Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains

Abstract

Mitotic recombination occurs with high frequency in humans^1,2 and mice³. It leads to loss of heterozygosity (LOH) at important gene loci and can cause disease^4,5,6,7. However, the genetic modulators of mitotic recombination are not well understood. As recombination depends on a high level of nucleotide sequence homology^8,9,10,11,12, we postulate that the frequency of somatic variants derived from mitotic recombination should be diminished in progeny from crosses between strains of mice in which nucleotide sequences have diverged. Here we report that mitotic recombination is suppressed, to various degrees in different tissues, in hybrids of distantly related mouse strains. Reintroduction of greater chromosomal homology by backcrossing restores mitotic recombination in offspring. Thus, chromosomal divergence inhibits mitotic recombination and, consequently, may act as a modifier of cancer susceptibility by limiting the rate of LOH. The suppression of mitotic recombination in some F₁ hybrids in which meiotic recombination persists indicates that these processes are differentially affected by chromosomal divergence.