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

View ORCID ProfileThomas A. Sasani, View ORCID ProfileKelsey R. Cone, View ORCID ProfileAaron R. Quinlan, View ORCID ProfileNels C. Elde
doi: https://doi.org/10.1101/245373
Thomas A. Sasani
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
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Kelsey R. Cone
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
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Aaron R. Quinlan
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
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  • For correspondence: nelde@genetics.utah.edu aquinlan@genetics.utah.edu
Nels C. Elde
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
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  • For correspondence: nelde@genetics.utah.edu aquinlan@genetics.utah.edu
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Abstract

Large DNA viruses rapidly evolve to defeat host defenses. Poxvirus adaptation can involve combinations of recombination-driven gene copy number variation and beneficial single nucleotide variants (SNVs) at the same locus, yet how these distinct mechanisms of genetic diversification might simultaneously facilitate adaptation to immune blocks is unknown. We performed experimental evolution with a vaccinia virus population harboring a SNV in a gene actively undergoing copy number amplification. Comparisons of virus genomes using the Oxford Nanopore Technologies sequencing platform allowed us to phase SNVs within large gene copy arrays for the first time, and uncovered a mechanism of adaptive SNV homogenization reminiscent of gene conversion, which is actively driven by selection. Our work 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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 09, 2018.
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Long read sequencing reveals Poxvirus evolution through rapid homogenization of gene arrays
Thomas A. Sasani, Kelsey R. Cone, Aaron R. Quinlan, Nels C. Elde
bioRxiv 245373; doi: https://doi.org/10.1101/245373
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Long read sequencing reveals Poxvirus evolution through rapid homogenization of gene arrays
Thomas A. Sasani, Kelsey R. Cone, Aaron R. Quinlan, Nels C. Elde
bioRxiv 245373; doi: https://doi.org/10.1101/245373

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