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The azoospermia factor c region (AZFc), located in the long arm of the human Y chromosome, is frequently involved in chromosome rearrangements, mainly due to non-allelic homologous recombination events that occur between the nearly identical sequences (amplicon) that comprises it. These rearrangements may have major phenotypic effects like spermatogenic failure or other pathologies linked to male infertility. Moreover, they may also be relevant in forensic genetics, since some of the Y chromosome short tandem repeats (Y-STRs) commonly used in forensic analysis are located in amplicons or in inter-amplicon sequences of the AZFc. In a previous study, we identified four phylogenetically related samples with a null allele at DYS448 and a tetrallelic pattern at DYF387S1, two Y-STRs located in the AZFc. Through NGS read depth analysis, we found that the unusual Y-STR pattern may be due to a 1.6 Mb deletion arising concurrently or after a 3.5 Mb duplication event. The observed large genomic rearrangement results in copy number reduction for the RBMY gene family as well as duplication of other AZFc genes. Based on the diversity of 16 additional Y-STRs, we estimated that the duplication/deletion event occurred at least twenty generations ago, suggesting that it has not been affected by negative selection.

The male-specific region of the human Y chromosome (MSY) is characterized by the lack of meiotic recombination and it has long been considered an evolutionary independent region of the human genome. In recent years, however, the idea that human MSY did not have an independent evolutionary history begun to emerge with the discovery that inter-chromosomal gene conversion (ICGC) can modulate the genetic diversity of some portions of this genomic region. Despite the study of the dynamics of this molecular mechanism in humans is still in its infancy, some peculiar features and consequences of it can be summarized. The main effect of ICGC is to increase the allelic diversity of MSY by generating a significant excess of clustered single nucleotide polymorphisms (SNPs) (defined as groups of two or more SNPs occurring in close proximity and on the same branch of the Y phylogeny). On the human MSY, 13 inter-chromosomal gene conversion hotspots (GCHs) have been identified so far, involving donor sequences mainly from the X-chromosome and, to a lesser extent, from autosomes. Most of the GCHs are evolutionary conserved and overlap with regions involved in aberrant X–Y crossing-over. This review mainly focuses on the dynamics and the current knowledge concerning the recombinational landscape of the human MSY in the form of ICGC, on how this molecular mechanism may influence the evolution of the MSY, and on how it could affect the information enclosed within a genomic region which, until recently, appeared to be an evolutionary independent unit.