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Functional Segregation of Overlapping Genes in HIV.

ABSTRACT: Overlapping genes pose an evolutionary dilemma as one DNA sequence evolves under the selection pressures of multiple proteins. Here, we perform systematic statistical and mutational analyses of the overlapping HIV-1 genes tat and rev and engineer exhaustive libraries of non-overlapped viruses to perform deep mutational scanning of each gene independently. We find a "segregated" organization in which overlapped sites encode functional residues of one gene or the other, but never both. Furthermore, this organization eliminates unfit genotypes, providing a fitness advantage to the population. Our comprehensive analysis reveals the extraordinary manner in which HIV minimizes the constraint of overlapping genes and repurposes that constraint to its own advantage. Thus, overlaps are not just consequences of evolutionary constraints, but rather can provide population fitness advantages.

SUBMITTER: Fernandes JD

PROVIDER: S-EPMC5287106 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Functional Segregation of Overlapping Genes in HIV.

Fernandes Jason D JD Faust Tyler B TB Strauli Nicolas B NB Smith Cynthia C Crosby David C DC Nakamura Robert L RL Hernandez Ryan D RD Frankel Alan D AD

Cell 20161201 7

Overlapping genes pose an evolutionary dilemma as one DNA sequence evolves under the selection pressures of multiple proteins. Here, we perform systematic statistical and mutational analyses of the overlapping HIV-1 genes tat and rev and engineer exhaustive libraries of non-overlapped viruses to perform deep mutational scanning of each gene independently. We find a "segregated" organization in which overlapped sites encode functional residues of one gene or the other, but never both. Furthermore ...[more]

PMID: 27984726

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