The amylase gene cluster in house mice (Mus musculus) was subject to repeated introgression including the rescue of a pseudogene

Background Amylase gene clusters have been implicated in adaptive copy number changes in response to the amount of starch in the diet of humans and mammals. However, this interpretation has been questioned for humans and for mammals there is a paucity of information from natural populations. Results Using optical mapping and genome read information, we show here that the amylase cluster in natural house mouse populations is indeed copy-number variable for Amy2b paralogous gene copies (called Amy2a1 - Amy2a5), but a direct connection to starch diet is not evident. However, we find that the amylase cluster was subject to introgression of haplotypes between Mus musculus sub-species. A very recent introgression can be traced in the Western European populations and this leads also to the rescue of an Amy2b pseudogene. Some populations and inbred lines derived from the Western house mouse (Mus musculus domesticus) harbor a copy of the pancreatic amylase (Amy2b) with a stop codon in the first exon, making it non-functional. But populations in France harbor a haplotype introgressed from the Eastern house mouse (M. m. musculus) with an intact reading frame. Detailed analysis of phylogenetic patterns along the amylase cluster suggest an additional history of previous introgressions. Conclusions Our results show that the amylase gene cluster is a hotspot of introgression in the mouse genome, making it an evolutionary active region beyond the previously observed copy number changes.