主要组织相容性复合体(Major histocompatibility complex, MHC)对许多疾病的易感性和抵抗力起着重要的作用。为了解藏酋猴(Macaca thibetana)的MHC基因遗传背景, 以促进藏酋猴遗传资源的保护及其在生物医学研究中的应用, 文章采用PCR扩增和克隆测序等方法对来自四川地区的70个藏酋猴样品的Mhc-DPB1基因exon 2进行了检测和分析。首次在藏酋猴中获得了18个DPB1等位基因(Math-DPB1), 其中1个为假基因(Math- DPB1*01:06N)。18个等位基因中, Math-DPB1*06:01:01 (67.14%) 的阳性检出率最高, 其次为Math-DPB1*01:03:01 (37.14%)、Math-DPB1*09:02 (25.71%)和Math-DPB1*22:01 (15.71%)。氨基酸序列比对发现, 藏酋猴Math-DPB1等位基因编码的氨基酸序列中, 有5个氨基酸残基变异位点表现出物种特异性。不同物种来源的DPB1等位基因系统发生树表明, 藏酋猴、猕猴(Macaca mulatta)和食蟹猴(Macaca fascicu-laris)的DPB1等位基因不是以物种特异性方式聚类, 而是种间混聚在一起, 并显示出明显的跨物种多态性(Trans-species polymorphism)。选择性检验表明, 平衡选择(Balancing selection)在维持Math-DPB1基因的多态性中起着重要的作用。
Major histocompatibility complex (MHC) molecules play an important role in the susceptibility and/or resistance to many diseases. To gain an insight into the MHC background of the Tibetan macaques (Macaca thibetana), and thereby facilitate their protection and application in biomedical research, the second exon of the Mhc-DPB1 genes from 70 Tibetan macaques in Sichuan Province were characterized by PCR, cloning, sequencing, and statistical analysis. A total of 18 Mhc-DPB1 alleles were identified from Tibetan macaques, of which one (Math-DPB1*01:06N) was a pseudogene. Math-DPB1*06:01:01 (67.14%) was the most frequent allele in all the 18 alleles detected, followed by Math-DPB1* 01:03:01 (37.14%), Math-DPB1*09:02 (25.71%), and Math-DPB1*22:01 (15.71%). The alignment of putative amino acid sequences of the 18 Math-DPB1 alleles showed that 5 variable sites were species-specific to Tibetan macaques. A phylogenetic tree constructed using DPB1 alleles in difference species demonstrated that the alleles for Math-DPB1, Mamu-DPB1, and Mafa-DPB1 tended to mix together, rather than cluster into a separate branch in a species-specific fashion, and the Trans-species polymorphism was also observed in the phylogenetic tree. Selection analysis revealed that balancing selection may play an important role in maintaining the polymorphism of Math-DPB1 genes.
[1] 蒋学龙, 王应祥, 王歧山. 藏酋猴的分类与分布. 动物学研究, 1996, 17(4): 361-369.
[2] 王红星, 姚方, 周亮, 钟浩, 许跃忠. 藏酋猴人工繁育研究概况. 中国科技成果, 2009, 10(23): 38-40.
[3] Liu G, Zeng T, Yu WH, Yan NH, Wang HX, Cai SP, Pang IH, Liu XY. Characterization of intraocular pressure responses of the Tibetan monkey (Macaca thibetana). Mol Vis, 2011, 17: 1405-1413.
[4] Boyson JE, Shufflebotham C, Cadavid LF, Urvater JA, Knapp LA, Hughes AL, Watkins DI. The MHC class I genes of the rhesus monkey. Different evolutionary histories of MHC class I and II genes in primates. J Immunol, 1996, 156(12): 4656-4665.
[5] Cresswell P. Antigen processing and presentation. Immunol Rev, 2005, 207(1): 5-7.
[6] Srisapoome P, Ohira T, Hirono I, Aoki T. Cloning, characterization and expression of cDNA containing major his-tocompatibility complex classⅠ, Ⅱα and Ⅱβ genes of Japanese flounder Paralichtys olivaceus. Fisheries Sci, 2004, 70(2): 264-276.
[7] Kjøglum S, Larsen S, Bakke HG, Grimholt U. How specific MHC classⅠ and classⅡ combinations affect disease resistance against infectious salmon anaemia in At-lantic salmon (Salmo salar). Fish Shellfish Immunol, 2006, 21(4): 431-441.
[8] Piertney SB, Oliver MK. The evolutionary ecology of the major histocompatibility complex. Heredity, 2006, 96(1): 7-21.
[9] McCanlies EC, Ensey JS, Schuler CR, Kreiss K, Weston A. The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization. Am J Ind Med, 2004, 46(2): 95-103.
[10] Slierendregt BL, Otting N, Kenter M, Bontrop RE. Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta). Immunogenetics, 1995, 41(1): 29-37.
[11] Arnold ML, Pei R, Spriewald B, Wassmuth R. Anti-HLA classⅡ antibodies in kidney retransplant patients. Tissue Antigens, 2005, 65(4): 370-378.
[12] Doxiadis GG, Otting N, de Groot NG, Bontrop RE. Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies. Immunol Rev, 2001, 183(1): 76-85.
[13] Ellis SA, Bontrop RE, Antczak DF, Ballingall K, Davies CJ, Kaufman J, Kennedy LJ, Robinson J, Smith DM, Stear MJ, Stet RJM, Waller MJ, Walter L, Marsh SGE. ISAG/ IUIS-VIC comparative MHC nomenclature committee re-port, 2005. Immunogenetics, 2006, 57(12): 953-958.
[14] Yang ZH. PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Bio-sci, 1997, 13(5): 555-556.
[15] Yang ZH. PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol, 2007, 24(8): 1586-1591.
[16] Yang ZH, Nielsen R, Goldman N, Pedersen AMK. Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics, 2000, 155(1): 431-449.
[17] Yang ZH, Wong WSW, Nielsen R. Bayes Empirical Bayes inference of amino acid sites under positive selection. Mol Biol Evol, 2005, 22(4): 1107-1118.
[18] 徐怀亮, 汪宴廷, 程安春, 姚永芳, 倪庆永, 曾文, 毕风均, 杨泽霞, 陈孝跃. 猕猴Mhc-DPB1基因外显子2多态性研究. 遗传, 2010, 32(6): 588-598.
[19] Otting N, Doxiadis GGM, Versluis L, de Groota NG, An-holts J, Verduin W, Rozemuller E, Claas F, Tilanusb MGJ, Bontrop RE. Characterization and distribution of Mhc- DPB1 alleles in chimpanzee and rhesus macaque populations. Hum Immunol, 1998, 59(10): 656-664.
[20] Marsh SGE, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Geraghty DE, Hansen JA, Hurley CK, Mach B, Mayr WR, Parham P, Petersdorf EW, Sasazuki T, Schreuder GM Th, Strominger JL, Svejgaard A, Terasaki PI, Trowsdale J. Nomenclature for factors of the HLA system, 2004. Hum Immunol, 2005, 66(5): 571-636.
[21] O'Connor SL, Blasky AJ, Pendley CJ, Becker EA, Wise-man RW, Karl JA, Hughes AL, O’Connor DH. Compre-hensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques. Immuno
