Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays

Poxvirus adaptation can involve combinations of recombination-driven gene copy number variation and beneficial single nucleotide variants (SNVs) at the same loci. How these distinct mechanisms of genetic diversification might simultaneously facilitate adaptation to host immune defenses is unknown. W...

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Main Authors: Thomas A Sasani, Kelsey R Cone, Aaron R Quinlan, Nels C Elde
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/35453
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author Thomas A Sasani
Kelsey R Cone
Aaron R Quinlan
Nels C Elde
author_facet Thomas A Sasani
Kelsey R Cone
Aaron R Quinlan
Nels C Elde
author_sort Thomas A Sasani
collection DOAJ
description Poxvirus adaptation can involve combinations of recombination-driven gene copy number variation and beneficial single nucleotide variants (SNVs) at the same loci. How these distinct mechanisms of genetic diversification might simultaneously facilitate adaptation to host immune defenses is unknown. We performed experimental evolution with vaccinia virus populations harboring a SNV in a gene actively undergoing copy number amplification. Using long sequencing reads from the Oxford Nanopore Technologies platform, we phased SNVs within large gene copy arrays for the first time. Our analysis uncovered a mechanism of adaptive SNV homogenization reminiscent of gene conversion, which is actively driven by selection. This study reveals a new mechanism for the fluid gain of beneficial mutations in genetic regions undergoing active recombination in viruses and illustrates the value of long read sequencing technologies for investigating complex genome dynamics in diverse biological systems.
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spelling doaj.art-d8455d8b2f684fe0ae59e37a56e538b62022-12-22T03:24:41ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.35453Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arraysThomas A Sasani0https://orcid.org/0000-0003-2317-1374Kelsey R Cone1https://orcid.org/0000-0002-4547-7174Aaron R Quinlan2https://orcid.org/0000-0003-1756-0859Nels C Elde3https://orcid.org/0000-0002-0426-1377Department of Human Genetics, University of Utah, Salt Lake, United StatesDepartment of Human Genetics, University of Utah, Salt Lake, United StatesDepartment of Human Genetics, University of Utah, Salt Lake, United StatesDepartment of Human Genetics, University of Utah, Salt Lake, United StatesPoxvirus adaptation can involve combinations of recombination-driven gene copy number variation and beneficial single nucleotide variants (SNVs) at the same loci. How these distinct mechanisms of genetic diversification might simultaneously facilitate adaptation to host immune defenses is unknown. We performed experimental evolution with vaccinia virus populations harboring a SNV in a gene actively undergoing copy number amplification. Using long sequencing reads from the Oxford Nanopore Technologies platform, we phased SNVs within large gene copy arrays for the first time. Our analysis uncovered a mechanism of adaptive SNV homogenization reminiscent of gene conversion, which is actively driven by selection. This study reveals a new mechanism for the fluid gain of beneficial mutations in genetic regions undergoing active recombination in viruses and illustrates the value of long read sequencing technologies for investigating complex genome dynamics in diverse biological systems.https://elifesciences.org/articles/35453poxvirusexperimental evolutiongene conversionlong read sequencingcopy number variationvaccinia virus
spellingShingle Thomas A Sasani
Kelsey R Cone
Aaron R Quinlan
Nels C Elde
Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
eLife
poxvirus
experimental evolution
gene conversion
long read sequencing
copy number variation
vaccinia virus
title Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
title_full Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
title_fullStr Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
title_full_unstemmed Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
title_short Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
title_sort long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays
topic poxvirus
experimental evolution
gene conversion
long read sequencing
copy number variation
vaccinia virus
url https://elifesciences.org/articles/35453
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AT aaronrquinlan longreadsequencingrevealspoxvirusevolutionthroughrapidhomogenizationofgenearrays
AT nelscelde longreadsequencingrevealspoxvirusevolutionthroughrapidhomogenizationofgenearrays