Extensive additivity of gene expression differentiates subspecies of the house mouse.

We have studied different subspecies of the house mouse and their reciprocal F(1) hybrids to estimate the within-locus mode of inheritance for subspecies differences in gene expression in three tissues (brain, liver, and testis) of male mice. This study investigates the mode of inheritance in crosses at a larger taxonomic distance than has been previously systematically investigated. We found the vast majority of transcripts to be additively expressed with only a few transcripts showing dominance or overdominance in expression, except for one direction of one cross, which showed large mis-expression in the testis. We suggest that, as time passes, more genes come to influence expression, and if there is no directional dominance, additivity becomes increasingly more likely, up to a threshold beyond which there is F(1) hybrid breakdown. Some previous studies on different organisms have found a large degree of dominance, commonly at shorter taxonomic differences. We surveyed these findings and show that the most consistent association exists between the amount of additivity detected in a study and the expression analysis method (in particular microarray platform), suggesting that at least some of the differences among studies might be methodological. Most studies agree with ours in that within-locus additivity seems to be general mode of inheritance for transcript expression. Differentially expressed transcripts identified in our screen among subspecies of house mice are candidate genes that could be involved in reproductive isolation between these subspecies.