Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits

Liming Zhao; Lvfeng Yuan; Fadi Li; Xiaoxue Zhang; Huibin Tian; Zongwu Ma; Deyin Zhang; Yukun Zhang; Yuan Zhao; Kai Huang; Xiaolong Li; Jiangbo Cheng; Dan Xu; Xiaobin Yang; Kunchao Han; Xiuxiu Weng; Weimin Wang

doi:10.1016/j.jgg.2024.03.015

Volume 51 Issue 8

Aug. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2024 > 51(8): 866-876

PDF( 2347 KB)

Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits

doi: 10.1016/j.jgg.2024.03.015

a. State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, Gansu 730020, China;
b. Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, China;
c. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu 730070, China

Funds:

This work was supported by the National Key Research and Development Program of China (2021YFD1300901, 2022YFD1302000), and National Natural Science Foundation of China (32260818, 31960653).

Received Date: 2023-12-26
Accepted Date: 2024-03-30
Rev Recd Date: 2024-03-30

Available Online: 2025-06-06

Publish Date: 2024-04-04

Abstract

Abstract

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genomic selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35 (GPR35 g.952651 A>G; GPR35 g.952496 C>T) and NAV1 (NAV1 g.84216190 C>T; NAV1 g.84227412 G>A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.
- Hu sheep,
- Whole-genome resequencing,
- Selection signature,
- GPR35,
- NAV1,
- Single nucleotide polymorphism

FullText(HTML)

References(75)

References

Alexander, D., Novembre, J.,Lange, K., 2009. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 19, 1655-1664.

Axelsson, E., Ratnakumar, A., Arendt, M., Maqbool, K., Webster, M., Perloski, M., Liberg, O., Arnemo, J., Hedhammar, A.,Lindblad-Toh, K., 2013. The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature. 495, 360-364.

Cao, Y., Xu, S., Shen, M., Chen, Z., Gao, L., Lv, F., Xie, X., Wang, X., Yang, H., Liu, C., et al., 2021. Historical introgression from wild relatives enhanced climatic adaptation and resistance to pneumonia in sheep. Mol. Biol. Evol. 38, 838-855.

Chen, H., Patterson, N.,Reich, D., 2010. Population differentiation as a test for selective sweeps. Genome Res. 20, 393-402.

Chen, Z., Xu, Y., Xie, X., Wang, D., Aguilar-Gomez, D., Liu, G., Li, X., Esmailizadeh, A., Rezaei, V., Kantanen, J., et al., 2021. Whole-genome sequence analysis unveils different origins of european and asiatic mouflon and domestication-related genes in sheep. Commun. Biol. 4, 1307.

Chessa, B., Pereira, F., Arnaud, F., Amorim, A., Goyache, F., Mainland, I., Kao, R., Pemberton, J., Beraldi, D., Stear, M., et al., 2009. Revealing the history of sheep domestication using retrovirus integrations. Science. 324, 532-536.

Ciani, E., Mastrangelo, S., Da Silva, A., Marroni, F., Ferencakovic, M., Ajmone-Marsan, P., Baird, H., Barbato, M., Colli, L., Delvento, C., et al., 2020. On the origin of european sheep as revealed by the diversity of the balkan breeds and by optimizing population-genetic analysis tools. Genet. Sel. Evol. 52, 25.

Cingolani, P., Platts, A., Wang, L.L., Coon, M., Nguyen, T., Wang, L., Land, S.J., Lu, X.,Ruden, D.M., 2012. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly. 6, 80-92.

Danecek, P., Auton, A., Abecasis, G., Albers, C.A., Banks, E., DePristo, M.A., Handsaker, R.E., Lunter, G., Marth, G.T., Sherry, S.T., et al., 2011. The variant call format and VCFtools. Bioinformatics. 27, 2156-2158.

De Giovanni, M., Chen, H., Li, X.,Cyster, J., 2023. GPR35 and mediators from platelets and mast cells in neutrophil migration and inflammation. Immunol. Rev. 317, 187-202.

de Simoni Gouveia, J., da Silva, M., Paiva, S.,de Oliveira, S., 2014. Identification of selection signatures in livestock species. Genet. Mol. Biol. 37, 330-342.

Dong, S., He, W., Ji, J., Zhang, C., Guo, Y.,Yang, T., 2021. Ldblockshow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files. Brief Bioinform. 22, 1477-4054.

Dzomba, E., Chimonyo, M., Snyman, M.,Muchadeyi, F., 2020. The genomic architecture of South African mutton, pelt, dual-purpose and nondescript sheep breeds relative to global sheep populations. Anim. Genet. 51, 910-923.

Esmaeili-Fard, S., Gholizadeh, M., Hafezian, S.,Abdollahi-Arpanahi, R., 2021. Genome-wide association study and pathway analysis identify NTRK2 as a novel candidate gene for litter size in sheep. PLoS One. 16, e0244408.

Faucher, L., Gode, C.,Arnaud, J., 2016. Development of nuclear microsatellite loci and mitochondrial single nucleotide polymorphisms for the natterjack toad, bufo (epidalea) calamita (bufonidae), using next generation sequencing and competitive allele specific PCR (KASPar). J. Hered. 107, 660-665.

Feng, X., Li, F., Wang, F., Zhang, G., Pang, J., Ren, C., Zhang, T., Yang, H., Wang, Z.,Zhang, Y., 2018. Genome-wide differential expression profiling of mRNAs and IncRNAs associated with prolificacy in Hu sheep. Bioscience Rep. 38.

Galloway, S., McNatty, K., Cambridge, L., Laitinen, M., Juengel, J., Jokiranta, T., McLaren, R., Luiro, K., Dodds, K., Montgomery, G., et al., 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet. 25, 279-283.

Geng, R.Q., Chang, H., Yang, Z.P., Sun, W., Wang, L.P., Lu, S.X., Tsunoda, K.,Ren, Z.J., 2003. Study on origin and phylogeny status of Hu sheep. Asian Australas. J. Anim. Sci. 16, 743-747.

Getachew, T., Haile, A., Meszaros, G., Rischkowsky, B., Huson, H.J., Gizaw, S., Wurzinger, M., Mwai, A.O.,Solkner, J., 2020. Genetic diversity, population structure and runs of homozygosity in ethiopian short fat-tailed and Awassi sheep breeds using genome-wide 50k SNP markers. Livest. Sci. 232, 103899.

Hammond, R., Pahl, M., Su, C., Cousminer, D., Leonard, M., Lu, S., Doege, C., Wagley, Y., Hodge, K., Lasconi, C., et al., 2021. Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci. eLife. 10, e62206.

Hernandez-Montiel, W., Martinez-Nunez, M., Ramon-Ugalde, J., Roman-Ponce, S., Calderon-Chagoya, R.,Zamora-Bustillos, R., 2020. Genome-wide association study reveals candidate genes for litter size traits in Pelibuey sheep. Animals-Basel. 10, 434.

Hu, Z., Park, C.,Reecy, J., 2016. Developmental progress and current status of the animal QTLdb. Nucleic Acids Res. 44, D827-D833.

Huang, d.W., Sherman, B.,Lempicki, R., 2009. Systematic and integrative analysis of large gene lists using david bioinformatics resources. Nat. Protoc. 4, 44-57.

Ji, Z., Chen, J., Gao, W., Zhang, J., Quan, F., Hu, J., Yuan, B.,Ren, W., 2017. Cutaneous transcriptome analysis in NIH hairless mice. PLoS One. 12, e0182463.

Justice, A., North, K., Loos, R., Vedantam, S., Day, F., Berndt, S., Gustafsson, S., Locke, A., Powell, C.,Bratati, K. 2013. Meta-analysis of genetic associations in up to 339,224 individuals identify 66 new loci for BMI, confirming a neuronal contribution to body weight regulation and implicating several novel pathways. Circulation. A050-A050.

Kim, J., Hanotte, O., Mwai, O., Dessie, T., Bashir, S., Diallo, B., Agaba, M., Kim, K., Kwak, W., Sung, S., et al., 2017. The genome landscape of indigenous african cattle. Genome Biol. 18, 34.

Kim, S., Choi, Y., Spencer, T.,Bazer, F., 2003. Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (cox-2) in ovine endometrium. Reprod. Biol. Endocrinol. 1, 58.

Kodama, Y., Shumway, M., Leinonen, R.,International Nucleotide Sequence Database Collaboration, 2011. The sequence read archive: explosive growth of sequencing data. Nucleic Acids Res. 40, D54-D56.

Kumar, R., Ramteke, P., Nath, A., Pramod, R.K., Singh, S.P., Sharma, S.K.,Kumar, S., 2013. Role of candidate genes regulating uterine prostaglandins biosynthesis for maternal recognition of pregnancy in domestic animals. ISRN Physiol. 2013.

Kurita, T., Wang, Y., Donjacour, A., Zhao, C., Lydon, J., O'Malley, B., Isaacs, J., Dahiya, R.,Cunha, G., 2001. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ. 8, 192-200.

Li, D., Zhang, L., Wang, Y., Chen, X., Li, F., Yang, L., Cui, J., Li, R., Cao, B., An, X., et al., 2022. FecB mutation and litter size are associated with a 90-base pair deletion in BMPR1B in East Friesian and Hu crossbred sheep. Anim. Biotechnol. 34, 1314-1323.

Li, H.,Durbin, R., 2009. Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics. 25, 1754-1760.

Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R.,Subgroup, G.P.D.P., 2009. The sequence alignment/map format and SAMtools. Bioinformatics. 25, 2078-2079.

Li, M., Chen, L., Tian, S., Lin, Y., Tang, Q., Zhou, X., Li, D., Yeung, C., Che, T., Jin, L., et al., 2017. Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies. Genome Res. 27, 865-874.

Li, X., Yang, J., Shen, M., Xie, X., Liu, G., Xu, Y., Lv, F., Yang, H., Yang, Y., Liu, C., et al., 2020. Whole-genome resequencing of wild and domestic sheep identifies genes associated with morphological and agronomic traits. Nat. Commun. 11, 2815.

Liggins, G.,Grieves, S., 1971. Possible role for prostaglandin F_2α in parturition in sheep. Nature. 232, 629-631.

Litwinczuk, Z., Florek, M., Kedzierska-Matysek, M.,Skalecki, P., 2009. Blood haematological profile and meat colour of calves slaughtered in summer and autumn season. Pol. J. Vet. Sci. 12, 557-562.

Lobo, A., Lobo, R.,Paiva, S., 2009. Aromatase gene and its effects on growth, reproductive and maternal ability traits in a multibreed sheep population from Brazil. Genet. Mol. Biol. 32, 484-490.

Lukic, B., Curik, I., Drzaic, I., Galic, V., Shihabi, M., Vostry, L.,Cubric-Curik, V., 2023. Genomic signatures of selection, local adaptation and production type characterisation of east adriatic sheep breeds. J. Anim. Sci. Biotechnol. 14, 142.

Lv, F., Cao, Y., Liu, G., Luo, L., Lu, R., Liu, M., Li, W., Zhou, P., Wang, X., Shen, M., et al., 2022. Whole-genome resequencing of worldwide wild and domestic sheep elucidates genetic diversity, introgression, and agronomically important loci. Mol. Biol. Evol. 39, 1537-1719.

Lv, F., Peng, W., Yang, J., Zhao, Y., Li, W., Liu, M., Ma, Y., Zhao, Q., Yang, G., Wang, F., et al., 2015. Mitogenomic meta-analysis identifies two phases of migration in the history of eastern eurasian sheep. Mol. Biol. Evol. 32, 2515-2533.

McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al., 2010. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297-1303.

Muigai, A.W.T.,Hanotte, O., 2013. The origin of African sheep: archaeological and genetic perspectives. Afr. Archaeol. Rev. 30, 39-50.

Palliser, H., Ooi, G., Hirst, J., Rice, G., Dellios, N., Escalona, R.,Young, I., 2004. Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep. J. Endocrinol. 180, 469-477.

Patterson, N., Price, A.,Reich, D., 2006. Population structure and eigenanalysis. PLoS Genet. 2, e190.

Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M., Bender, D., Maller, J., Sklar, P., de Bakker, P., Daly, M., et al., 2007. Plink: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575.

Qanbari, S., Pimentel, E., Tetens, J., Thaller, G., Lichtner, P., Sharifi, A.,Simianer, H., 2010. A genome-wide scan for signatures of recent selection in Holstein cattle. Anim. Genet. 41, 377-389.

Sabeti, P., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., Xie, X., Byrne, E., McCarroll, S., Gaudet, R., et al., 2007. Genome-wide detection and characterization of positive selection in human populations. Nature. 449, 913-918.

Shakhin, A.V., Dotsev, A.V., Deniskova, T.E., Gottfried, B.,Zinovieva, N.A., 2021. Psxii-2 identification of candidate SNPs associated with high prolificacy in Romanov sheep. J. Anim. Sci. 99, 254-255.

Shi, H., Li, T., Su, M., Wang, H., Li, Q., Lang, X.,Ma, Y., 2023. Whole genome sequencing revealed genetic diversity, population structure, and selective signature of Panou Tibetan sheep. BMC Genom. 24, 50.

Simpson, E., Mahendroo, M., Means, G., Kilgore, M., Hinshelwood, M., Graham-Lorence, S., Amarneh, B., Ito, Y., Fisher, C.,Michael, M., 1994. Aromatase cytochrome p450, the enzyme responsible for estrogen biosynthesis. Endocr. Rev. 15, 342-355.

Sun, W., Chang, H., Yang, Z.P., Geng, R.Q., Lu, S.X., Chang, G.B., Xu, W., Wang, H.Y., Ren, Z.J.,Tsunoda, K., 2002. Studies on the genetic relationships of sheep populations from east and south of central asia. Asian Australas. J. Anim. Sci. 15, 1398-1402.

Szpiech, Z.,Hernandez, R., 2014. selscan: an efficient multithreaded program to perform EHH-based scans for positive selection. Mol. Biol. Evol. 31, 2824-2827.

Tajima, F., 1989. DNA polymorphism in a subdivided population: the expected number of segregating sites in the two-subpopulation model. Genetics. 123, 229-240.

Tang, J., Hu, W., Di, R., Liu, Q., Wang, X., Zhang, X., Zhang, J.,Chu, M., 2018. Expression analysis of the prolific candidate genes, BMPR1B, BMP15, and GDF9 in Small Tail Han Ewes with three fecundity (FecB gene) genotypes. Animals-Basel. 8.

Tapio, M., Marzanov, N., Ozerov, M., Cinkulov, M., Gonzarenko, G., Kiselyova, T., Murawski, M., Viinalass, H.,Kantanen, J., 2006. Sheep mitochondrial DNA variation in european, caucasian, and central asian areas. Mol. Biol. Evol. 23, 1776-1783.

Tullis, J.L., 1952. Separation and purification of leukocytes and platelets. Blood. 7, 891-896.

Vilella, A., Severin, J., Ureta-Vidal, A., Heng, L., Durbin, R.,Birney, E., 2009. EnsemblCompara geneTrees: complete, duplication-aware phylogenetic trees in vertebrates. Genome Res. 19, 327-335.

Voight, B., Kudaravalli, S., Wen, X.,Pritchard, J., 2006. A map of recent positive selection in the human genome. PLoS Biol. 4, e72.

Wang, C., Wang, H., Zhang, Y., Tang, Z., Li, K.,Liu, B., 2015. Genome-wide analysis reveals artificial selection on coat colour and reproductive traits in Chinese domestic pigs. Mol. Ecol. Resour. 15, 414-424.

Wang, M., Zhang, R., Su, L., Li, Y., Peng, M., Liu, H., Zeng, L., Irwin, D., Du, J., Yao, Y., et al., 2016. Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication. Cell Res. 26, 556-573.

Wang, W., Zhang, X., Zhou, X., Zhang, Y., La, Y., Zhang, Y., Li, C., Zhao, Y., Li, F., Liu, B., et al., 2019. Deep genome resequencing reveals artificial and natural selection for visual deterioration, plateau adaptability and high prolificacy in Chinese domestic sheep. Front. Genet. 10, 300.

Wei, C., Wang, H., Liu, G., Wu, M., Cao, J., Liu, Z., Liu, R., Zhao, F., Zhang, L., Lu, J., et al., 2015. Genome-wide analysis reveals population structure and selection in Chinese indigenous sheep breeds. BMC Genom. 16, 194.

Weir, B.,Cockerham, C., 1984. Estimating f-statistics for the analysis of population structure. Evolution. 38, 1358-1370.

Wen, Y.L., Guo, X.F., Ma, L., Zhang, X.S.,Chu, M.X., 2021. The expression and mutation of BMPR1B and its association with litter size in small-tail Han sheep (Ovis aries). Arch. Anim. Breed. 64, 211-221.

Xiao, C., Murphy, B., Sirois, J.,Goff, A., 1999. Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-tau in bovine endometrial cells. Biol. Reprod. 60, 656-663.

Xu, D., Wang, X., Zhang, X., Li, F., Zhang, D., Li, X., Zhang, Y., Zhao, Y., Song, Q., Cheng, J., et al., 2021. Polymorphisms in the ovine GP5 gene associated with blood physiological indices. Anim. Biotechnol. 34, 1132-1142.

Yang, M., Fu, J., Lan, X., Sun, Y., Lei, C., Zhang, C.,Chen, H., 2013. Effect of genetic variations within the SH2B2 gene on the growth of Chinese cattle. Gene. 528, 314-319.

Yu, M., Li, L., Liu, M., Wang, L., Gao, X., Zhou, L., Liu, N.,He, J., 2022. Mir-27a targeting PIK3R3 regulates the proliferation and apoptosis of sheep hair follicle stem cells. Animals-Basel. 13, 141.

Yu, Y., Fu, J., Xu, Y., Zhang, J., Ren, F., Zhao, H., Tian, S., Guo, W., Tu, X., Zhao, J., et al., 2018. Genome re-sequencing reveals the evolutionary history of peach fruit edibility. Nat. Commun. 9, 5404.

Zhang, C., Dong, S., Xu, J., He, W.,Yang, T., 2019a. PopLDdecay: a fast and effective tool for linkage disequilibrium decay analysis based on variant call format files. Bioinformatics. 35, 1786-1788.

Zhang, D., Zhang, X., Li, F., Yuan, L., Li, X., Zhang, Y., Zhao, Y., Zhao, L., Wang, J., Xu, D., et al., 2022. Whole-genome resequencing reveals molecular imprints of anthropogenic and natural selection in wild and domesticated sheep. Zool. Res. 43, 695-705.

Zhang, Z., Liu, Q., Di, R., Hu, W., Wang, X., He, X., Ma, L.,Chu, M., 2019b. Single nucleotide polymorphisms in BMP2 and BMP7 and the association with litter size in small tail Han sheep. Anim. Reprod. Sci. 204, 183-192.

Zhao, F.-p., Wei, C.-h., Zhang, L., Liu, J.-s., Wang, G.-k., Zeng, T.,Du, L.-x., 2016. A genome scan of recent positive selection signatures in three sheep populations. J. Integr. Agric. 15, 162-174.

Zhao, L., Li, F., Zhang, X., Zhang, D., Li, X., Zhang, Y., Zhao, Y., Song, Q., Huang, K., Xu, D., et al., 2022. Integrative analysis of transcriptomics and proteomics of longissimus thoracis of the Hu sheep compared with the Dorper sheep. Meat Sci. 193, 108930.

Relative Articles

Supplements(0)

Cited By

Proportional views