Genome-wide scans for signatures of selection in Mangalarga Marchador horses using high-throughput SNP genotyping.
Abstract: The detection of signatures of selection in genomic regions provides insights into the evolutionary process, enabling discoveries regarding complex phenotypic traits. In this research, we focused on identifying genomic regions affected by different selection pressures, mainly highlighting the recent positive selection, as well as understanding the candidate genes and functional pathways associated with the signatures of selection in the Mangalarga Marchador genome. Besides, we seek to direct the discussion about genes and traits of importance in this breed, especially traits related to the type and quality of gait, temperament, conformation, and locomotor system. Results: Three different methods were used to search for signals of selection: Tajima's D (TD), the integrated haplotype score (iHS), and runs of homozygosity (ROH). The samples were composed of males (n = 62) and females (n = 130) that were initially chosen considering well-defined phenotypes for gait: picada (n = 86) and batida (n = 106). All horses were genotyped using a 670 k Axiom® Equine Genotyping Array (Axiom MNEC670). In total, 27, 104 (chosen), and 38 candidate genes were observed within the signatures of selection identified in TD, iHS, and ROH analyses, respectively. The genes are acting in essential biological processes. The enrichment analysis highlighted the following functions: anterior/posterior pattern for the set of genes (GLI3, HOXC9, HOXC6, HOXC5, HOXC4, HOXC13, HOXC11, and HOXC10); limb morphogenesis, skeletal system, proximal/distal pattern formation, JUN kinase activity (CCL19 and MAP3K6); and muscle stretch response (MAPK14). Other candidate genes were associated with energy metabolism, bronchodilator response, NADH regeneration, reproduction, keratinization, and the immunological system. Conclusions: Our findings revealed evidence of signatures of selection in the MM breed that encompass genes acting on athletic performance, limb development, and energy to muscle activity, with the particular involvement of the HOX family genes. The genome of MM is marked by recent positive selection. However, Tajima's D and iHS results point also to the presence of balancing selection in specific regions of the genome.
© 2021. The Author(s).
Publication Date: 2021-10-14 PubMed ID: 34645387PubMed Central: PMC8515666DOI: 10.1186/s12864-021-08053-8Google Scholar: Lookup
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Summary
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This research article discusses the use of genome-wide scans to identify signs of selective breeding in Mangalarga Marchador horses. The researchers used high-throughput single nucleotide polymorphism (SNP) genotyping to locate regions of the genome affected by selective pressures, primarily recent positive selection, and identified genes and functional pathways associated with these selected traits.
Understanding the Research
- The study sought to identify areas of the genome in Mangalarga Marchador horses that have been impacted by selective pressures. This includes any breed traits related to the type and quality of gait, temperament, physique, and the locomotor system.
- Three analytical methods were employed to identify these selection signals: Tajima’s D, Integrated Haplotype Score (iHS), and Runs of Homozygosity (ROH). These methods help to provide a genomic snapshot of the breed’s history and the selection processes that have shaped their genetic makeup.
- The sampling population consisted of both male and female horses specifically chosen based on their well-defined gait phenotype, labeled as ‘picada’ or ‘batida’.
- The genetic information was obtained using a 670 k Axiom® Equine Genotyping Array, which is a robust tool for high-throughput SNP genotyping.
Results of the Study
- Different genes identified as under positive selection across the three methods. In total, 27 (Tajima’s D), 104 (iHS), and 38 (ROH) candidate genes were caught within the selection signatures.
- These genes were linked to essential biological processes. Among them, several genes (GLI3, HOXC9, HOXC6, HOXC5, HOXC4, HOXC13, HOXC11, and HOXC10) were associated with anterior/posterior pattern formation related to limb development.
- Other genes were found to be involved in skeletal system development, proximal/distal pattern formation, JUN kinase activity, and muscle stretch response, all of which could potentially impact the horse’s athletic performance.
- Additional candidate genes were linked to energy metabolism, bronchodilator response, NADH regeneration (potentially affecting energy availability and utilization), reproduction, keratinization (probably affecting skin or coat traits), and the immunological system.
Conclusions from the Research
- It was concluded that the Mangalarga Marchador horse breed has been significantly shaped by recent positive selection, targeting genes affecting athletic performance, limb development, and energy to muscle activity. Certain HOX family genes, which play a crucial role in organism development, were notably present.
- Notably, the results of Tajima’s D and iHS also indicated the presence of balancing selection in specific genome regions. Balancing selection is a process by which genetic diversity is maintained in a population, suggesting that beside the active selection for certain desired traits, other genomic areas are under selective pressures to maintain variability.
Cite This Article
APA
Santos WB, Schettini GP, Maiorano AM, Bussiman FO, Balieiro JCC, Ferraz GC, Pereira GL, Baldassini WA, Neto ORM, Oliveira HN, Curi RA.
(2021).
Genome-wide scans for signatures of selection in Mangalarga Marchador horses using high-throughput SNP genotyping.
BMC Genomics, 22(1), 737.
https://doi.org/10.1186/s12864-021-08053-8 Publication
Researcher Affiliations
- Department of Animal Science, São Paulo State University (Unesp) - FCAV, Via de Acesso Professor Paulo Donato Castelane, NN, CEP: 14884-900, Jaboticabal, SP, Brazil. wellington.bizarria@unesp.br.
- Department of Animal Science, São Paulo State University (Unesp) - FCAV, Via de Acesso Professor Paulo Donato Castelane, NN, CEP: 14884-900, Jaboticabal, SP, Brazil.
- Department of Animal Science, São Paulo State University (Unesp) - FCAV, Via de Acesso Professor Paulo Donato Castelane, NN, CEP: 14884-900, Jaboticabal, SP, Brazil.
- Department of Animal Science, University of São Paulo (USP) - FZEA, Pirassununga, Brazil.
- Department of Animal Science, University of São Paulo (USP) - FZEA, Pirassununga, Brazil.
- Department of Animal Science, São Paulo State University (Unesp) - FCAV, Via de Acesso Professor Paulo Donato Castelane, NN, CEP: 14884-900, Jaboticabal, SP, Brazil.
- Department of Breeding and Animal Nutrition, São Paulo State University (Unesp) - FMVZ, Botucatu, Brazil.
- Department of Breeding and Animal Nutrition, São Paulo State University (Unesp) - FMVZ, Botucatu, Brazil.
- Department of Breeding and Animal Nutrition, São Paulo State University (Unesp) - FMVZ, Botucatu, Brazil.
- Department of Animal Science, São Paulo State University (Unesp) - FCAV, Via de Acesso Professor Paulo Donato Castelane, NN, CEP: 14884-900, Jaboticabal, SP, Brazil.
- Department of Breeding and Animal Nutrition, São Paulo State University (Unesp) - FMVZ, Botucatu, Brazil.
MeSH Terms
- Animals
- Female
- Genome
- Genotype
- Haplotypes
- Homozygote
- Horses / genetics
- Male
- Polymorphism, Single Nucleotide
- Selection, Genetic
Conflict of Interest Statement
The author(s) certify that they have no conflict of interest.
References
This article includes 62 references
- Andrade LS. A herança genética da marcha: matéria técnica.. 2011.
- ABCCMM . Associação Brasileira de Criadores de Cavalos da Raça Mangalarga. 2018.
- USMMA . U.S. Mangalarga Marchador Association. 2019.
- Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren G, Andersson L, Kullander K. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.. Nature 2012 Aug 30;488(7413):642-6.
- Promerová M, Andersson LS, Juras R, Penedo MC, Reissmann M, Tozaki T, Bellone R, Dunner S, Hořín P, Imsland F, Imsland P, Mikko S, Modrý D, Roed KH, Schwochow D, Vega-Pla JL, Mehrabani-Yeganeh H, Yousefi-Mashouf N, G Cothran E, Lindgren G, Andersson L. Worldwide frequency distribution of the 'Gait keeper' mutation in the DMRT3 gene.. Anim Genet 2014 Apr;45(2):274-82.
- Lewontin RC, Krakauer J. Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms.. Genetics 1973 May;74(1):175-95.
- Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG. Recent and ongoing selection in the human genome.. Nat Rev Genet 2007 Nov;8(11):857-68.
- Bertolini F, Servin B, Talenti A, Rochat E, Kim ES, Oget C. Signatures of selection and environmental adaptation across the goat genome post-domestication.. Genetics Proc Natl Acad Sci USA 2008;105:17659–17664.
- Bamshad M, Wooding SP. Signatures of natural selection in the human genome.. Nat Rev Genet 2003 Feb;4(2):99-111.
- Avila F, Mickelson JR, Schaefer RJ, McCue ME. Genome-Wide Signatures of Selection Reveal Genes Associated With Performance in American Quarter Horse Subpopulations.. Front Genet 2018;9:249.
- Srikanth K, Kim NY, Park W, Kim JM, Kim KD, Lee KT, Son JH, Chai HH, Choi JW, Jang GW, Kim H, Ryu YC, Nam JW, Park JE, Kim JM, Lim D. Comprehensive genome and transcriptome analyses reveal genetic relationship, selection signature, and transcriptome landscape of small-sized Korean native Jeju horse.. Sci Rep 2019 Nov 13;9(1):16672.
- Qanbari S, Simianer H. Mapping signatures of positive selection in the genome of livestock.. Livest Sci 2014;166:133–143.
- de Simoni Gouveia JJ, Paiva SR, McManus CM, Caetano AR, Kijas JW, Facó O. Genome-wide search for signatures of selection in three major Brazilian locally adapted sheep breeds.. Livest Sci 2017;197:36–45.
- Nielsen R. Molecular signatures of natural selection.. Annu Rev Genet 2005;39:197-218.
- Sabeti PC, Reich DE, Higgins JM, Levine HZ, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D, Cooper R, Kwiatkowski D, Ward R, Lander ES. Detecting recent positive selection in the human genome from haplotype structure.. Nature 2002 Oct 24;419(6909):832-7.
- Purfield DC, McParland S, Wall E, Berry DP. The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds.. PLoS One 2017;12(5):e0176780.
- Fariello MI, Boitard S, Naya H, SanCristobal M, Servin B. Detecting signatures of selection through haplotype differentiation among hierarchically structured populations.. Genetics 2013 Mar;193(3):929-41.
- Pérez O'Brien AM, Utsunomiya YT, Mészáros G, Bickhart DM, Liu GE, Van Tassell CP, Sonstegard TS, Da Silva MV, Garcia JF, Sölkner J. Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle.. Genet Sel Evol 2014 Mar 4;46(1):19.
- Carlson CS, Thomas DJ, Eberle MA, Swanson JE, Livingston RJ, Rieder MJ, Nickerson DA. Genomic regions exhibiting positive selection identified from dense genotype data.. Genome Res 2005 Nov;15(11):1553-65.
- Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.. Genetics 1989 Nov;123(3):585-95.
- Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. PLINK: a tool set for whole-genome association and population-based linkage analyses.. Am J Hum Genet 2007 Sep;81(3):559-75.
- Gautier M, Vitalis R. rehh: an R package to detect footprints of selection in genome-wide SNP data from haplotype structure.. Bioinformatics 2012 Apr 15;28(8):1176-7.
- Weigand H, Leese F. Detecting signatures of positive selection in non-model species using genomic data.. Zool J Linnean Soc 2018;184(2):528–583.
- dos Santos BA, Pereira GL, Bussiman F, Bussiman FD, Paschoal VR, de Souza Júnior SM, Balieiro JC. Genomic analysis of the population structure in horses of the Brazilian Mangalarga Marchador breed.. Livest Sci 2019;229:49–55.
- Bizarria Dos Santos W, Pimenta Schettini G, Fonseca MG, Pereira GL, Loyola Chardulo LA, Rodrigues Machado Neto O, Baldassini WA, Nunes de Oliveira H, Abdallah Curi R. Fine-scale estimation of inbreeding rates, runs of homozygosity and genome-wide heterozygosity levels in the Mangalarga Marchador horse breed.. J Anim Breed Genet 2021 Mar;138(2):161-173.
- Gomez-Raya L, Rodríguez C, Barragán C, Silió L. Genomic inbreeding coefficients based on the distribution of the length of runs of homozygosity in a closed line of Iberian pigs.. Genet Sel Evol 2015 Oct 16;47:81.
- Robilliard JJ, Pfau T, Wilson AM. Gait characterisation and classification in horses.. J Exp Biol 2007 Jan;210(Pt 2):187-97.
- Fonseca MG, Ferraz GC, Lage J, Pereira GL. A genome-wide association study reveals differences in the genetic mechanism of control of the two gait patterns of the Brazilian Mangalarga Marchador breed.. J Equine Vet Sci 2017;53:64–67.
- Bussiman FO, dos Santos BA, Abreu Silva BC, Perez BC, Pereira GL, Chardulo LAL. Allelic and genotypic frequencies of the DMRT3 gene in the Brazilian horse breed Mangalarga Marchador and their association with types of gait.. Genet Mol Res 2019;18:gmr18217.
- Jäderkvist Fegraeus K, Hirschberg I, Árnason T, Andersson L, Velie BD, Andersson LS, Lindgren G. To pace or not to pace: a pilot study of four- and five-gaited Icelandic horses homozygous for the DMRT3 'Gait Keeper' mutation.. Anim Genet 2017 Dec;48(6):694-697.
- Arnason T, Van Vleck LD. Genetic improvement of the Horse.. The Genetics of the Horse 2000. p. 341.
- Cadzow M, Boocock J, Nguyen HT, Wilcox P, Merriman TR, Black MA. A bioinformatics workflow for detecting signatures of selection in genomic data.. Front Genet 2014;5:293.
- Ma Y, Ding X, Qanbari S, Weigend S, Zhang Q, Simianer H. Properties of different selection signature statistics and a new strategy for combining them.. Heredity (Edinb) 2015 Nov;115(5):426-36.
- Ablondi M, Viklund Å, Lindgren G, Eriksson S, Mikko S. Signatures of selection in the genome of Swedish warmblood horses selected for sport performance.. BMC Genomics 2019 Sep 18;20(1):717.
- Boitard S, Schlötterer C, Nolte V, Pandey RV, Futschik A. Detecting selective sweeps from pooled next-generation sequencing samples.. Mol Biol Evol 2012 Sep;29(9):2177-86.
- Stapley J, Feulner PGD, Johnston SE, Santure AW, Smadja CM. Variation in recombination frequency and distribution across eukaryotes: patterns and processes.. Philos Trans R Soc Lond B Biol Sci 2017 Dec 19;372(1736).
- Szmatoła T, Gurgul A, Jasielczuk I, Fu W, Ropka-Molik K. A detailed characteristics of bias associated with long runs of homozygosity identification based on medium density SNP microarrays.. J Genomics 2020;8:43-48.
- Ceballos FC, Joshi PK, Clark DW, Ramsay M, Wilson JF. Runs of homozygosity: windows into population history and trait architecture.. Nat Rev Genet 2018 Apr;19(4):220-234.
- Melo D, Marroig G. Directional selection can drive the evolution of modularity in complex traits.. Proc Natl Acad Sci U S A 2015 Jan 13;112(2):470-5.
- Park J, Lee J, Lee DH. Identification of Protein Phosphatase 4 Inhibitory Protein That Plays an Indispensable Role in DNA Damage Response.. Mol Cells 2019 Jul 31;42(7):546-556.
- Golinski ML, Vandhuick T, Derambure C, Fréret M, Lecuyer M, Guillou C, Hiron M, Boyer O, Le Loët X, Vittecoq O, Lequerré T. Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors.. Arthritis Res Ther 2015 Dec 26;17:382.
- Wu X, Guldbrandtsen B, Lund MS, Sahana G. Association analysis for feet and legs disorders with whole-genome sequence variants in 3 dairy cattle breeds.. J Dairy Sci 2016 Sep;99(9):7221-7231.
- Kurz JP, Yang Z, Weiss RB, Wilson DJ, Rood KA, Liu GE, Wang Z. A genome-wide association study for mastitis resistance in phenotypically well-characterized Holstein dairy cattle using a selective genotyping approach.. Immunogenetics 2019 Jan;71(1):35-47.
- Holden LA, Arumilli M, Hytönen MK, Hundi S, Salojärvi J, Brown KH, Lohi H. Assembly and Analysis of Unmapped Genome Sequence Reads Reveal Novel Sequence and Variation in Dogs.. Sci Rep 2018 Jul 18;8(1):10862.
- Akam M. Hox genes and the evolution of diverse body plans.. Philos Trans R Soc Lond B Biol Sci 1995 Sep 29;349(1329):313-9.
- Pineault KM, Wellik DM. Hox genes and limb musculoskeletal development.. Curr Osteoporos Rep 2014 Dec;12(4):420-7.
- Wang B, Fallon JF, Beachy PA. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb.. Cell 2000 Feb 18;100(4):423-34.
- Grilz-Seger G, Neuditschko M, Ricard A, Velie B, Lindgren G, Mesarič M, Cotman M, Horna M, Dobretsberger M, Brem G, Druml T. Genome-Wide Homozygosity Patterns and Evidence for Selection in a Set of European and Near Eastern Horse Breeds.. Genes (Basel) 2019 Jun 28;10(7).
- Aronson D, Boppart MD, Dufresne SD, Fielding RA, Goodyear LJ. Exercise stimulates c-Jun NH2 kinase activity and c-Jun transcriptional activity in human skeletal muscle.. Biochem Biophys Res Commun 1998 Oct 9;251(1):106-10.
- Boyle EA, Li YI, Pritchard JK. An Expanded View of Complex Traits: From Polygenic to Omnigenic.. Cell 2017 Jun 15;169(7):1177-1186.
- Beeson SK, Schaefer RJ, Mason VC, McCue ME. Robust remapping of equine SNP array coordinates to Eq쪳.. Anim Genet 2019 Feb;50(1):114-115.
- Ferenčaković M, Sölkner J, Curik I. Estimating autozygosity from high-throughput information: effects of SNP density and genotyping errors.. Genet Sel Evol 2013 Oct 29;45(1):42.
- Pook T, Mayer M, Geibel J, Weigend S, Cavero D, Schoen CC, Simianer H. Improving Imputation Quality in BEAGLE for Crop and Livestock Data.. G3 (Bethesda) 2020 Jan 7;10(1):177-188.
- Zhang C, Dong SS, Xu JY, He WM, Yang TL. PopLDdecay: a fast and effective tool for linkage disequilibrium decay analysis based on variant call format files.. Bioinformatics 2019 May 15;35(10):1786-1788.
- Paradis E. pegas: an R package for population genetics with an integrated-modular approach.. Bioinformatics 2010 Feb 1;26(3):419-20.
- Paradis E, Schliep K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R.. Bioinformatics 2019 Feb 1;35(3):526-528.
- Wickham H. ggplot2: Elegant Graphics for Data Analysis.. 2016.
- Yu F, Keinan A, Chen H, Ferland RJ, Hill RS, Mignault AA, Walsh CA, Reich D. Detecting natural selection by empirical comparison to random regions of the genome.. Hum Mol Genet 2009 Dec 15;18(24):4853-67.
- Gautier M, Klassmann A, Vitalis R. rehh 2.0: a reimplementation of the R package rehh to detect positive selection from haplotype structure.. Mol Ecol Resour 2017 Jan;17(1):78-90.
- Ceballos FC, Hazelhurst S, Ramsay M. Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data.. BMC Genomics 2018 Jan 30;19(1):106.
- Smedley D, Haider S, Ballester B, Holland R, London D, Thorisson G, Kasprzyk A. BioMart--biological queries made easy.. BMC Genomics 2009 Jan 14;10:22.
- Hu JX, Zhao H, Zhou HH. False Discovery Rate Control With Groups.. J Am Stat Assoc 2010 Sep 1;105(491):1215-1227.
Citations
This article has been cited 2 times.- Dementieva N, Nikitkina E, Shcherbakov Y, Nikolaeva O, Mitrofanova O, Ryabova A, Atroshchenko M, Makhmutova O, Zaitsev A. The Genetic Diversity of Stallions of Different Breeds in Russia.. Genes (Basel) 2023 Jul 24;14(7).
- Abondio P, Cilli E, Luiselli D. Inferring Signatures of Positive Selection in Whole-Genome Sequencing Data: An Overview of Haplotype-Based Methods.. Genes (Basel) 2022 May 22;13(5).
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