Sequence of the mouse Y chromosome

Abstract

The mouse Y chromosome has been studied for over 50 years, from the early sex determination and immunological phenotypes attributed to it in the 1950s, to the several mouse Y permatogenic phenotypes and the sex ratio distortion phenotype that are still being studied today. However, even though the draft sequence of the mouse genome was published in 2000, only 750 kb of the 95 Mb mouse Y chromosome was sequenced at that time. To fill that void, we are sequencing the male-specific portion of the mouse Y, and present the analysis of 72 Mb of the mouse Y chromosome here. We found that the X-degenerate portion of the mouse Y chromosome, the portion that descends from the autosomal progenitors of the mammalian X and Y chromosomes, is highly degenerate, even more so than the human Y's X-degenerate sequence. But the ampliconic portion of the mouse Y has expanded to an incredible degree, taking up 95% of the chromosome. Almost all of the ampliconic portion of the mouse Y chromosome is made up of a single 92 Mb segmental duplication that we have named the Huge Repeat array. The Huge Repeat array is a collection of 150-200 515 kb repeat units. The repeat units are internally repetitive, gene-containing, and have a repeat unit to repeat unit similarity ranging from 99% to 99.999%. This array has no homology to the human Y chromosome. The functions of the Huge Repeat are still unclear, but we do know that it is required for proper sperm head morphology and an equal sex ratio in offspring. Due to the high sequence similarity and the high copy number of the Huge Repeat array, we had to invent new sequencing strategies for the sequencing of the mouse Y chromosome. We used a BAC sequencing approach where BACs were selected for sequencing in iterative rounds of sample sequencing. The mouse Y sequencing effort is still in progress.