Dataset Information

Multiple genetic pathways to similar fitness limits during viral adaptation to a new host.

ABSTRACT: The gain in fitness during adaptation depends on the supply of beneficial mutations. Despite a good theoretical understanding of how evolution proceeds for a defined set of mutations, there is little understanding of constraints on net fitness-whether fitness will reach a limit despite ongoing selection and mutation, and if there is a limit, what determines it. Here, the dsDNA bacteriophage SP6, a virus of Salmonella, was adapted to Escherichia coli K-12. From an isolate capable of modest growth on E. coli, four lines were adapted for rapid growth by protocols differing in use of mutagen, propagation method, and duration, but using the same media, temperature, and a continual excess of the novel host. Nucleotide changes underlying those adaptations differed greatly in number and identity, but the four lines achieved similar absolute fitness at the end, an increase of more than 4000-fold phage descendants per hour. Thus, the fitness landscape allows multiple genetic paths to the same approximate fitness limit. The existence and causes of fitness limits have ramifications to genome engineering, vaccine design, and "lethal mutagenesis" treatments to cure viral infections.

SUBMITTER: Nguyen AH

PROVIDER: S-EPMC3377685 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multiple genetic pathways to similar fitness limits during viral adaptation to a new host.

Nguyen Andre H AH Molineux Ian J IJ Springman Rachael R Bull James J JJ

Evolution; international journal of organic evolution 20110920 2

The gain in fitness during adaptation depends on the supply of beneficial mutations. Despite a good theoretical understanding of how evolution proceeds for a defined set of mutations, there is little understanding of constraints on net fitness-whether fitness will reach a limit despite ongoing selection and mutation, and if there is a limit, what determines it. Here, the dsDNA bacteriophage SP6, a virus of Salmonella, was adapted to Escherichia coli K-12. From an isolate capable of modest growth ...[more]

PMID: 22276534

Similar Datasets

Project description:Replication of positive-strand RNA viruses [(+)RNA viruses] takes place in membrane-bound viral replication complexes (VRCs). Formation of VRCs requires virus-mediated manipulation of cellular lipid synthesis. Here, we report significantly enhanced brome mosaic virus (BMV) replication and much improved cell growth in yeast cells lacking PAH1 (pah1Δ), the sole yeast ortholog of human LIPIN genes. PAH1 encodes Pah1p (phosphatidic acid phosphohydrolase), which converts phosphatidate (PA) to diacylglycerol that is subsequently used for the synthesis of the storage lipid triacylglycerol. Inactivation of Pah1p leads to altered lipid composition, including high levels of PA, total phospholipids, ergosterol ester, and free fatty acids, as well as expansion of the nuclear membrane. In pah1Δ cells, BMV replication protein 1a and double-stranded RNA localized to the extended nuclear membrane, there was a significant increase in the number of VRCs formed, and BMV genomic replication increased by 2-fold compared to wild-type cells. In another yeast mutant that lacks both PAH1 and DGK1 (encodes diacylglycerol kinase converting diacylglycerol to PA), which has a normal nuclear membrane but maintains similar lipid compositional changes as in pah1Δ cells, BMV replicated as efficiently as in pah1Δ cells, suggesting that the altered lipid composition was responsible for the enhanced BMV replication. We further showed that increased levels of total phospholipids play an important role because the enhanced BMV replication required active synthesis of phosphatidylcholine, the major membrane phospholipid. Moreover, overexpression of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication. Conversely, overexpression of PAH1 or plant PAH1 orthologs inhibited BMV replication in yeast or Nicotiana benthamiana plants. Competing with its host for limited resources, BMV inhibited host growth, which was markedly alleviated in pah1Δ cells. Our work suggests that Pah1p promotes storage lipid synthesis and thus represses phospholipid synthesis, which in turn restricts both viral replication and cell growth during viral infection.

Dataset Information

Multiple genetic pathways to similar fitness limits during viral adaptation to a new host.

Publications

Multiple genetic pathways to similar fitness limits during viral adaptation to a new host.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets