Patterns of nucleotide substitutions inferred from the phylogenies of the class I major histocompatibility complex genes

Tadashi Imanishi*, Takashi Gojobori

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Patterns of nucleotide substitutions in human major histocompatibility complex (MHC) class I genes were estimated by using phylogenetic trees of DNA sequences. The pattern is defined as a set of 12 parameters, each of which represents the relative frequency of substitutions from a particular nucleotide to another. The pattern at the antigen recognition sites (ARS) in functional MHC genes was remarkably different from that at the remaining coding region (non-ARS). In particular, the proportion of transitions among all the nucleotide substitutions (Ps) was extremely low at the third codon positions of ARS. In the HLA-A genes, Ps at the third codon positions was only 6% in ARS, whereas it was 69% in non-ARS. In HLA-B, the corresponding values were 30% in ARS and 80% in non-ARS, respectively. On the other hand, Ps in a class I pseudogene (HLA-H) was 57%, which was in good agreement with Ps in other pseudogenes. Because pseudogenes are selectively neutral, the pattern in pseudogenes is regarded as the pattern of spontaneous substitution mutations. In general, the pattern in functional genes that are subject to selective forces deviates from the pattern in pseudogenes. At the third codon positions in coding regions, transitions scarcely cause amino acid replacements, whereas about half of transversions do cause replacements. Accordingly, Ps at the third codon positions decreases if amino acid replacements are accelerated by natural selection but increases if amino acids are conserved by functional constraint. Our observations imply that the ARS region is subject to natural selection favoring amino acid replacements, whereas the non-ARS region is subject to functional constraint.

Original languageEnglish (US)
Pages (from-to)196-204
Number of pages9
JournalJournal of Molecular Evolution
Issue number3
StatePublished - Sep 1992
Externally publishedYes


  • Antigen recognition site (ARS)
  • Functional constraint
  • HLA
  • Major histocompatibility complex (MHC)
  • Natural selection
  • Neutrality
  • Patterns of nucleotide substitutions
  • Pseudogene

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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