How and why ampliconic genes survive on the human Y chromosome
Apr 20, 2026·
K Pal, A Greshnova, S Park, BJ Ko, H Pálová, M Steinegger, SLK Pond, S Canzar, KD Makova
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Abstract
The mammalian Y chromosome presents an evolutionary paradox: despite its lack of recombination and propensity for degeneration, it retains multi-copy genes essential for male fertility. To elucidate the reasons and mechanisms for gene survival on the Y in great apes, we integrate telomere-to-telomere assemblies, long-read transcriptomics, protein structure predictions, and selection tests in order to analyze all seven multi-copy gene families on the human Y: BPY2, CDY, DAZ, HSFY, RBMY, TSPY, and VCY. 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 (or domains). Thus, highly ordered proteins are conserved across gene copies and species, even in the presence of copy number and RNA isoform variation. 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.
Type
Publication
bioRxiv
Authors
Postdoctoral Scholar
Karol has a Computer Science background but also enjoys the biological aspect of his work. He did his PhD in Oncology analyzing clonal evolution in leukemias. Currently he is focusing on a more standard type of evolution, that of the primate sex chromosomes. He enjoys creating interactive visual representations of his findings. Outside of the lab Karol likes playing music and scuba diving.
Authors
Postdoctoral Scholar
Currently, Byung June focuses on telomere-to-telomere genome assembly and the functional research of chromatin’s complex structure, particularly in sex chromosomes. Prior to bioinformatics, Byung June majored in conservation genetics, focusing on identifying the genetic diversity and structure of the leopard cat in the South Korea during his M.S. course, supervised by Prof. Soo Hyung Eo. This research sparked his interest in bioinformatics and genome functionality, leading to his false gene gain research collaboration with the Vertebrate Genomes Project during his Ph.D. course at Seoul National University, supervised by Prof. Heebal Kim. Outside of science, Byung June enjoyed playing bass and electric guitar and now enjoys weight lifting and walking in peaceful towns.
Authors
Researcher
Before joining Makova Lab, Hana worked for six years in the field of molecular genetic characterization of pediatric solid tumors and hereditary diseases in Prof. Slaby’s research group at CEITEC, Masaryk University, Brno, Czechia. She got familiar with the interpretation of next generation sequencing data (mainly WES, RNA seq) and a spectrum of molecular genetic methods. She collaborated on several publications and grant projects. In Makova Lab she is responsible for cell cultivation, performing molecular biology methods, and has recently started a new project focusing on the study of telomeres in macaques. Apart from work, she enjoys spending time with her husband and 3 year-old son.
Authors
Professor
Kateryna is interested in genomics, evolution, and human genetics.
Her lab studies mutations using both computational and experimental
approaches. Additional topics of interest include sex chromosome
evolution and genomics of childhood obesity.