The mammalian Y chromosome presents an evolutionary paradox: despite its lack of recombination and propensity for degeneration, it retains multicopy genes essential for male fertility. To elucidate the reasons and mechanisms for gene survival on the Y in human and great apes, we integrate telomere-to-telomere (T2T) assemblies, long-read transcriptomics, protein structure predictions, and selection tests in order to analyze multicopy gene families on the human Y. First, we show that similar numbers of gene copies are located within palindromes vs. tandem arrays, and that both architectures are equally effective in homogenizing copies via gene conversion. Second, we reconstruct full-length transcripts from PacBio Iso-Seq data from testis across great apes and reveal that transcript diversity arises from both alternative splicing and copy-specific sequence variation. Structural isoform diversity correlates with the number of exons, whereas sequence isoform diversity correlates with the number of gene copies in a family. Third, we find evidence for purifying selection on genes encoding highly ordered proteins. Thus, highly ordered proteins are conserved across gene copies and species, even in the presence of copy number and RNA isoform variation. Finally, using the Human Pangenome Reference Consortium data, we analyze the composition of palindromes across 142 T2T (or nearly T2T) human Y chromosomes and describe gene conversion facilitated by these structures. Together, our results show that palindrome- and array-mediated homogenization and purifying selection aimed at preserving protein structure jointly enable the survival of fertility-related genes on the non-recombining Y chromosome. These results will inform diagnostic approaches to human Y-linked infertility and studies of the conservation of non-human great apes.
Karol has a background in computational sciences and holds a Master’s degree in bioinformatics from the Faculty of Computer Science at Masaryk University in the Czech Republic. He then worked as a bioinformatician in the Center for Molecular Biology and Genetics at the University Hospital Brno, where he defended his PhD in Oncology. His work revolved around genetic profiling of childhood tumors unresponsive to treatment, the discovery of variants in families with inherited susceptibility to haematological malignancies, and clonal evolution in cancer. With growing interest in biology, Karol joined Kateryna Makova’s lab as a postdoc three years ago. There, he has been working on sex chromosomes: their evolution in great apes and population genetics in humans.