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.
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.
Vaccinia virus HGT genomesNCBI SRA, PRJNA614958.
- Nels C Elde
- Sarah M Fixsen
- Thomas A Sasani
- Kelsey R Cone
- Nels C Elde
- Nels C Elde
- Stefan Rothenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Karla Kirkegaard, Stanford University School of Medicine, United States
© 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.
As long suspected, poxviruses capture host genes through a reverse-transcription process now shown to be mediated by retrotransposons.
Synthetic autotrophy is a promising avenue to sustainable bioproduction from CO2. Here, we use iterative laboratory evolution to generate several distinct autotrophic strains. Utilising this genetic diversity, we identify that just three mutations are sufficient for Escherichia coli to grow autotrophically, when introduced alongside non-native energy (formate dehydrogenase) and carbon-fixing (RuBisCO, phosphoribulokinase, carbonic anhydrase) modules. The mutated genes are involved in glycolysis (pgi), central-carbon regulation (crp), and RNA transcription (rpoB). The pgi mutation reduces the enzyme’s activity, thereby stabilising the carbon-fixing cycle by capping a major branching flux. For the other two mutations, we observe down-regulation of several metabolic pathways and increased expression of native genes associated with the carbon-fixing module (rpiB) and the energy module (fdoGH), as well as an increased ratio of NADH/NAD+ - the cycle’s electron-donor. This study demonstrates the malleability of metabolism and its capacity to switch trophic modes using only a small number of genetic changes and could facilitate transforming other heterotrophic organisms into autotrophs.