徐照学, 邢宝松, 白献晓, 曹海. 去势对淮南公猪背最长肌转录组的影响[J]. 畜牧兽医学报, 2019, 50(9): 1746-1758.
[2]	邓天宇, 樊红樱, 杜立新, 赵福平, 王立贤. 呼伦贝尔羊重要脂肪相关基因mRNA差异表达分析[J]. 畜牧兽医学报, 2019, 50(9): 1926-1935.
[3]	刘家鑫, 魏霞, 邓天宇, 谢锐, 韩建林, 杜立新, 赵福平, 王立贤. 绵羊全基因组ROH检测及候选基因鉴定[J]. 畜牧兽医学报, 2019, 50(8): 1554-1566.
[4]	牛凯, 程汝佳, 许冠龙, 冯宇, 孙石静, 范学政, 彭小薇, 朱良全, 秦玉明, 丁家波, 常维山, 蒋卉. 一株鹿源牛种布鲁菌的鉴定及全基因组分析[J]. 畜牧兽医学报, 2019, 50(8): 1666-1675.
[5]	刘家鑫, 魏霞, 邓天宇, 谢锐, 韩建林, 杜立新, 赵福平, 王立贤. 绵羊全基因组ROH检测及候选基因鉴定[J]. 畜牧兽医学报, 2019, 50(8): 1554-1566.
[6]	牛凯, 程汝佳, 许冠龙, 冯宇, 孙石静, 范学政, 彭小薇, 朱良全, 秦玉明, 丁家波, 常维山, 蒋卉. 一株鹿源牛种布鲁菌的鉴定及全基因组分析[J]. 畜牧兽医学报, 2019, 50(8): 1666-1675.
[7]	赵亚涵, 郝海生, 杜卫华, 庞云渭, 闫长亮, 刘岩, 赵善江, 赵学明, 朱化彬. 新鲜、玻璃化冷冻牛卵母细胞体外受精囊胚全基因组甲基化模式初探[J]. 畜牧兽医学报, 2019, 50(6): 1179-1188.
[8]	赵亚涵, 郝海生, 杜卫华, 庞云渭, 闫长亮, 刘岩, 赵善江, 赵学明, 朱化彬. 新鲜、玻璃化冷冻牛卵母细胞体外受精囊胚全基因组甲基化模式初探[J]. 畜牧兽医学报, 2019, 50(6): 1179-1188.
[9]	成志敏, 张宁芳, 王媛媛, 乐宝玉, 张万锋, 宋鹏康, 郭晓红, 高鹏飞, 蔡春波, 曹果清, 李步高. 基于RNA-Seq技术筛选影响猪肌纤维性状的候选基因[J]. 畜牧兽医学报, 2019, 50(5): 918-929.
[10]	成志敏, 张宁芳, 王媛媛, 乐宝玉, 张万锋, 宋鹏康, 郭晓红, 高鹏飞, 蔡春波, 曹果清, 李步高. 基于RNA-Seq技术筛选影响猪肌纤维性状的候选基因[J]. 畜牧兽医学报, 2019, 50(5): 918-929.
[11]	苑洪霞, 骆金红, 冯文武, 陈祥. 猪LYRM1基因对脂肪沉积的影响研究[J]. 畜牧兽医学报, 2019, 50(4): 677-687.
[12]	苑洪霞, 骆金红, 冯文武, 陈祥. 猪LYRM1基因对脂肪沉积的影响研究[J]. 畜牧兽医学报, 2019, 50(4): 677-687.
[13]	吴林慧, 孙琦, 王荔茹, 张凯丽, 谢胜松, 李新云, 赵书红, 马云龙. 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.
[14]	吴林慧, 孙琦, 王荔茹, 张凯丽, 谢胜松, 李新云, 赵书红, 马云龙. 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.
[15]	尹立林, 马云龙, 项韬, 朱猛进, 余梅, 李新云, 刘小磊, 赵书红. 全基因组选择模型研究进展及展望[J]. 畜牧兽医学报, 2019, 50(2): 233-242.