Open AccessThe synonymous substitution rate of the major histocompatibility complex loci in primates.
Author(s) -
Yoko Satta,
Colm Ó'hUigín,
Naoyuki Takahata,
Jan Klein
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.16.7480
Subject(s) - major histocompatibility complex , biology , genetics , mutation rate , divergence (linguistics) , allele , substitution (logic) , synonymous substitution , evolutionary biology , gene , genome , linguistics , philosophy , codon usage bias , computer science , programming language
Because the divergence of many allelic lineages at the major histocompatibility complex (MHC) loci predates species divergence, standard methods of calculating synonymous substitution rates are not applicable to this system. We used three alternative methods of rate estimation: one based on the minimum number of substitutions (Dm), another on the nucleotide difference (Dxy), and the third on the net nucleotide difference (Dn). We applied these methods to the protein-encoding sequences of primate MHC class I (A, B, and C) and class II (DRB1) genes. To determine the reliability of the different estimates, we carried out computer simulation. The distribution of the estimates based on Dxy or Dn is generally much broader than that based on Dm. More importantly, the Dm-based method nearly always has the highest probability of recovering true rates, provided that Dm is not smaller than 5. Because of its desirable statistical properties, we used the Dm-based method to estimate the rate of synonymous substitutions. The rate is 1.37 +/- 0.61 for A, 1.84 +/- 0.40 for B, 3.87 +/- 1.05 for C, and 1.18 +/- 0.36 for DRB1 loci, always per site per 10(9) years. Hence despite the extraordinary polymorphism, the mutation rate at the primate MHC loci is no higher than that of other loci.