Poxviruses capture host genes by LINE-1 retrotransposition
Abstract
Horizontal gene transfer (HGT) provides a major source of genetic variation. Many viruses, including poxviruses, encode genes with crucial functions directly gained by gene transfer from hosts. The mechanism of transfer to poxvirus genomes is unknown. Using genome analysis and experimental screens of infected cells, we discovered a central role for Long Interspersed Nuclear Element-1 (LINE-1) retrotransposition in HGT to virus genomes. The process recapitulates processed pseudogene generation, but with host messenger RNA directed into virus genomes. Intriguingly, hallmark features of retrotransposition appear to favor virus adaption through rapid duplication of captured host genes on arrival. Our study reveals a previously unrecognized conduit of genetic traffic with fundamental implications for the evolution of many virus classes and their hosts.
Data availability
Sequencing data have been deposited in the NCBI SRA database under project code PRJNA614958.All data generated or analyses during this study are included in the manuscript and supplemental files.
Article and author information
Author details
Funding
National Institutes of Health (R35GM134936)
- Nels C Elde
National Institutes of Health (T32GM007464)
- Sarah M Fixsen
- Thomas A Sasani
National Institutes of Health (T32AI055434)
- Kelsey R Cone
Burroughs Wellcome Fund (1015462)
- Nels C Elde
University of Utah (HA and Edna Benning Presidential Endowed Chair)
- Nels C Elde
National Institutes of Health (R01AI146915)
- Stefan Rothenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Fixsen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Evolutionary Biology
- Microbiology and Infectious Disease
As long suspected, poxviruses capture host genes through a reverse-transcription process now shown to be mediated by retrotransposons.
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- Evolutionary Biology
Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.