Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

English version České info

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F_ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

Vyšlo v časopise: Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003211
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003211

Souhrn

Zdroje

1. LippoldS, MatzkeNJ, ReissmannM, HofreiterM (2011) Whole mitochondrial genome sequencing of domestic horses reveals incorporation of extensive wild horse diversity during domestication. BMC Evol Biol 11 : 328.

2. LudwigA, PruvostM, ReissmannM, BeneckeN, BrockmannGA, et al. (2009) Coat color variation at the beginning of horse domestication. Science 324 : 485.

3. OutramAK, StearNA, BendreyR, OlsenS, KasparovA, et al. (2009) The earliest horse harnessing and milking. Science 323 : 1332–1335.

4. AkeyJM, RuheAL, AkeyDT, WongAK, ConnellyCF, et al. (2010) Tracking footprints of artificial selection in the dog genome. PNAS 107 : 1160–1165.

5. OlssonM, MeadowsJR, TruveK, Rosengren PielbergG, PuppoF, et al. (2011) A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLoS Genet 7: e1001332 doi:10.1371/journal.pgen.1001332.

6. BoykoAR, QuignonP, LiL, SchoenebeckJJ, DegenhardtJD, et al. (2010) A simple genetic architecture underlies morphological variation in dogs. PLoS Biol 8: e1000451 doi:10.1371/journal.pbio.1000451.

7. PollingerJP, BustamanteCD, Fledel-AlonA, SchmutzS, GrayMM, et al. (2005) Selective sweep mapping of genes with large phenotypic effects. Genome Res 15 : 1809–1819.

8. QuilezJ, ShortAD, MartinezV, KennedyLJ, OllierW, et al. (2011) A selective sweep of >8 Mb on chromosome 26 in the Boxer genome. BMC Genomics 12.

9. VaysseA, RatnakumarA, DerrienT, AxelssonE, Rosengren PielbergG, et al. (2011) Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping. PLoS Genet 7: e1002316 doi:10.1371/journal.pgen.1002316.

10. BarendseW, HarrisonBE, BunchRJ, ThomasMB, TurnerLB (2009) Genome wide signatures of positive selection: the comparison of independent samples and the identification of regions associated to traits. BMC Genomics 10 : 178.

11. ConsortiumTBH, GibbsRA, TaylorJF, Van TassellCP, BarendseW, et al. (2009) Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science 324 : 528–532.

12. QanbariS, GianolaD, HayesB, SchenkelF, MillerS, et al. (2011) Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle. BMC Genomics 12 : 318.

13. QanbariS, PimentelEC, TetensJ, ThallerG, LichtnerP, et al. (2010) A genome-wide scan for signatures of recent selection in Holstein cattle. Anim Genet 41 : 377–389.

14. KijasJW, LenstraJA, HayesB, BoitardS, Porto NetoLR, et al. (2012) Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biol 10: e1001258 doi:10.1371/journal.pbio.1001258.

15. GuJ, OrrN, ParkSD, KatzLM, SulimovaG, et al. (2009) A genome scan for positive selection in thoroughbred horses. PLoS ONE 4: e5767 doi:10.1371/journal.pone.0005767.

16. MarklundL, MollerMJ, SandbergK, AnderssonL (1996) A missense mutation in the gene for melanocyte-stimulating hormone receptor (MC1R) is associated with the chestnut coat color in horses. Mamm Genome 7 : 895–899.

17. McCueME, BannaschDL, PetersenJL, GurrJ, BaileyE, et al. (2012) A high density SNP array for the domestic horse and extant perissodactyla: utility for association mapping, genetic diversity, and phylogeny studies. PLoS Genet 8: e1002451 doi:10.1371/journal.pgen.1002451.

18. Bricker SJ, Penedo MCT, Millon LV, Murray JD. Linkage of the dun coat color locus to microsatellites on horse chomoromse 8; 2003; San Diego, CA.

19. HillEW, McGivneyBA, GuJJ, WhistonR, MacHughDE (2010) A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses. BMC Genomics 11.

20. HillEW, GuJ, EiversSS, FonsecaRG, McGivneyBA, et al. (2010) A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PLoS ONE 5: e8645 doi:10.1371/journal.pone.0008645.

21. Dall'OlioS, FontanesiL, Nanni CostaL, TassinariM, MinieriL, et al. (2010) Analysis of horse myostatin gene and identification of single nucleotide polymorphisms in breeds of different morphological types. J Biomed Biotechnol ID542945.

22. ClopA, MarcqF, TakedaH, PirottinD, TordoirX, et al. (2006) A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38 : 813–818.

23. GrobetL, MartinLJ, PonceletD, PirottinD, BrouwersB, et al. (1997) A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet 17 : 71–74.

24. McPherronAC, LeeSJ (1997) Double muscling in cattle due to mutations in the myostatin gene. PNAS 94 : 12457–12461.

25. MosherDS, QuignonP, BustamanteCD, SutterNB, MellershCS, et al. (2007) A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet 3: e79 doi:10.1371/journal.pgen.0030079.

26. SchuelkeM, WagnerKR, StolzLE, HubnerC, RiebelT, et al. (2004) Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 350 : 2682–2688.

27. LindholmA, PiehlK (1974) Fibre composition, enzyme activity and concentrations of metabolites and electrolytes in muscles of standardbred horses. Acta Veterinaria Scandinavica 15 : 287–309.

28. GalisteoAM, AgueraE, MonterdeJG, MiroF (1992) Gluteus-Medius Muscle-Fiber Type Composition in Young Andalusian and Arabian Horses. J Equine Vet Sci 12 : 254–258.

29. LehnhardRA, McKeeverKH, KearnsCF, BeekleyMD (2004) Myosin heavy chain profiles and body composition are different in old versus young Standardbred mares. Vet J 167 : 59–66.

30. RoneusM (1993) Muscle characteristics in standardbreds of different ages and sexes. Equine Vet J 25 : 143–146.

31. RoneusM, LindholmA, AsheimA (1991) Muscle characteristics in Thoroughbreds of different ages and sexes. Equine Vet J 23 : 207–210.

32. SabetiPC, ReichDE, HigginsJM, LevineHZ, RichterDJ, et al. (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419 : 832–837.

33. BrunbergE, AnderssonL, CothranG, SandbergK, MikkoS, et al. (2006) A missense mutation in PMEL17 is associated with the Silver coat color in the horse. BMC Genet 7 : 46.

34. CookD, BrooksS, BelloneR, BaileyE (2008) Missense mutation in exon 2 of SLC36A1 responsible for champagne dilution in horses. PLoS Genet 4: e1000195 doi:10.1371/journal.pgen.1000195.

35. MariatD, TaouritS, GuerinG (2003) A mutation in the MATP gene causes the cream coat colour in the horse. Genet Sel Evol 35 : 119–133.

36. ReissmannM, BierwolfJ, BrockmannGA (2007) Two SNPs in the SILV gene are associated with silver coat colour in ponies. Anim Genet 38 : 1–6.

37. RiederS, TaouritS, MariatD, LangloisB, GuerinG (2001) Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mamm Genome 12 : 450–455.

38. Rosengren PielbergG, GolovkoA, SundstromE, CurikI, LennartssonJ, et al. (2008) A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat Genet 40 : 1004–1009.

39. TerryRB, ArcherS, BrooksS, BernocoD, BaileyE (2004) Assignment of the appaloosa coat colour gene (LP) to equine chromosome 1. Anim Genet 35 : 134–137.

40. Hendricks BL (2007) International Encyclopedia of Horse Breeds. Norman: University of Oklahoma Pres. 486 p.

41. Weatherley L (1978) Great Horses of Britain. Hindhead: Spur Publications. viii, 269 p.

42. LeeSJ (2004) Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol 20 : 61–86.

43. GirgenrathS, SongK, WhittemoreLA (2005) Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow -⁠ and fast-type skeletal muscle. Muscle Nerve 31 : 34–40.

44. HennebryA, BerryC, SiriettV, O'CallaghanP, ChauL, et al. (2009) Myostatin regulates fiber-type composition of skeletal muscle by regulating MEF2 and MyoD gene expression. Am J Physiol Cell Physiol 296: C525–534.

45. WegnerJ, AlbrechtE, FiedlerI, TeuscherF, PapsteinHJ, et al. (2000) Growth -⁠ and breed-related changes of muscle fiber characteristics in cattle. J Anim Sci 78 : 1485–1496.

46. BinnsMM, BoehlerDA, LambertDH (2010) Identification of the myostatin locus (MSTN) as having a major effect on optimum racing distance in the Thoroughbred horse in the USA. Anim Genet 41 Suppl 2 : 154–158.

47. HillEW, FonsecaRG, McGivneyBA, GuJ, MacHughDE, et al. (2012) MSTN genotype (g.66493737C/T) association with speed indices in Thoroughbred racehorses. J Appl Phys 112 : 86–90.

48. TozakiT, HillEW, HirotaK, KakoiH, GawaharaH, et al. (2012) A cohort study of racing performance in Japanese Thoroughbred racehorses using genome information on ECA18. Anim Genet 43 : 42–52.

49. TozakiT, SatoF, HillEW, MiyakeT, EndoY, et al. (2011) Sequence Variants at the myostatin Gene Locus Influence the Body Composition of Thoroughbred Horses. J Vet Med Sci 73 : 1617–1624.

50. ElashryMI, OttoA, MatsakasA, El-MorsySE, PatelK (2009) Morphology and myofiber composition of skeletal musculature of the forelimb in young and aged wild type and myostatin null mice. Rejuv Res 12 : 269–281.

51. McGivneyBA, BrowneJA, FonsecaRG, KatzLM, MacHughDE, et al. (2012) MSTN genotypes in Thoroughbred horses influence skeletal muscle gene expression and racetrack performance. Anim Genet 43 : 810–812.

52. AllenDL, UntermanTG (2007) Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol 292: C188–199.

53. GuimaraesSEF, StahlCH, LonerganSM, GeigerB, RothschildMF (2007) Myostatin promoter analysis and expression pattern in pigs. Livestock Sci 112 : 143–150.

54. SalernoMS, ThomasM, ForbesD, WatsonT, KambadurR, et al. (2004) Molecular analysis of fiber type-specific expression of murine myostatin promoter. Am J Physiol Cell Physiol 287: C1031–1040.

55. SpillerMP, KambadurR, JeanplongF, ThomasM, MartynJK, et al. (2002) The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD. Mol Cell Biol 22 : 7066–7082.

56. RaymondCS, ShamuCE, ShenMM, SeifertKJ, HirschB, et al. (1998) Evidence for evolutionary conservation of sex-determining genes. Nature 391 : 691–695.

57. YiW, ZarkowerD (1999) Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms. Development 126 : 873–881.

58. HongCS, ParkBY, Saint-JeannetJP (2007) The function of Dmrt genes in vertebrate development: it is not just about sex. Dev Biol 310 : 1–9.

59. AnderssonLS, LarhammarM, MemicF, WootzH, SchwochowD, et al. (2012) Mutations in DMRT3 alter locomotion in horses and spinal circuit function in mice. Nature 488 : 642–646.

60. ThiruvenkadanAK, KandasamyN, PanneerselvamS (2009) Inheritance of racing performance of trotter horses: An overview. Livestock Sci 124 : 163–181.

61. GuJ, MacHughDE, McGivneyBA, ParkSD, KatzLM, et al. (2010) Association of sequence variants in CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses. Equine Vet J 42 Suppl 38 : 569–575.

62. HillEW, GuJ, McGivneyBA, MacHughDE (2010) Targets of selection in the Thoroughbred genome contain exercise-relevant gene SNPs associated with elite racecourse performance. Anim Genet 41 Suppl 2 : 56–63.

63. ChaseK, JonesP, MartinA, OstranderEA, LarkKG (2009) Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic. J Hered 100 Suppl 1: S37–41.

64. JonesP, ChaseK, MartinA, DavernP, OstranderEA, et al. (2008) Single-nucleotide-polymorphism-based association mapping of dog stereotypes. Genetics 179 : 1033–1044.

65. SutterNB, BustamanteCD, ChaseK, GrayMM, ZhaoK, et al. (2007) A single IGF1 allele is a major determinant of small size in dogs. Science 316 : 112–115.

66. EberleinA, TakasugaA, SetoguchiK, PfuhlR, FlisikowskiK, et al. (2009) Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-SMC condensin I complex, subunit G (NCAPG) gene. Genetics 183 : 951–964.

67. SetoguchiK, FurutaM, HiranoT, NagaoT, WatanabeT, et al. (2009) Cross-breed comparisons identified a critical 591-kb region for bovine carcass weight QTL (CW-2) on chromosome 6 and the Ile-442-Met substitution in NCAPG as a positional candidate. BMC Genet 10 : 43.

68. SetoguchiK, WatanabeT, WeikardR, AlbrechtE, KuhnC, et al. (2011) The SNP c.1326T>G in the non-SMC condensin I complex, subunit G (NCAPG) gene encoding a p.Ile442Met variant is associated with an increase in body frame size at puberty in cattle. Anim Genet 42 : 650–655.

69. GudbjartssonDF, WaltersGB, ThorleifssonG, StefanssonH, HalldorssonBV, et al. (2008) Many sequence variants affecting diversity of adult human height. Nat Genet 40 : 609–615.

70. SoranzoN, RivadeneiraF, Chinappen-HorsleyU, MalkinaI, RichardsJB, et al. (2009) Meta-analysis of genome-wide scans for human adult stature identifies novel loci and associations with measures of skeletal frame size. PLoS Genet 5: e1000445 doi:10.1371/journal.pgen.1000445.

71. WeedonMN, LangoH, LindgrenCM, WallaceC, EvansDM, et al. (2008) Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 40 : 575–583.

72. BrooksSA, Makvandi-NejadS, ChuE, AllenJJ, StreeterC, et al. (2010) Morphological variation in the horse: defining complex traits of body size and shape. Anim Genet 41 Suppl 2 : 159–165.

73. Makvandi-NejadS, HoffmanGE, AllenJJ, ChuE, GuE, et al. (2012) Four Loci explain 83% of size variation in the horse. PLoS ONE 7: e39929 doi:10.1371/journal.pone.0039929.

74. Signer-HaslerH, FluryC, HaaseB, BurgerD, SimianerH, et al. (2012) A genome-wide association study reveals loci influencing height and other conformation traits in horses. PLoS ONE 7: e37282 doi:10.1371/journal.pone.0037282.

75. BakerJ, LiuJP, RobertsonEJ, EfstratiadisA (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75 : 73–82.

76. LiuJP, BakerJ, PerkinsAS, RobertsonEJ, EfstratiadisA (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75 : 59–72.

77. OkadaY, KamataniY, TakahashiA, MatsudaK, HosonoN, et al. (2010) A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. Hum Mol Genet 19 : 2303–2312.

78. WoodsKA, Camacho-HubnerC, BarterD, ClarkAJ, SavageMO (1997) Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature. Acta Paediatr Suppl 423 : 39–45.

79. PryceJE, HayesBJ, BolormaaS, GoddardME (2011) Polymorphic regions affecting human height also control stature in cattle. Genetics 187 : 981–984.

80. VisscherPM (2008) Sizing up human height variation. Nat Genet 40 : 489–490.

81. WeedonMN, LettreG, FreathyRM, LindgrenCM, VoightBF, et al. (2007) A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat Genet 39 : 1245–1250.

82. MonzenK, ItoY, NaitoAT, KasaiH, HiroiY, et al. (2008) A crucial role of a high mobility group protein HMGA2 in cardiogenesis. Nat Cell Biol 10 : 567–574.

83. MauranoMT, HumberR, RynesE, ThurmanRE, HaugenE, et al. (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337 : 1190–1195.

84. BernsteinBE, BirneyE, DunhamI, GreenED, GunterC, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489 : 57–74.

85. VernotB, StergachisAB, MauranoMT, VierstrJ, NephS, et al. (2012) Personal and population genomics of human regulatory variation. Genome Res 22 : 1689–1697.

86. PurcellS, NealeB, Tood-BrownK, ThomasL, FerreiraMAR, et al. (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Amer J Hum Genet 81 : 559–575.

87. LettreG, JacksonAU, GiegerC, SchumacherFR, BerndtSI, et al. (2008) Identification of ten loci associated with height highlights new biological pahtways in human growth. Nat Genet 40 : 584–591.

88. ScheetP, StephensM (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78 : 629–644.

89. Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S, editors. Bioinformatics Methods and Protocols: Methods in Molecular Biology. Humana Press, Totowa, NJ, pp 365–386.