Disclosing complex mutational dynamics at a Y chromosome palindrome evolving through intra- and inter-chromosomal gene conversion

The human MSY ampliconic region is mainly composed of large duplicated sequences that are organized in eight palindromes (termed P1–P8), which undergo arm-to-arm gene conversion. Although the importance of these elements is widely recognised, their evolutionary dynamics are still nuanced. Here, we focused on P8 palindrome, which shows a complex evolutionary history, being involved in both intra- and inter-chromosomal gene conversion. To disclose its evolutionary complexity, we performed a high-depth (50×) targeted next-generation-sequencing of this element in 157 subjects belonging to the most divergent lineages of the Y chromosome tree. We found a total of 72 polymorphic paralogous sequence variants that have been exploited to identify 41 Y-Y gene conversion events occurred during recent human history. Through our analysis, we were able to categorize P8 arms into three portions whose molecular diversity was modelled by different evolutionary forces. Notably, the outer region of the palindrome is not involved in any gene conversion events and evolves exclusively through the action of mutational pressure. The inner region is affected by Y-Y gene conversion occurring at a rate of 1.52 × 10-5 conversions/base/year, with no bias towards the retention of the ancestral state of the sequences. In this portion, the GC-biased gene conversion identified is counterbalanced by a mutational bias towards AT bases. Finally, the middle region of the arms is involved, in addition to intra-chromosomal gene conversion, in X-to-Y gene conversion (at a rate of 6.013 × 10-8 conversions/base/year) which is strongly active in the evolution of the VCY/VCX gene family.