基于全基因组Fst和nSL分析鉴别苏淮猪中性洗涤纤维表观消化率相关候选基因位点

doi:10.11843/j.issn.0366-6964.2021.07.005

畜牧兽医学报 ›› 2021, Vol. 52 ›› Issue (7): 1809-1819.doi: 10.11843/j.issn.0366-6964.2021.07.005

基于全基因组Fst和nSL分析鉴别苏淮猪中性洗涤纤维表观消化率相关候选基因位点

李开军^1,2, 侯黎明^1,2, 蒲广^1,2, 刘航^1,2, 刘根盛^1,2, 石传宗^1,2, 金通², 周娟³, 李平华^1,2,4,5*, 黄瑞华^1,2,4*

1. 南京农业大学养猪研究所, 南京 210095;
2. 南京农业大学淮安研究院, 淮安 223001;
3. 淮安市淮阴新淮种猪场, 淮安 223322;
4. 江苏现代农业(生猪)产业技术体系集成创新中心, 南京 210095;
5. 淮安沐林新农村发展研究有限公司, 淮安 223001

收稿日期:2020-12-17 出版日期:2021-07-23 发布日期:2021-07-23
通讯作者: 李平华,主要从事猪健康生产学与遗传育种学研究,E-mail:lipinghua718@njau.edu.cn;黄瑞华,主要从事猪健康生产学与遗传育种学研究,E-mail:rhhuang@njau.edu.cn
作者简介:李开军(1995-),男,江苏盐城人,硕士生,主要从事猪肠道健康与耐粗饲机制研究,E-mail:2018105008@njau.edu.cn
基金资助:
国家自然科学基金（31872318）；江苏现代农业产业技术体系建设专项资金（JATS[2020]399；JATS[2020]179）

Identification of Candidate Gene Loci Related to Apparent NDF Digestibility of Suhuai Pigs Based on Genome-wide Fst and nSL Analyses

LI Kaijun^1,2, HOU Liming^1,2, PU Guang^1,2, LIU Hang^1,2, LIU Gensheng^1,2, SHI Chuanzong^1,2, JIN Tong², ZHOU Juan³, LI Pinghua^1,2,4,5*, HUANG Ruihua^1,2,4*

1. Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China;
2. Huai'an Academy, Nanjing Agricultural University, Huai'an 223001, China;
3. Huaiyin Xinhuai Pig Breeding Farm of Huai'an City, Huai'an 223322, China;
4. Industrial Technology System Integration Innovation Center of Jiangsu Modern Agriculture (PIG), Nanjing 210095, China;
5. Mulin New Rural Research and Development Corporation of Huai'an City, Huai'an 223001, China

Received:2020-12-17 Online:2021-07-23 Published:2021-07-23

摘要/Abstract

摘要： 旨在鉴定苏淮猪（含25%淮猪和75%大白猪血统的国家级新品种）在培育过程中受选择的与纤维表观消化率性状相关的基因片段，为解析苏淮猪耐粗饲遗传机制奠定基础。本研究首先检测分析了331头160日龄苏淮猪个体的中性洗涤纤维（neutral detergent fiber，NDF）表观消化率，计算群体NDF表观消化率估计育种值（estimated breeding value，EBV），选择其中EBV极高和极低各10%的个体（N=66）进行猪80K芯片基因分型。借助群体分化指数（fixation index，Fst）和按长度划分隔离点数（number of segregating sites by length，nSL）法分析苏淮猪群体内的选择信号分布情况，寻找选择信号区域内与纤维消化相关的重要基因。最后，选择两种分析中受选择的共有SNPs位点在苏淮猪全群分型，开展与NDF表观消化率的关联性分析，进一步确定影响苏淮猪NDF表观消化率的SNPs位点。结果显示，通过对高、低NDF表观消化率苏淮猪群体芯片分型数据质控，共有51 367个有效SNPs位点用于后续分析。通过Fst和nSL选择信号分析，共鉴定到146个受选择信号区域和361个受选择的基因，其中多个基因被报道与肠道健康和肠道发育等功能相关，包括MTHFD1L、PHLPP1、TRPM6、MCC、NEDD9、UVRAG和KLF5等基因。选择两种分析中受选择且共有的8个SNPs位点，通过SNP与苏淮猪全群NDF表观消化率的关联性分析，发现rs81363074、rs327393763和rs81404927位点与苏淮猪群体NDF表观消化率存在显著关联（P<0.05），rs81347101和rs318870857位点与苏淮猪群体NDF表观消化率存在极显著关联（P<0.01）。其中，rs81363074位点位于MCC基因第二内含子上。通过高、低NDF表观消化率苏淮猪群体Fst和nSL选择信号分析，筛选到146个受选择信号区域，鉴定到影响苏淮猪NDF表观消化率的受选择候选基因MTHFD1L、PHLPP1、TRPM6、MCC、NEDD9、UVRAG和KLF5，筛选到了5个与NDF表观消化率显著关联的SNPs位点。本研究结果为解析苏淮猪耐粗饲性状的遗传机制奠定了重要基础。

关键词: 苏淮猪, 纤维表观消化率, 选择信号, Fst, nSL, 纤维消化相关基因

Abstract: This study aimed to identify the selected gene regions related to the apparent NDF digestibility during the breeding process of Suhuai pigs (a national new breed containing 25% Huai pig lineage and 75% Large White pig lineage) and provide an important foundation for analyzing the genetic mechanism of crude fiber tolerance in Suhuai pigs. Firstly, the apparent digestibility of neutral detergent fiber (NDF) of 331 160-day-old Suhuai pigs were measured. The estimated breeding value (EBV) of apparent NDF digestibility in Suhuai pigs were calculated. Suhuai pigs with extremely high 10% (n=33) and extremely low 10% (n=33) of EBV_NDF were selected to perform 80K chip genotyping. The fixation index (Fst) and the number of segregating sites by length (nSL) methods were adopted to analyze the selection signals distribution in Suhuai pig populations, and to detect the candidate genes related to fiber digestion located in selected signal regions. Finally, the common SNPs of selected sites in the Fst and nSL analyses were selected to genotype in the whole group of Suhuai pigs, and then the association analysis between SNPs and apparent NDF digestibility was carried out to further determine the candidate SNPs related to the apparent NDF digestibility in Suhuai pigs. A total of 51 367 effective SNPs sites were used for the further analysis through the quality control of chip data of Suhuai pig populations with high and low apparent NDF digestibility. Furthermore, 146 selected signals regions and 361 selected genes were identified via Fst and nSL selection signals analysis. Among them, many genes had been reported to be related to intestinal health and intestinal development, including MTHFD1L, PHLPP1, TRPM6, MCC, NEDD9, UVRAG and KLF5. Only 8 common SNPs sites were identified in the two analyses. Association analysis results of SNPs with apparent NDF digestibility showed that rs81363074, rs327393763, and rs81404927 were significantly associated with apparent NDF digestibility (P<0.05), and the rs81347101 and rs318870857 were extremely significantly associated with the apparent NDF digestibility in Suhuai pig populations (P<0.01). Among them, the rs81363074 was located on the second intron of the MCC gene. One hundred and forty-six selected signals regions were identified based on the methods of Fst and nSL selection signals in Suhuai pigs with high and low apparent NDF digestibility. The selected candidate genes MTHFD1L, PHLPP1, TRPM6, MCC, NEDD9, UVRAG and KLF5 were identified to affect the apparent NDF digestibility in Suhuai pigs. Besides, 5 SNPs sites were significantly related to the apparent NDF digestibility. This results of this study provided an important foundation for analyzing the genetic mechanism of fiber tolerance trait in Suhuai pigs.

Key words: Suhuai pigs, apparent fiber digestibility, selection signals, Fst, nSL, genes related to fiber digestibility

中图分类号:

S828.2

李开军, 侯黎明, 蒲广, 刘航, 刘根盛, 石传宗, 金通, 周娟, 李平华, 黄瑞华. 基于全基因组Fst和nSL分析鉴别苏淮猪中性洗涤纤维表观消化率相关候选基因位点[J]. 畜牧兽医学报, 2021, 52(7): 1809-1819.

LI Kaijun, HOU Liming, PU Guang, LIU Hang, LIU Gensheng, SHI Chuanzong, JIN Tong, ZHOU Juan, LI Pinghua, HUANG Ruihua. Identification of Candidate Gene Loci Related to Apparent NDF Digestibility of Suhuai Pigs Based on Genome-wide Fst and nSL Analyses[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(7): 1809-1819.

参考文献 44

[1]	吴秋珏,徐廷生.饲粮中中性洗涤纤维的研究进展[J].饲料工业,2006,27(7):14-16.WU Q J,XU T S.Research progress of neutral detergent fiber in diet[J].Feed Industry,2006,27(7):14-16.(in Chinese)
[2]	张叶秋,郝帅帅,高硕,等.米糠高纤维日粮对苏淮猪生长性能及肠道功能的影响[J].南京农业大学学报,2016,39(5):807-813.ZHANG Y Q,HAO S S,GAO S,et al.Effects of rice bran source high fibre diet on growth performance and intestine function of Suhuai pigs[J].Journal of Nanjing Agricultural University,2016,39(5):807-813.(in Chinese)
[3]	郝帅帅,张叶秋,马翔,等.米糠替代部分玉米的高纤维日粮对苏淮母猪健康及脂肪相关指标的影响[J].畜牧与兽医,2016,48(5):18-25.HAO S S,ZHANG Y Q,MA X,et al.Effect of rice bran partially replacement of corn in diets on health and fatty acid metabolism in Suhuai pigs[J].Animal Husbandry & Veterinary Medicine,2016,48(5):18-25.(in Chinese)
[4]	蒲广,黄瑞华,牛清,等.日粮脱脂米糠替代玉米水平对苏淮猪生长性能、肠道发育及养分消化率的影响[J].畜牧兽医学报, 2019,50(4):758-770.PU G,HUANG R H,NIU Q,et al.Effects of dietary defatted rice bran substitute corn levels on growth performance,intestinal development and apparent digestibility of nutrients of Suhuai Pigs[J].Acta Veterinaria et Zootechnica Sinica,2019,50(4):758-770.(in Chinese)
[5]	TAJIMA F.Statistical method for testing the neutral mutation hypothesis by DNA polymorphism[J].Genetics, 1989,123(3):585-595.
[6]	NIELSEN R,WILLIAMSON S,KIM Y,et al.Genomic scans for selective sweeps using SNP data[J].Genome Res,2005, 15(11):1566-1575.
[7]	SABETI P C,REICH D E,HIGGINS J M,et al.Detecting recent positive selection in the human genome from haplotype structure[J].Nature,2002,419(6909):832-837.
[8]	FERRER-ADMETLLA A,LIANG M,KORNELIUSSEN T,et al.On detecting incomplete soft or hard selective sweeps using haplotype structure[J].Mol Biol Evol,2014,31(5):1275-1291.
[9]	WRIGHT S.The genetical structure of populations[J].Ann Eugen,1951,15(4):323-354.
[10]	张威.基于重测序揭示猪基因组中的选择信号[D].合肥:安徽农业大学,2019.ZHANG W.Re-sequencing analysis reveals the selection signature of the pig genome[D].Hefei:Anhui Agricultural University,2019.(in Chinese)
[11]	EICHSTAEDT C A,PAGANI L,ANTAO T,et al.Evidence of early-stage selection on EPAS1 and GPR126 genes in Andean high altitude populations[J].Sci Rep,2017,7(1):13042.
[12]	VATSIOU A I,BAZIN E,GAGGIOTTI O E.Detection of selective sweeps in structured populations:a comparison of recent methods[J].Mol Ecol,2016,25(1):89-103.
[13]	NIU Q,LI P H,HAO S S,et al.Characteristics of gut microbiota in sows and their relationship with apparent nutrient digestibility[J].Int J Mol Sci,2019,20(4):870.
[14]	PU G,LI P H,DU T R,et al.Adding appropriate fiber in diet increases diversity and metabolic capacity of distal gut microbiota without altering fiber digestibility and growth rate of finishing pig[J].Front Microbiol,2020,11:533.
[15]	MADSEN P,JENSEN J,LABOURIAU R,et al.DMU-a package for analyzing multivariate mixed models in quantitative genetics and genomics[C]//Proceedings of the 10th World Congress of Genetics Applied to Livestock Production.2014:18-22.
[16]	PURCELL S,NEALE B,TODD-BROWN K,et al.PLINK:A tool set for whole-genome association and population-based linkage analyses[J].Am J Hum Genet,2007,81(3):559-575.
[17]	BROWNING B L,BROWNING S R.Genotype imputation with millions of reference samples[J].Am J Hum Genet,2016,98(1):116-126.
[18]	WEIR B S,COCKERHAM C C.Estimating F-statistics for the analysis of population structure[J].Evolution, 1984, 38(6):1358-1370.
[19]	DANECEK P,AUTON A,ABECASIS G,et al.The variant call format and VCFtools[J].Bioinformatics,2011,27(15):2156-2158.
[20]	TURNER S D.Qqman:an R package for visualizing GWAS results using Q-Q and manhattan plots[J].J Open Sour Soft,2018, 3(25):731.
[21]	QANBARI S,PAUSCH H,JANSEN S,et al.Classic selective sweeps revealed by massive sequencing in cattle[J].PLoS Genet,2014,10(2):e1004148.
[22]	SZPIECH Z A,HERNANDEZ R D.Selscan:an efficient multithreaded program to perform EHH-based scans for positive selection[J].Mol Biol Evol,2014,31(10):2824-2827.
[23]	王振.太湖流域地方品种猪基因组结构及其功能研究[D].上海:上海交通大学,2015.WANG Z.Study on genomic architecture and function of Taihu pig breeds[D].Shanghai:Shanghai Jiao Tong University,2015.(in Chinese)
[24]	STELZER G,ROSEN N,PLASCHKES I,et al.The GeneCards Suite:from gene data mining to disease genome sequence analyses[J].Curr Protoc Bioinformatics,2016,54(1):1.30.1-1.30.33.
[25]	XIE C,MAO X Z,HUANG J J,et al.KOBAS 2.0:a web server for annotation and identification of enriched pathways and diseases[J].Nucleic Acids Res,2011,39(S2):W316-W322.
[26]	AGARWAL S,BEHRING M,HALE K,et al.MTHFD1L,a folate cycle enzyme,is involved in progression of colorectal cancer[J].Transl Oncol,2019,12(11):1461-1467.
[27]	LI X,STEVENS P D,LIU J Y,et al.PHLPP is a negative regulator of RAF1,which reduces colorectal cancer cell motility and prevents tumor progression in mice[J].Gastroenterology,2014,146(5):1301-1312.
[28]	LUONGO F,PIETROPAOLO G,GAUTIER M,et al.TRPM6 is essential for magnesium uptake and epithelial cell function in the colon[J].Nutrients,2018,10(6):784.
[29]	BENTHANI F A,HERRMANN D,TRAN P N,et al.‘MCC’ protein interacts with E-cadherin and β-catenin strengthening cell-cell adhesion of HCT116 colon cancer cells[J].Oncogene,2018,37(5):663-672.
[30]	HAN R,SUN Q,WU J,et al.Sodium butyrate upregulates miR-203 expression to exert anti-proliferation effect on colorectal cancer cells[J].Cell Physiol Biochem,2016,39(5):1919-1929.
[31]	QUACH C,SONG Y,GUO H R,et al.A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice[J].Nature Commun,2019,10(1):5681.
[32]	NANDAN M O,GHALEB A M,LIU Y,et al.Inducible intestine-specific deletion of Kruppel-like factor 5 is characterized by a regenerative response in adult mouse colon[J].Dev Biol,2014,387(2):191-202.
[33]	谭碧娥,伍树松,贺建华,等.地方猪耐粗饲和肉质性状形成的微生物代谢机制[J].动物营养学报,2020,32(7):2941-2946.TAN B E,WU S S,HE J H,et al.Metabolic mechanism of coarse feeding tolerance and meat quality traits formation based on microbial metabolism in local pigs[J].Chinese Journal of Animal Nutrition,2020,32(7):2941-2946.(in Chinese)
[34]	周根来,倪黎纲,张伟,等.生长肥育阶段姜曲海猪饲粮中适宜粗纤维水平的研究[J].家畜生态学报,2020,41(5):23-29.ZHOU G L,NI L G,ZHANG W,et al.Study on the appropriate crude fiber level in the diet of Jiangquhai pig in the growth and finishing stage[J].Acta Ecologae Animalis Domastici,2020,41(5):23-29.(in Chinese)
[35]	霍贵成.地方猪种对纤维饲料利用的研究——Ⅱ.消化道形态与大肠内容物重量的变化[J].畜牧兽医学报,1992,23(1):34-38.HUO G C.Local pig breeds for fiber feed utilization research——Ⅱ.Gastrointestinal forms and contents of the weight of large intestine[J].Acta Veterinaria et Zootechnica Sinica,1992,23(1):34-38.(in Chinese)
[36]	付金剑,李梦玥,胡音,等.日粮纤维水平对二花脸猪大肠肠道细胞增殖与凋亡基因表达和黏膜菌群数量的影响[J].畜牧与兽医,2020,52(10):24-28.FU J J,LI M Y,HU Y,et al.Effects of dietary fiber levels on the expression of apoptosis and proliferation genes in large intestinal cell and on mucosal bacteria of Erhualian pigs[J].Animal Husbandry & Veterinary Medicine,2020,52(10):24-28.(in Chinese)
[37]	杨岸奇,陈斌,冉茂良,等.基因组选择在猪杂交育种中的应用[J].遗传,2020,42(2):145-152.YANG A Q,CHEN B,RAN M L,et al.The application of genomic selection in pig cross breeding[J].Hereditas,2020,42(2):145-152.(in Chinese)
[38]	田明,冯艳忠,王文涛,等.种猪育种关键技术研究进展[J].猪业科学,2020,37(10):42-43.TIAN M,FENG Y Z,WANG W T,et al.Advances in research on key breeding techniques of swine[J].Swine Industry Science,2020,37(10):42-43.(in Chinese)
[39]	GUO T,YIN R X,YAO L M,et al.Integrative mutation,haplotype and G×G interaction evidence connects ABGL4,LRP8 and PCSK9 genes to cardiometabolic risk[J].Sci Rep,2016,6(1):37375.
[40]	INAGAKI Y,KASHIMA T G,HOOKWAY E S,et al.Dentine matrix protein 1(DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours[J].Virchows Arch,2015,466(4):445-452.
[41]	LEE J W,HONG J,SEYMEN F,et al.Novel frameshift mutations in DSPP cause dentin dysplasia type II[J].Oral Dis,2019,25(8):2044-2046.
[42]	LLOYD-BURTON S,ROSKAMS A J.SPARC-like 1(SC1) is a diversely expressed and developmentally regulated matricellular protein that does not compensate for the absence of SPARC in the CNS[J].J Comp Neurol,2012,520(12):2575-2590.
[43]	ROHANIZADEGAN M,SACHAROW S.Desmosterolosis presenting with multiple congenital anomalies[J].Eur J Med Genet, 2018, 61(3):152-156.
[44]	MAEKAWA M,YAMAGUCHI K,NAKAMURA T,et al.Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1[J].Nature,2011,474(7350):225-229.

基于全基因组Fst和nSL分析鉴别苏淮猪中性洗涤纤维表观消化率相关候选基因位点

Identification of Candidate Gene Loci Related to Apparent NDF Digestibility of Suhuai Pigs Based on Genome-wide Fst and nSL Analyses

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[13]	蒲广, 黄瑞华, 牛清, 王欢, 范丽娟, 高琛, 牛培培, 张总平, 吴承武, 周娟, 李平华. 日粮脱脂米糠替代玉米水平对苏淮猪生长性能、肠道发育及养分消化率的影响[J]. 畜牧兽医学报, 2019, 50(4): 758-770.
[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]	薛周舣源, 宋显威, 吴林慧, 王露珍, 崔家安, 孙章健, 张政, 马云龙. 畜禽选择信号检测方法及其统计学问题[J]. 畜牧兽医学报, 2018, 49(6): 1099-1107.