PT  - JOURNAL ARTICLE
AU  - Thomas A. Sasani
AU  - Kelsey R. Cone
AU  - Aaron R. Quinlan
AU  - Nels C. Elde
TI  - Long read sequencing reveals Poxvirus evolution through rapid homogenization of gene arrays
AID  - 10.1101/245373
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 245373
4099  - http://biorxiv.org/content/early/2018/01/09/245373.short
4100  - http://biorxiv.org/content/early/2018/01/09/245373.full
AB  - 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.