Skip to main content
SpringerLink
Log in

An ancient positively selected BMPRIB missense variant increases litter size of Mongolian sheep populations following latitudinal gradient

  • Original Article
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

New gene mutation origination is a driving force for the evolution of organisms. The effect of FecB mutation in BMPRIB gene on the litter size of sheep has been well known for a long time, each copy of the mutant allele increases litter size by 0.4–0.5. However, the origin and adaptive evolution mechanism of FecB mutation are still unclear. Here we carried on the thorough analysis on evolutionary features of BMPRIB gene and found that 150 species as a whole is under purifying selection while sheep lineage shows evidence of positive selection. The results of allele age estimation revealed that the FecB mutation in Mongolian sheep of China originated in Mongolian Plateau at about 5000 years ago. Due the two shape drops in temperature subsequently, Mongolian sheep migrated from north to south following the northern nomadic people. Accordingly, the FecB mutant allele frequency increased, with the lowest in sheep locating at Mongolian plateau (0.01) and the highest in sheep locating at Yangtze River valley (0.96). In conclusion, the FecB mutation in Mongolian sheep of China originated in Mongolian Plateau at about 5000 years ago, and the differentiated litter size of Mongolian sheep might be the result of adaptation to various environments during the migration following latitudinal gradient. This study may well exemplify selection on an ancient variation triggered by drastic ecological shifts, and is also helpful to analyze the adaptive evolution mechanism of economic traits of domestic animals and identify major genes and molecular markers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The whole genome resequencing datasets of 40 Hu sheep supporting the conclusions of this article have been submitted to the NCBI Sequence Read Archive under BioProject ID PRJNA675390. The whole genome resequencing datasets of 59 sheep from NCBI database supporting the conclusions of this article are available in the NCBI Sequence Read Archive under accession number SRP066883 (Pan et al. 2018).

References

  • Antao T, Lopes A, Lopes RJ, Beja-Pereira A, Luikart G (2008) Lositan: a workbench to detect molecular adaptation based on a Fst-outlier method. BMC Bioinform 9:1–5

    Article  Google Scholar 

  • Balduzzi S, Rücker G, Schwarzer G (2019) How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health 22:153–160

    Article  PubMed  Google Scholar 

  • Booker TR, Jackson BC, Keightley PD (2017) Detecting positive selection in the genome. BMC Biol 15:98

    Article  PubMed  PubMed Central  Google Scholar 

  • Chandrasekaran C, Betrán E (2008) Origins of new genes and pseudogenes. Nat Educ 1:181

    Google Scholar 

  • Chen SY, Duan ZY, Sha T, Xiang YJ, Wu SF et al (2006) Origin, genetic diversity, and population structure of Chinese domestic sheep. Gene 376:216–223

    Article  CAS  PubMed  Google Scholar 

  • Chen XY, Sun HX, Tian SJ, Guo WT (2015) Association of BMPRIB gene with litter size trait and genetic variations in different generations of Hanper mutton sheep. J Agric Univ Hebei 38:99–102

    CAS  Google Scholar 

  • China National Commission of Animal Genetic Resources (2011) Animal genetic resources in China sheep and goats. China Agric Press

  • Chong YQ, Liu GQ, Jiang XP (2019) Effect of BMPRIB gene on litter size of sheep in china: a meta-analysis. Anim Reprod Sci 210:106175

    Article  CAS  PubMed  Google Scholar 

  • Chu MX, Liu ZH, Jiao CL, He YQ, Fang L et al (2007) Mutations in BMPRIB and BMP15 genes are associated with litter size in Small Tailed Han sheep (Ovis aries). J Anim Sci 85:598–603

    Article  CAS  PubMed  Google Scholar 

  • Chu MX, Jia LH, Zhang YJ, Jin M, Chen HQ et al (2011) Polymorphisms of coding region of BMPR-IB gene and their relationship with litter size in sheep. Mol Biol Rep 38:4071–4076

    Article  CAS  PubMed  Google Scholar 

  • Darwin CR (1900) On the origin of species by means of natural selection, or the preservation of favored races in the struggle for life. The origin of species by means of natural selection, or, the preservation of favoured races in the struggle for life. J Murray

  • Davis GH, Montgomery GW, Allison AJ, Kelly RW, Bray AR (1982) Segregation of a major gene influencing fecundity in progeny of Booroola sheep. N Zeal J Agric Res 25:525–529

    Article  Google Scholar 

  • Davis GH (2009) The Booroola gene: origin, distribution, use and management of the FecB mutation. In: Aciar proceedings

  • Depristo MA, Banks E, Poplin R, Garimella KV, Maguire JR et al (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43:491–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR et al (2002) Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci USA 99:309–314

    Article  CAS  PubMed  Google Scholar 

  • Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:1–8

    Article  Google Scholar 

  • Fang D, Wu JP, Xu JF, Luo YR, Zhang LP et al (2010) Research on application effect in breeding of molecular marker in sheep BMPR-IB gene. Xinjiang Agric Sci 47:189–194

    CAS  Google Scholar 

  • Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791

    Article  PubMed  Google Scholar 

  • Galloway SM, Mcnatty KP, Cambridge LM, Laitinen MP, Juengel JL 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

    Article  CAS  PubMed  Google Scholar 

  • García-Gámez E, Goutam S, Gutiérrez-Gil B, Juan-Jose A (2012) Linkage disequilibrium and inbreeding estimation in Spanish Churra sheep. BMC Genet 13:43

    Article  PubMed  PubMed Central  Google Scholar 

  • Gootwine E, Reicher S, Rozov A (2008) Prolificacy and lamb survival at birth in Awassi and Assaf sheep carrying the FecB (Booroola) mutation. Anim Reprod Sci 108:402–411

    Article  PubMed  Google Scholar 

  • Graham B (1996) Selection: the mechanism of evolution. Springer Science Business Media, Dordrecht

    Google Scholar 

  • Guan F, Liu SR, Shi GQ, Yang LG (2007) Polymorphism of FecB gene in nine sheep breeds or strains and its effects on litter size, lamb growth and development. Anim Reprod Sci 99:44–52

    Article  CAS  PubMed  Google Scholar 

  • Guo YL, Xu WS, Gu B, Fang PX (1998) Ecological studies on the historical origin of Hu sheep. Agric Archaeol 3:306–312

    Google Scholar 

  • Hanrahan JP (2004) Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod 70:900–909

    Article  CAS  PubMed  Google Scholar 

  • Holland MM, Parson W (2011) GeneMarker? HID: a reliable software tool for the analysis of forensic STR data. J Forensic Sci 56:29–35

    Article  PubMed  Google Scholar 

  • Holsinger KE, Weir BS (2009) Genetics in geographically structured populations: defining, estimating and interpreting Fst. Nat Rev Genet 10:639–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hua GH, Chen SL, Ai JT, Yang LG (2008) None of polymorphism of ovine fecundity major genes FecB and FecX was tested in goat. Anim Reprod Sci 108:279–286

    Article  CAS  PubMed  Google Scholar 

  • Ihaka R, Gentleman R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5:299–314

    Google Scholar 

  • Kang XL, Liu JL, Liu YQ, Wang SY, Feng DZ (2017) Association between BMPRIB polymorphism and litter size in two sheep groups. Acta Agric Bor Occ Sin 26:497–502

    CAS  Google Scholar 

  • Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) Mega X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547–1549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25:1754–1760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25:2078–2079

    Article  PubMed  PubMed Central  Google Scholar 

  • Li D, Sun W, Ni R, Zhang XN, Zhang YL et al (2012) Genetic diversity of FecB gene and association analysis of its litter size. J Anim Sci Vet Med 31:1–5

    Google Scholar 

  • Lv FH, Peng WF, Yang J, Zhao YX, Li WR et al (2015) Mitogenomic meta-analysis identifies two phases of migration in the history of Eastern Eurasian sheep. Mol Biol Evol 32:2515–2533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mason IL (1984) Evolution of domesticated animals. In: Evolution of domesticated animals

  • Meadows JRS, Li K, Kantanen J, Tapio M, Sipos W, Pardeshi V et al (2005) Mitochondrial sequence reveals high levels of gene flow between breeds of domestic sheep from Asia and Europe. J Hered 96:494–501

    Article  CAS  PubMed  Google Scholar 

  • Meadows JR, Cemal I, Karaca O, Gootwine E, Kijas JW (2007) Five ovine mitochondrial lineages identified from sheep breeds of the Near East. Genetics 175:1371–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263

    Article  CAS  PubMed  Google Scholar 

  • Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P et al (2001) Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc Natl Acad Sci USA 98:5104–5109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nei M, Kumar S (2000) Molecular evolution and phylogenetics. Oxford Univ Pres, Oxford

    Google Scholar 

  • Nicol L, Bishop SC, Pong-Wong R, Bendixen C, Holm LE et al (2009) Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction 138:921–933

    Article  CAS  PubMed  Google Scholar 

  • Pan ZY, Zhang BY, Hu WP, Di R, Lin QY et al (2015) The genetic diversity of both FecB gene and microsatellite gc101is associated with reproduction selection in sheep. Turk J Vet Anim Sci 39:254–260

    Article  CAS  Google Scholar 

  • Pan ZY, Li SD, Liu QY, Wang Z, Zhou ZK et al (2018) Whole-genome sequences of 89 chinese sheep suggest role of rxfp2 in the development of unique horn phenotype as response to semi-feralization. Gigascience 7:1–15

    Article  CAS  Google Scholar 

  • Ren YL, Shen ZQ, Li M, Xiao N, Dong WY et al (2011) Association of polymorphisms in the FecB gene with litter size in Wadi sheep. China Anim Hus Vet Med 38:159–162

    CAS  Google Scholar 

  • Rubin CJ, Zody MC, Eriksson J, Meadows JRS, Sherwood E et al (2010) Whole-genome resequencing reveals loci under selection during chicken domestication. Nature 464:587–591

    Article  CAS  PubMed  Google Scholar 

  • Shao YG, Mirinisahan K, Liu WJ (2012) Study on the relationship between the polymorphism of BMPR-IB gene and litter size in Xinjiang Cele black sheep. China Anim Hus Vet Med 39:221–223

    CAS  Google Scholar 

  • Shi HC, Gao ZY, Niu ZG, Bai J, Feng LJ et al (2011) Detection of FecB mutation and its relationship with litter size in Xinjiang Duolang sheep (Ovis aries). J Agr Biotechnol 19:330–334

    CAS  Google Scholar 

  • Shi HC, Niu ZG, Bai J (2012) Study on the effect of BMPR-IB gene mutation on the litter size of Cele black sheep and its genetic law. Chin J Anim Sci 3:14–17

    Google Scholar 

  • Sieber C, Kopf J, Hiepen C, Knaus P (2009) Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev 20:343–355

    Article  CAS  PubMed  Google Scholar 

  • Slatkin M, Rannala B (2000) Estimating allele age. Annu Rev Genom Hum Genet 1:225–249

    Article  CAS  Google Scholar 

  • Sun HX, Dun WT, Chen XY, Tian SJ, Tan W (2011) Relationship between polymorphism of BMPR-IB gene and litter size and sexual season for different sheep breeds. Hunan Agric Sci 3:147–149

    Google Scholar 

  • Tapio M, Marzanov N, Ozerov M, Cinkulov Gonzarenko MG (2006) Sheep mitochondrial DNA variation in European, Caucasian, and Central Asian areas. Mol Biol Evol 23:1776–1783

    Article  CAS  PubMed  Google Scholar 

  • Tian XE, Sun HX, Wang YJ (2009) Genetic polymorphism of BMPR-IB gene and effect on litter size in three sheep breeds. J Northwest A F Univ Nat Sci Edit 37:31–36

    Google Scholar 

  • Walkden-Brown SW, Van-Der-Werf JH, Chanda N, Gupta V (2009) Use of the FecB (Booroola) gene in sheep-breeding programs. In: Use of the FecB (Booroola) gene in sheep-breeding programs: proceedings of the Helen Newton Turner Memorial International Workshop, Australian Centre for International Agricultural Research (ACIAR)

  • Wang X, Maimaitiyiming BLT (2010) Studies of BMPR-IB gene as a candidate gene for prolificacy in Duolang Sheep. Xinjiang Agric Sci 47:1813–1818

    CAS  Google Scholar 

  • Wang TR, Tang HS (2004) East Asian antiquities, vol A. Cultural Relics Publishing House, Beijing

    Google Scholar 

  • Wang WM, Liu SJ, Li FD, Pan XY, Li C et al (2015) Polymorphisms of the ovine BMPR-IB, BMP-15 and FSHR and their associations with litter size in two Chinese indigenous sheep breeds. Int J Mol Sci 16:11385–11397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang ZG, Wang L, Yu SD (2010) Polymorphism detection and genetic effect analysis on BMPR-IB gene in Hu sheep. In: Symposium of the 15th seminar of animal reproduction branch of Chinese association of animal science and veterinary medicine

  • Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population-structure. Evolution 38:1358–1370

    CAS  PubMed  Google Scholar 

  • Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM et al (2001) Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod 64:1225–1235

    Article  CAS  PubMed  Google Scholar 

  • Xv X, Chen ZD (1990) Holocene environment: environment changes in recent ten thousand years. Guizhou People’s Publishing House, Guiyang

    Google Scholar 

  • Yang ZH (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591

    Article  CAS  PubMed  Google Scholar 

  • Yang ZH, Rodríguez CE (2013) Searching for efficient Markov chain Monte Carlo proposal kernels. Proc Natl Acad Sci USA 110:19307–19312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang ZH, Nielsen R, Goldman N, Pedersen AMK (2000) Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155:431–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Yang YL, Liu SR, Zhong FG, Zhang YS et al (2010) Analysis of single nucleotide polymorphism of BMPR-IB gene in sheep. Acta Agric Bor Occ Sin 19:7–11

    Google Scholar 

  • Yang YZ, Feng T, Chu MX, Yun P, Xiao W et al (2012) FecB mutation of BMPR-IB gene and its association with litter size and growth traits in Small Tailed Han sheep. Acta Agric Bor Occ Sin 27:38–43

    Google Scholar 

  • Yeh F, Yang RC, Boyle T (2000) POPGENE-for the analysis of genetic variation among and within populations using co-dominant and dominant markers

  • Zhao YX, Yang J, Lv FH, Hu XJ, Xie X et al (2017) Genomic reconstruction of the history of native sheep reveals the peopling patterns of nomads and the expansion of early pastoralism in East Asia. Mol Biol Evol 34:2380–2395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou YY, Zhou B, Pache L, Chang M, Khodabakhshi AH et al (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu KZ (1973) Preliminary study on climate change of China in the past five thousand years. Sci China 2:15–38

    Google Scholar 

  • Zhu EY, Shi HC, Wu J, Liu MJ, Jian ZJ et al (2006) Study on bone morphogenetic protein receptor IB as a candidate gene for prolificacy in sheep. Acta Agric Bor Occ Sin 15:20–23

    Google Scholar 

Download references

Acknowledgements

The authors sincerely thank Pro. Mingxing Chu, Yurong Fu, Chenhui Liu and Dongdong Bo for their contribution to the revision of the manuscript.

Funding

This study was supported by the National Key R&D Program of China (2018YFD0502105) and the China Agriculture Research System (CARS-38).

Author information

Author notes

  1. Yuqing Chong and Xunping Jiang have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Yuqing Chong, Xunping Jiang & Guiqiong Liu

  2. Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, Wuhan, 430070, People’s Republic of China

    Yuqing Chong, Xunping Jiang & Guiqiong Liu

Authors
  1. Yuqing Chong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xunping Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guiqiong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YC validation, formal analysis, investigation, data curation, writing—original draft. XJ methodology, formal analysis, data curation, writing—review and editing, funding acquisition. GL conceptualization, methodology, formal analysis, data curation, writing—review and editing.

Corresponding author

Correspondence to Guiqiong Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All animals and procedures involved in this study were reviewed and approved by the Ethical Committee of Huazhong Agricultural University with permission number of HZAUGO-2018-005.

Informed consent

All the authors have consent for publication.

Additional information

Communicated by Joan Cerdá.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1115 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chong, Y., Jiang, X. & Liu, G. An ancient positively selected BMPRIB missense variant increases litter size of Mongolian sheep populations following latitudinal gradient. Mol Genet Genomics 297, 155–167 (2022). https://doi.org/10.1007/s00438-021-01828-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-021-01828-4

Keywords

Search

Navigation