Journal of Molecular Evolution

, Volume 61, Issue 4, pp 531–541

Inter- and Intralocus Recombination Drive MHC Class IIB Gene Diversification in a Teleost, the Three-Spined Stickleback Gasterosteus aculeatus


DOI: 10.1007/s00239-004-0340-0

Cite this article as:
Reusch, T.B. & Langefors, Å. J Mol Evol (2005) 61: 531. doi:10.1007/s00239-004-0340-0


The mutational mechanism underlying the striking diversity in MHC (major histocompatibility complex) genes in vertebrates is still controversial. In order to evaluate the role of inter- and intragenic recombination in MHC gene diversification, we examined patterns of nucleotide polymorphism across an exon/intron boundary in a sample of 31 MHC class IIB sequences of three-spined stickleback (Gasterosteus aculeatus). MHC class IIB genes of G. aculeatus were previously shown to be under diversifying (positive) selection in mate choice and pathogen selection experiments. Based on recoding of alignment gaps, complete intron 2 sequences were grouped into three clusters using maximum-parsimony analysis. Two of these groups had >90% bootstrap support and were tentatively assigned single locus status. Intron nucleotide diversity within and among loci was low (p-distance within and among groups = 0.016 and 0.019, respectively) and fourfold lower than the rate of silent mutations in exon 2, suggesting that noncoding regions are homogenized by frequent interlocus recombination. A substitution analysis using GENECONV revealed as many intergenic conversion events as intragenic ones. Recombination between loci may explain the occurrence of sequence variants that are particularly divergent, as is the case in three-spined stickleback, with nucleotide diversity attaining dN = 0.39 (peptide-binding residues only). For both MHC class II loci we also estimated the amount of intragenic recombination as population rate (4Ner) under the coalescent and found it to be approximately three times higher compared to point mutations (Watterson estimate per gene, 4Neμ). Nonindependence of molecular evolution across loci and frequent recombination suggest that MHC class II genes of bony fish may follow different evolutionary dynamics than those of mammals. Our finding of widespread recombination suggests that phylogenies of MHC genes should not be based on coding segments but rather on noncoding introns.


Diversifying selectionGene conversionMajor histocompatibility complexMHC class IIRecombinationSequence diversityThree-spined stickleback

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Evolutionary EcologyMax-Planck-Institut für LimnologieGermany
  2. 2.Department of Animal EcologyEcology Building, Lund UniversitySweden