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

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 co...

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Autores principales:	Rahulsimham Vegesna, Marta Tomaszkiewicz, Paul Medvedev, Kateryna D Makova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/d7079b7d3d444c228813a9406c290bc1
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spelling	oai:doaj.org-article:d7079b7d3d444c228813a9406c290bc12021-12-02T20:03:04ZDosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.1553-73901553-740410.1371/journal.pgen.1008369https://doaj.org/article/d7079b7d3d444c228813a9406c290bc12019-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1008369https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404The 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 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.Rahulsimham VegesnaMarta TomaszkiewiczPaul MedvedevKateryna D MakovaPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 15, Iss 9, p e1008369 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Rahulsimham Vegesna Marta Tomaszkiewicz Paul Medvedev Kateryna D Makova Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
description	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 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.
format	article
author	Rahulsimham Vegesna Marta Tomaszkiewicz Paul Medvedev Kateryna D Makova
author_facet	Rahulsimham Vegesna Marta Tomaszkiewicz Paul Medvedev Kateryna D Makova
author_sort	Rahulsimham Vegesna
title	Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
title_short	Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
title_full	Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
title_fullStr	Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
title_full_unstemmed	Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.
title_sort	dosage regulation, and variation in gene expression and copy number of human y chromosome ampliconic genes.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/d7079b7d3d444c228813a9406c290bc1
work_keys_str_mv	AT rahulsimhamvegesna dosageregulationandvariationingeneexpressionandcopynumberofhumanychromosomeampliconicgenes AT martatomaszkiewicz dosageregulationandvariationingeneexpressionandcopynumberofhumanychromosomeampliconicgenes AT paulmedvedev dosageregulationandvariationingeneexpressionandcopynumberofhumanychromosomeampliconicgenes AT katerynadmakova dosageregulationandvariationingeneexpressionandcopynumberofhumanychromosomeampliconicgenes
_version_	1718375690049421312

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

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