Sexual preference of apparent gene conversion events in MHC genes of mice

Abstract

Polymorphisms exist at many genetic loci. At some loci, however, polymorphism is so high that tens and even hundreds of different alleles coexist in the population. Two such highly polymorphic systems are the immunoglobulin genes and the vertebrate major histocompatibility loci. The origin and maintenance of highly polymorphic loci remain open to debate but it seems likely that special mechanisms contribute to their variability and that their polymorphism serves important biological roles. The high degree of polymorphism at the H–2 class I major histocompatibility locus of the mouse has been documented by both tissue transplantation and serological methods1. More recently, molecular cloning and DNA sequencing of some of the class I genes has shown that most of the sequence variability is concentrated in the first two domains and is often found in clustered regions within them2–4. In addition, several groups have suggested that gene conversion events among the many class I genes may contribute to H–2 polymorphism5,6; such events would have to occur during meiosis to produce heritable alterations. The strongest evidence for gene conversion comes from sequence analysis of mutant class I H–2 alleles where concerted changes at adjoining sites in DNA imply gene conversion by distant but closely related loci5,6. We report here an analysis of these mutants indicating that the chromosomes containing loci that have experienced gene conversion originated from females. These data suggest a striking preference for mammalian meiotic gene conversion events during female rather than male gametogenesis.