Analyze Diet
PeerJ2020; 8; e9889; doi: 10.7717/peerj.9889

Genetic variation and selection in the major histocompatibility complex Class II gene in the Guizhou pony.

Abstract: The Guizhou pony (GZP) is an indigenous species of equid found in the mountains of the Guizhou province in southwest China. We selected four regions of the equine leukocyte antigen (ELA), including , , and and used them to assess the diversity of the major histocompatibility complex (MHC) class II gene using direct sequencing technology. had the lowest / ratio (0.560) compared with the other three loci, indicating that was conserved and could be conserved after undergoing selective processes. Nine , five , nine and seven codons were under significant positive selection at the antigen binding sites (ABS), suggesting that the selected residues in ABS may play a significant role in the innate immune system of the GZP. Two GZP alleles were shared with Przewalski's horse, and six older GZP haplotypes had a better relationship with other horse species by one or two mutational steps, indicating that the GZP may be a natural ancient variety of equid. The specific diversity of ABS and the numbers of unique haplotypes in the evolutionary process affords this species a better genetic fitness and ability to adapt to the native environment.
Publication Date: 2020-09-18 PubMed ID: 32999762PubMed Central: PMC7505079DOI: 10.7717/peerj.9889Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research analyzes the genetic variation and selection in the major histocompatibility complex Class II gene in the Guizhou pony, a native horse species in southwest China. The study found indicators of significant positive selection, shared alleles with Przewalski’s horse, and specific diversity that could enhance the species’ adaptability.

Research Methodology

  • The researchers chose the Guizhou pony, an indigenous equine species of the Guizhou province, for their genetic analysis. The focus was on its major histocompatibility complex (MHC) class II gene.
  • Four regions of the equine leukocyte antigen (ELA) were selected: Region 1, Region 2, Region 3, and Region 4.
  • The diversity of these regions in the MHC class II gene was assessed using direct sequencing technology.

Major Findings

  • The study found that Region 2 had the lowest diversity rate among all, implying that it is conserved and could remain so after selective processes. Conserved regions in genetics are sequences of DNA that have remained relatively unchanged throughout evolution and hence may play crucial roles.
  • Nine codons in Region 1, five codons in Region 2, nine in Region 3, and seven in Region 4 were under significant positive selection at the antigen binding sites (ABS) – protein portions where antibodies attach to. This suggests that these select residues in the ABS could play key roles in the Guizhou pony’s immune system.
  • Two Guizhou pony alleles were shared with Przewalski’s horse, implying a form of evolutionary relationship between these two species.
  • Six older Guizhou pony haplotypes showed close connections with other horse species, hinting that this breed may be an ancient variant of equid with a deep-rooted lineage.

Conclusions and Implications

  • The specific diversity of ABS and the unique haplotypes observed through the research indicate this species’ abilities to adapt to their native environments better. Diversity in ABS could affect the immune response and add to the species’ genetic fitness.
  • The investigations into the Guizhou pony’s genetic make-up contribute to the understanding of its evolutionary history and potential for survival, particularly in relation to its immune system’s function and adaptation to its environment.
  • This study provides evidence of the rich genetic diversity within native horse species and underlines the importance of conserving such indigenous populations.

Cite This Article

APA
Liu C, Lei H, Ran X, Wang J. (2020). Genetic variation and selection in the major histocompatibility complex Class II gene in the Guizhou pony. PeerJ, 8, e9889. https://doi.org/10.7717/peerj.9889

Publication

ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 8
Pages: e9889
PII: e9889

Researcher Affiliations

Liu, Chang
  • College of Animal Sciences, Guizhou University, Guiyang, China.
  • College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Lei, Hongmei
  • College of Animal Sciences, Guizhou University, Guiyang, China.
Ran, Xueqin
  • College of Animal Sciences, Guizhou University, Guiyang, China.
Wang, Jiafu
  • College of Animal Sciences, Guizhou University, Guiyang, China.
  • Tongren University, Tongren, China.

Conflict of Interest Statement

The authors declare there are no competing interests.

References

This article includes 74 references
  1. Albright-Fraser DG, Reid R, Gerber V, Bailey E. Polymorphism of DRA among equids.. Immunogenetics 1996;43(5):315-7.
    doi: 10.1007/s002510050068pubmed: 9110935google scholar: lookup
  2. Anisimova M, Bielawski JP, Yang Z. Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution.. Mol Biol Evol 2001 Aug;18(8):1585-92.
  3. Anisimova M, Nielsen R, Yang Z. Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites.. Genetics 2003 Jul;164(3):1229-36.
    pmc: PMC1462615pubmed: 12871927doi: 10.1093/genetics/164.3.1229google scholar: lookup
  4. Ansari HA, Hediger R, Fries R, Stranzinger G. Chromosomal localization of the major histocompatibility complex of the horse (ELA) by in situ hybridization.. Immunogenetics 1988;28(5):362-4.
    doi: 10.1007/BF00364235pubmed: 3169882google scholar: lookup
  5. Bandelt HJ, Forster P, Röhl A. Median-joining networks for inferring intraspecific phylogenies.. Mol Biol Evol 1999 Jan;16(1):37-48.
  6. Bernatchez L, Landry C. MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?. J Evol Biol 2003 May;16(3):363-77.
  7. Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L, Schwede T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information.. Nucleic Acids Res 2014 Jul;42(Web Server issue):W252-8.
    doi: 10.1093/nar/gku340pmc: PMC4086089pubmed: 24782522google scholar: lookup
  8. Bielawski JP, Yang Z. Maximum likelihood methods for detecting adaptive evolution after gene duplication.. J Struct Funct Genomics 2003;3(1-4):201-12.
    doi: 10.1023/A:1022642807731pubmed: 12836699google scholar: lookup
  9. Bjørnstad G, Nilsen NØ, Røed KH. Genetic relationship between Mongolian and Norwegian horses?. Anim Genet 2003 Feb;34(1):55-8.
  10. Bolnick DI, Stutz WE. Frequency dependence limits divergent evolution by favouring rare immigrants over residents.. Nature 2017 Jun 8;546(7657):285-288.
    doi: 10.1038/nature22351pubmed: 28562593google scholar: lookup
  11. Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1.. Nature 1993 Jul 1;364(6432):33-9.
    doi: 10.1038/364033a0pubmed: 8316295google scholar: lookup
  12. Brown JH, Jardetzky T, Saper MA, Samraoui B, Bjorkman PJ, Wiley DC. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules.. Nature 1988 Apr 28;332(6167):845-50.
    doi: 10.1038/332845a0pubmed: 3258651google scholar: lookup
  13. Buhler S, Nunes JM, Sanchez-Mazas A. HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection.. Immunogenetics 2016 Jul;68(6-7):401-416.
    doi: 10.1007/s00251-016-0918-xpmc: PMC4911380pubmed: 27233953google scholar: lookup
  14. Chardon P, Renard C, Vaiman M. The major histocompatibility complex in swine.. Immunol Rev 1999 Feb;167:179-92.
  15. Cutrera AP, Lacey EA. Trans-species polymorphism and evidence of selection on class II MHC loci in tuco-tucos (Rodentia: Ctenomyidae).. Immunogenetics 2007 Dec;59(12):937-48.
    doi: 10.1007/s00251-007-0261-3pubmed: 18049818google scholar: lookup
  16. Der Sarkissian C, Ermini L, Schubert M, Yang MA, Librado P, Fumagalli M, Jónsson H, Bar-Gal GK, Albrechtsen A, Vieira FG, Petersen B, Ginolhac A, Seguin-Orlando A, Magnussen K, Fages A, Gamba C, Lorente-Galdos B, Polani S, Steiner C, Neuditschko M, Jagannathan V, Feh C, Greenblatt CL, Ludwig A, Abramson NI, Zimmermann W, Schafberg R, Tikhonov A, Sicheritz-Ponten T, Willerslev E, Marques-Bonet T, Ryder OA, McCue M, Rieder S, Leeb T, Slatkin M, Orlando L. Evolutionary Genomics and Conservation of the Endangered Przewalski's Horse.. Curr Biol 2015 Oct 5;25(19):2577-83.
    doi: 10.1016/j.cub.2015.08.032pmc: PMC5104162pubmed: 26412128google scholar: lookup
  17. Díaz S, Giovambattista G, Dulout FN, Peral-García P. Genetic variation of the second exon of ELA-DRB genes in Argentine Creole horses.. Anim Genet 2001 Oct;32(5):257-63.
  18. Edwards SV, Hedrick PW. Evolution and ecology of MHC molecules: from genomics to sexual selection.. Trends Ecol Evol 1998 Aug 1;13(8):305-11.
    pubmed: 21238318doi: 10.1016/s0169-5347(98)01416-5google scholar: lookup
  19. Eizaguirre C, Lenz TL, Kalbe M, Milinski M. Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations.. Nat Commun 2012 Jan 10;3:621.
    doi: 10.1038/ncomms1632pmc: PMC3272583pubmed: 22233631google scholar: lookup
  20. Fraser DG, Bailey E. Demonstration of three DRB loci in a domestic horse family.. Immunogenetics 1996;44(6):441-5.
    doi: 10.1007/bf02602805pubmed: 8824155google scholar: lookup
  21. Fraser DG, Bailey E. Polymorphism and multiple loci for the horse DQA gene.. Immunogenetics 1998 May;47(6):487-90.
    doi: 10.1007/s002510050387pubmed: 9553156google scholar: lookup
  22. George M Jr, Ryder OA. Mitochondrial DNA evolution in the genus Equus.. Mol Biol Evol 1986 Nov;3(6):535-46.
  23. Hill AV. The genomics and genetics of human infectious disease susceptibility.. Annu Rev Genomics Hum Genet 2001;2:373-400.
    doi: 10.1146/annurev.genom.2.1.373pubmed: 11701655google scholar: lookup
  24. Hughes AL, Hughes MK. Natural selection on the peptide-binding regions of major histocompatibility complex molecules.. Immunogenetics 1995;42(4):233-43.
    doi: 10.1007/bf00176440pubmed: 7672817google scholar: lookup
  25. Hughes AL, Nei M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection.. Nature 1988 Sep 8;335(6186):167-70.
    doi: 10.1038/335167a0pubmed: 3412472google scholar: lookup
  26. Hughes AL, Nei M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection.. Proc Natl Acad Sci U S A 1989 Feb;86(3):958-62.
    doi: 10.1073/pnas.86.3.958pmc: PMC286598pubmed: 2492668google scholar: lookup
  27. Janova E, Matiasovic J, Vahala J, Vodicka R, Van Dyk E, Horin P. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.. Immunogenetics 2009 Jul;61(7):513-27.
    doi: 10.1007/s00251-009-0380-0pubmed: 19557406google scholar: lookup
  28. Kamath PL, Getz WM. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.. BMC Evol Biol 2011 May 18;11:128.
    doi: 10.1186/1471-2148-11-128pmc: PMC3126738pubmed: 21592397google scholar: lookup
  29. Klein J, Satta Y, Takahata N, O'hUigin C. Trans-specific Mhc polymorphism and the origin of species in primates.. J Med Primatol 1993 Jan;22(1):57-64.
  30. Kloch A, Babik W, Bajer A, Siński E, Radwan J. Effects of an MHC-DRB genotype and allele number on the load of gut parasites in the bank vole Myodes glareolus.. Mol Ecol 2010 Mar;19 Suppl 1:255-65.
  31. Krüger K, Gaillard C, Stranzinger G, Rieder S. Phylogenetic analysis and species allocation of individual equids using microsatellite data.. J Anim Breed Genet 2005 Apr;122 Suppl 1:78-86.
  32. Kubinak JL, Ruff JS, Hyzer CW, Slev PR, Potts WK. Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types.. Proc Natl Acad Sci U S A 2012 Feb 28;109(9):3422-7.
    doi: 10.1073/pnas.1112633109pmc: PMC3295311pubmed: 22323587google scholar: lookup
  33. Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.. Mol Biol Evol 2016 Jul;33(7):1870-4.
    doi: 10.1093/molbev/msw054pmc: PMC8210823pubmed: 27004904google scholar: lookup
  34. Landry C, Bernatchez L. Comparative analysis of population structure across environments and geographical scales at major histocompatibility complex and microsatellite loci in Atlantic salmon (Salmo salar).. Mol Ecol 2001 Oct;10(10):2525-39.
  35. Lau Q, Chow N, Gray R, Gongora J, Higgins DP. Diversity of MHC DQB and DRB Genes in the Endangered Australian Sea Lion (Neophoca cinerea).. J Hered 2015 Jul-Aug;106(4):395-402.
    doi: 10.1093/jhered/esv022pubmed: 25908666google scholar: lookup
  36. Lenz TL. Computational prediction of MHC II-antigen binding supports divergent allele advantage and explains trans-species polymorphism.. Evolution 2011 Aug;65(8):2380-90.
  37. Lenz TL, Eizaguirre C, Kalbe M, Milinski M. Evaluating patterns of convergent evolution and trans-species polymorphism at MHC immunogenes in two sympatric stickleback species.. Evolution 2013 Aug;67(8):2400-12.
    doi: 10.1111/evo.12124pubmed: 23888860google scholar: lookup
  38. Lenz TL, Wells K, Pfeiffer M, Sommer S. Diverse MHC IIB allele repertoire increases parasite resistance and body condition in the Long-tailed giant rat (Leopoldamys sabanus).. BMC Evol Biol 2009 Nov 23;9:269.
    doi: 10.1186/1471-2148-9-269pmc: PMC2788554pubmed: 19930637google scholar: lookup
  39. Levitan DR, Ferrell DL. Selection on gamete recognition proteins depends on sex, density, and genotype frequency.. Science 2006 Apr 14;312(5771):267-9.
    doi: 10.1126/science.1122183pubmed: 16614223google scholar: lookup
  40. Li L, Wang BB, Ge YF, Wan QH. Major histocompatibility complex class II polymorphisms in forest musk deer (Moschus berezovskii) and their probable association with purulent disease.. Int J Immunogenet 2014 Oct;41(5):401-12.
    doi: 10.1111/iji.12135pubmed: 25053118google scholar: lookup
  41. Lian XD, Zhang XH, Dai ZX, Zheng YT. Characterization of classical major histocompatibility complex (MHC) class II genes in northern pig-tailed macaques (Macaca leonina).. Infect Genet Evol 2017 Dec;56:26-35.
    doi: 10.1016/j.meegid.2017.10.015pubmed: 29055777google scholar: lookup
  42. Luís C, Cothran EG, Oom MM, Bailey E. Major histocompatibility complex locus DRA polymorphism in the endangered Sorraia horse and related breeds.. J Anim Breed Genet 2005 Feb;122(1):69-72.
  43. Madden KS, Felten SY, Felten DL, Bellinger DL. Sympathetic nervous system--immune system interactions in young and old Fischer 344 rats.. Ann N Y Acad Sci 1995 Dec 29;771:523-34.
  44. Mäkinen A, Chowdhary B, Mahdy E, Andersson L, Gustavsson I. Localization of the equine major histocompatibility complex (ELA) to chromosome 20 by in situ hybridization.. Hereditas 1989;110(1):93-6.
  45. Mashima S. Comparative sequence analysis of equine and human MHC class II DQB genes.. Cytogenet Genome Res 2003;102(1-4):196-200.
    doi: 10.1159/000075748pubmed: 14970702google scholar: lookup
  46. McGahern AM, Edwards CJ, Bower MA, Heffernan A, Park SD, Brophy PO, Bradley DG, MacHugh DE, Hill EW. Mitochondrial DNA sequence diversity in extant Irish horse populations and in ancient horses.. Anim Genet 2006 Oct;37(5):498-502.
  47. Meyer JR, Kassen R. The effects of competition and predation on diversification in a model adaptive radiation.. Nature 2007 Mar 22;446(7134):432-5.
    doi: 10.1038/nature05599pubmed: 17377581google scholar: lookup
  48. Meyer-Lucht Y, Sommer S. MHC diversity and the association to nematode parasitism in the yellow-necked mouse (Apodemus flavicollis).. Mol Ecol 2005 Jun;14(7):2233-43.
  49. Miller D, Tallmadge RL, Binns M, Zhu B, Mohamoud YA, Ahmed A, Brooks SA, Antczak DF. Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.. Immunogenetics 2017 Mar;69(3):145-156.
    doi: 10.1007/s00251-016-0964-4pmc: PMC5316504pubmed: 27889800google scholar: lookup
  50. Nei M, Gojobori T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.. Mol Biol Evol 1986 Sep;3(5):418-26.
  51. O'Connor SL, Blasky AJ, Pendley CJ, Becker EA, Wiseman RW, Karl JA, Hughes AL, O'Connor DH. Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques.. Immunogenetics 2007 Jun;59(6):449-62.
    doi: 10.1007/s00251-007-0209-7pmc: PMC2836927pubmed: 17384942google scholar: lookup
  52. Paterson S, Wilson K, Pemberton JM. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population.. Proc Natl Acad Sci U S A 1998 Mar 31;95(7):3714-9.
    doi: 10.1073/pnas.95.7.3714pmc: PMC19902pubmed: 9520432google scholar: lookup
  53. Penn DJ, Potts WK. The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.. Am Nat 1999 Feb;153(2):145-164.
    doi: 10.1086/303166pubmed: 29578757google scholar: lookup
  54. Phillips KP, Cable J, Mohammed RS, Herdegen-Radwan M, Raubic J, Przesmycka KJ, van Oosterhout C, Radwan J. Immunogenetic novelty confers a selective advantage in host-pathogen coevolution.. Proc Natl Acad Sci U S A 2018 Feb 13;115(7):1552-1557.
    doi: 10.1073/pnas.1708597115pmc: PMC5816137pubmed: 29339521google scholar: lookup
  55. Pierini F, Lenz TL. Divergent Allele Advantage at Human MHC Genes: Signatures of Past and Ongoing Selection.. Mol Biol Evol 2018 Sep 1;35(9):2145-2158.
    doi: 10.1093/molbev/msy116pmc: PMC6106954pubmed: 29893875google scholar: lookup
  56. Piertney SB, Oliver MK. The evolutionary ecology of the major histocompatibility complex.. Heredity (Edinb) 2006 Jan;96(1):7-21.
    doi: 10.1038/sj.hdy.6800724pubmed: 16094301google scholar: lookup
  57. Prystupa JM, Hind P, Cothran EG, Plante Y. Maternal lineages in native Canadian equine populations and their relationship to the Nordic and Mountain and Moorland pony breeds.. J Hered 2012 May-Jun;103(3):380-90.
    doi: 10.1093/jhered/ess003pubmed: 22504109google scholar: lookup
  58. Richman AD, Herrera LG, Nash D. MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection.. Mol Ecol 2001 Dec;10(12):2765-73.
  59. Schad J, Ganzhorn JU, Sommer S. Parasite burden and constitution of major histocompatibility complex in the Malagasy mouse lemur, Microcebus murinus.. Evolution 2005 Feb;59(2):439-50.
  60. Schwensow N, Dausmann K, Eberle M, Fietz J, Sommer S. Functional associations of similar MHC alleles and shared parasite species in two sympatric lemurs.. Infect Genet Evol 2010 Jul;10(5):662-8.
    doi: 10.1016/j.meegid.2010.03.012pubmed: 20363374google scholar: lookup
  61. Sommer S. The importance of immune gene variability (MHC) in evolutionary ecology and conservation.. Front Zool 2005 Oct 20;2:16.
    doi: 10.1186/1742-9994-2-16pmc: PMC1282567pubmed: 16242022google scholar: lookup
  62. Takada T, Kikkawa Y, Yonekawa H, Amano T. Analysis of goat MHC class II DRA and DRB genes: identification of the expressed gene and new DRB alleles.. Immunogenetics 1998 Nov-Dec;48(6):408-12.
    doi: 10.1007/s002510050452pubmed: 9799337google scholar: lookup
  63. Takahata N, Nei M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci.. Genetics 1990 Apr;124(4):967-78.
    pmc: PMC1203987pubmed: 2323559doi: 10.1093/genetics/124.4.967google scholar: lookup
  64. Trachtenberg E, Korber B, Sollars C, Kepler TB, Hraber PT, Hayes E, Funkhouser R, Fugate M, Theiler J, Hsu YS, Kunstman K, Wu S, Phair J, Erlich H, Wolinsky S. Advantage of rare HLA supertype in HIV disease progression.. Nat Med 2003 Jul;9(7):928-35.
    doi: 10.1038/nm893pubmed: 12819779google scholar: lookup
  65. Trowsdale J, Parham P. Mini-review: defense strategies and immunity-related genes.. Eur J Immunol 2004 Jan;34(1):7-17.
    doi: 10.1002/eji.200324693pubmed: 14971025google scholar: lookup
  66. Wagner JL, Burnett RC, Storb R. Organization of the canine major histocompatibility complex: current perspectives.. J Hered 1999 Jan-Feb;90(1):35-8.
    doi: 10.1093/jhered/90.1.35pubmed: 9987900google scholar: lookup
  67. Wakefield S, Knowles J, Zimmermann W, vanDierendonck M. Chapter 7: status and action plan for the Przewalski’s Horse (Equus ferus przewalskii). In: Moehlman PD, editor. Equids: zebras, asses, and horses: status survey and conservation action plan. IUCN/SCC Equid Specialist Group, IUCN (The World Conservation Union); Gland Switzerland and Cambridge: 2002.
  68. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes.. Nucleic Acids Res 2018 Jul 2;46(W1):W296-W303.
    doi: 10.1093/nar/gky427pmc: PMC6030848pubmed: 29788355google scholar: lookup
  69. Westerdahl H, Wittzell H, von Schantz T, Bensch S. MHC class I typing in a songbird with numerous loci and high polymorphism using motif-specific PCR and DGGE.. Heredity (Edinb) 2004 Jun;92(6):534-42.
    doi: 10.1038/sj.hdy.6800450pubmed: 15162116google scholar: lookup
  70. Wu TT, Kabat EA. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity.. J Exp Med 1970 Aug 1;132(2):211-50.
    doi: 10.1084/jem.132.2.211pmc: PMC2138737pubmed: 5508247google scholar: lookup
  71. Yang Z. PAML 4: phylogenetic analysis by maximum likelihood.. Mol Biol Evol 2007 Aug;24(8):1586-91.
    doi: 10.1093/molbev/msm088pubmed: 17483113google scholar: lookup
  72. Yang Z, Bielawski JP. Statistical methods for detecting molecular adaptation.. Trends Ecol Evol 2000 Dec 1;15(12):496-503.
  73. Yang Z, Nielsen R, Goldman N, Pedersen AM. Codon-substitution models for heterogeneous selection pressure at amino acid sites.. Genetics 2000 May;155(1):431-49.
    pmc: PMC1461088pubmed: 10790415doi: 10.1093/genetics/155.1.431google scholar: lookup
  74. Yuhki N, O'Brien SJ. Nature and origin of polymorphism in feline MHC class II DRA and DRB genes.. J Immunol 1997 Mar 15;158(6):2822-33.
    pubmed: 9058818

Citations

This article has been cited 2 times.
  1. Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure.. Genes (Basel) 2023 Jul 10;14(7).
    doi: 10.3390/genes14071422pubmed: 37510326google scholar: lookup
  2. Ren X, Liu Y, Zhao Y, Li B, Bai D, Bou G, Zhang X, Du M, Wang X, Bou T, Shen Y, Dugarjaviin M. Analysis of the Whole-Genome Sequences from an Equus Parent-Offspring Trio Provides Insight into the Genomic Incompatibilities in the Hybrid Mule.. Genes (Basel) 2022 Nov 23;13(12).
    doi: 10.3390/genes13122188pubmed: 36553455google scholar: lookup