title: Current perspectives on the intensity of natural selection of MHC loci.
abstract: Polymorphism of genes in the major histocompatibility complex (MHC) is believed to be maintained by balancing selection. However, direct evidence of selection has proven difficult to demonstrate. In 1994, Satta and colleagues estimated the selection intensity of the human MHC (human leukocyte antigen (HLA)) loci; however, at that time the number of HLA sequences was limited. By comparing five different methods, this study demonstrated the best way to calculate the selection coefficient, through a computer simulation study. Since the study, many HLA nucleotide sequences have been made available. Our new analysis takes advantage of these newly available sequences and compares new estimates with those of the previous study. Generally, our new results are consistent with those of the 1994 study. Our results show that, even after 20 years of exhaustive sequencing of human HLA, the number of dominant HLA alleles, on which our original estimate of selection intensity depended, appears to be conserved. Indeed, according to the frequency distribution for each HLA allele, most sequences in the database were minor or private alleles; therefore, we conclude that the selection intensities of HLA loci are at most 4.4 % even though the HLA is the prominent example on which the natural selection has been operating.
authors.affiliation: Department of Evolutionary Studies of Biosystems, The Graduate University for Advanced Studies (SOKENDAI), Shonan Village, Hayama, Kanagawa, Japan. hyasukou@proof.ocn.ne.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yasukochi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Satta
mesh_terms: D000483:Alleles; D003198:Computer Simulation; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D012641:Selection, Genetic / Q000235:genetics*
chemical_list: D006680:HLA Antigens
references.citation: Annu Rev Genet. 1998;32:415-35
references.pmid: 9928486
references.citation: Genetics. 1992 Apr;130(4):925-38
references.pmid: 1582567
references.citation: Science. 2011 Oct 7;334(6052):89-94
references.pmid: 21868630
references.citation: J Mol Evol. 1996 Jun;42(6):648-57
references.pmid: 8662017
references.citation: Annu Rev Genet. 2007;41:281-304
references.pmid: 18076327
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7184-8
references.pmid: 8041766
references.citation: Genetics. 1964 Apr;49:725-38
references.pmid: 14156929
references.citation: Nature. 1988 Sep 8;335(6186):167-70
references.pmid: 3412472
references.citation: Hum Immunol. 1987 Jul;19(3):155-62
references.pmid: 3305436
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D1171-6
references.pmid: 21071412
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3708-13
references.pmid: 9520431
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2419-23
references.pmid: 2320564
references.citation: Genetics. 1990 Apr;124(4):967-78
references.pmid: 2323559
references.citation: Proc Natl Acad Sci U S A. 1989 Feb;86(3):958-62
references.pmid: 2492668
references.citation: Nature. 2013 Jan 10;493(7431):216-20
references.pmid: 23201682