Dataset Information

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations.

ABSTRACT: Ampliconic genes are multicopy, with the majority found on sex chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilities, we know little about their copy number distribution and their turnover in human populations. Here, we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read depth on modified X and Y chromosome targets containing only one repetition of each ampliconic gene. Our results reveal extensive standing variation in copy number both within and between human populations for several ampliconic genes. For the Y chromosome, we can infer multiple independent amplifications and losses of these gene copies even within closely related Y haplogroups, that diversified < 50,000 years ago. Moreover, X- and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that X- and Y-linked ampliconic genes with extensive CNV are significantly more expressed than genes with no CNV during meiotic sex chromosome inactivation (for both X and Y) and postmeiotic sex chromosome repression (for the Y chromosome only). While we cannot rule out that the XY-linked ampliconic genes are evolving neutrally, this study gives insights into the distribution of copy number within human populations and demonstrates an extremely fast turnover in copy number of these regions.

SUBMITTER: Lucotte EA

PROVIDER: S-EPMC6028258 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Publications

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations.

Lucotte Elise A EA Skov Laurits L Jensen Jacob Malte JM Macià Moisès Coll MC Munch Kasper K Schierup Mikkel H MH

Genetics 20180516 3

Ampliconic genes are multicopy, with the majority found on sex chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilities, we know little about their copy number distribution and their turnover in human populations. Here, we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Projec ...[more]

PMID: 29769284

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Project description:Recent large-scale genomic studies within human populations have identified numerous genomic regions as copy number variant (CNV). As these CNV regions often overlap coding regions of the genome, large lists of potentially copy number polymorphic genes have been produced that are candidates for disease association. Most of the current data regarding normal genic variation, however, has been generated using BAC or SNP microarrays, which lack precision especially with respect to exons. To address this, we assessed 2,790 candidate CNV genes defined from available studies in nine well-characterized HapMap individuals by designing a customized oligonucleotide microarray targeted specifically to exons. Using exon array comparative genomic hybridization (aCGH), we detected 255 (9%) of the candidates as true CNVs including 134 with evidence of variation over the entire gene. Individuals differed in copy number from the control by an average of 100 gene loci. Both partial- and whole-gene CNVs were strongly associated with segmental duplications (55 and 71%, respectively) as well as regions of positive selection. We confirmed 37% of the whole-gene CNVs using the fosmid end sequence pair (ESP) structural variation map for these same individuals. If we modify the end sequence pair mapping strategy to include low-sequence identity ESPs (98-99.5%) and ESPs with an everted orientation, we can capture 82% of the missed genes leading to more complete ascertainment of structural variation within duplicated genes. Our results indicate that segmental duplications are the source of the majority of full-length copy number polymorphic genes, most of the variant genes are organized as tandem duplications, and a significant fraction of these genes will represent paralogs with levels of sequence diversity beyond thresholds of allelic variation. In addition, these data provide a targeted set of CNV genes enriched for regions likely to be associated with human phenotypic differences due to copy number changes and present a source of copy number responsive oligonucleotide probes for future association studies.

Dataset Information

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations.

Publications

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations.

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