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07-10-2021, 08:01 PM
New insights into the evolution of human Y chromosome palindromes through mutation and gene conversion (https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddab189/6317807)
Maria Bonito, Eugenia D’Atanasio, Francesco Ravasini, Selene Cariati, Andrea Finocchio, Andrea Novelletto, Beniamino Trombetta, Fulvio Cruciani

About one quarter of the euchromatic portion of the male-specific region of the human Y chromosome consists of large duplicated sequences organized in eight palindromes (termed P1-P8), which undergo arm-to arm gene conversion, a proposed mechanism for maintaining their sequence integrity. Although the relevance of gene conversion in the evolution of palindromic sequences has been profoundly recognized, the dynamic of this mechanism is still nuanced. To shed light into the evolution of these genomic elements, we performed a high-depth (50) targeted next generation sequencing of the palindrome P6 in 157 subjects belonging to the most divergent evolutionary lineages of the Y chromosome. We found 118 new paralogous sequence variants, which were placed into the context of a robust Y chromosome phylogeny based on 7240 SNPs of the X-degenerate region. We mapped along the phylogeny 80 gene conversion events that shaped the diversity of P6 arms during recent human history. In contrast to previous studies, we demonstrated that arm-to-arm gene conversion, which occurs at a rate of 6.01  10−6 conversions/base/year, is not biased towards the retention of the ancestral state of sequences. We also found a significantly lower mutation rate of the arms (6.18  10−10 mutations/base/year) compared to the spacer (9.16  10−10 mutations/base/year), a finding that may explain the observed higher inter-species conservation of arms, without invoking any bias of conversion. Finally, by formally testing the mutation/conversion balance in P6, we found that the arms of this palindrome reached a steady-state equilibrium between mutation and gene conversion.

MSY phylogenetic tree
In order to shed light on the evolutionary dynamics of the P6 palindrome arms, we need to
reconstruct the phylogenetic relationships among the 157 Y chromosomes here sequenced for the
palindromic regions. To this aim, we re-analysed the genetic variation within ~3.3 Mb (supplementary table
1) of the X-degenerate portion of the MSY for exactly the same Y chromosomes (supplementary table 2) that
were previously sequenced at high-depth (about 50 ) (23, 24). Moreover, we included in the analysis 4
precisely radiocarbon-dated ancient specimens (27–29) used as calibration points for an accurate time
estimate of the tree nodes.

The alignment .bam files of palindrome P6 for the
157 Y chromosomes here analysed are deposited in the European Nucleotide Archive
(https://www.ebi.ac.uk/ena/browser/home) under the study accession number PRJEB44535. The alignment
.bam files of the X-degenerate region of the same 157 chromosomes are available through the European
Nucleotide Archive under the accession number PRJEB24071 (from S101 to S210) and PRJEB25861 (from
S300 to S353).