Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes

Autoři: Rahulsimham Vegesna aff001;  Marta Tomaszkiewicz aff003;  Paul Medvedev aff002;  Kateryna D. Makova aff001
Působiště autorů: Bioinformatics and Genomics Graduate Program, The Huck Institutes for the Life Sciences, Pennsylvania State University, University Park, PA, United States of America aff001;  Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, United States of America aff002;  Department of Biology, Pennsylvania State University, University Park, PA, United States of America aff003;  Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA, United States of America aff004;  Center for Computational Biology and Bioinformatics, Pennsylvania State University, University Park, PA, United States of America aff005;  Center for Medical Genomics, Pennsylvania State University, University Park, PA, United States of America aff006
Vyšlo v časopise: Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008369
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008369


The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that utilizes read sequencing depth information to estimate Y ampliconic gene copy number per family. We applied this tool to whole-genome sequencing data of 149 men with matched testis expression data whose samples are part of the Genotype-Tissue Expression (GTEx) project. We found that the Y ampliconic gene families with low copy number in humans were deleted or pseudogenized in non-human great apes, suggesting relaxation of functional constraints. Among the Y ampliconic gene families, higher copy number leads to higher expression. Within the Y ampliconic gene families, copy number does not influence gene expression, rather a high tolerance for variation in gene expression was observed in testis of presumably healthy men. No differences in gene expression levels were found among major Y haplogroups. Age positively correlated with expression levels of the HSFY and PRY gene families in the African subhaplogroup E1b, but not in the European subhaplogroups R1b and I1. We also found that expression of five out of six Y ampliconic gene families is coordinated with that of their non-Y (i.e. X or autosomal) homologs. Indeed, five ampliconic gene families had consistently lower expression levels when compared to their non-Y homologs suggesting dosage regulation, while the HSFY family had higher expression levels than its X homolog and thus lacked dosage regulation.

Klíčová slova:

Biology and life sciences – Genetics – Gene expression – Gene regulation – Population genetics – Haplogroups – Evolutionary biology – Evolutionary genetics – Population biology – Cell biology – Chromosome biology – Chromosomes – Sex chromosomes – Y chromosomes – Meiosis – Spermatogenesis – Cell processes – Cell cycle and cell division – Physiology – Reproductive physiology – Medicine and health sciences – Research and analysis methods – Database and informatics methods – Bioinformatics – Sequence analysis – Sequence alignment – Social sciences – Sociology – Human families


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