Dataset Information

Whole-genome mutational biases in bacteria.

ABSTRACT: A fundamental biological question is what forces shape the guanine plus cytosine (GC) content of genomes. We studied the specificity and rate of different mutational biases in real time in the bacterium Salmonella typhimurium under conditions of strongly reduced selection and in the absence of the major DNA repair systems involved in repairing common spontaneous mutations caused by oxidized and deaminated DNA bases. The mutational spectrum was determined by whole-genome sequencing of two S. typhimurium mutants that were serially passaged for 5,000 generations. Analysis of 943 identified base pair substitutions showed that 91% were GC-to-TA transversions and 7% were GC-to-AT transitions, commonly associated with 8-oxoG- and deamination-induced damages, respectively. Other types of base pair substitutions constituted the remaining 2% of the mutations. With regard to mutational biases, there was a significant increase in C-to-T transitions on the nontranscribed strand, and for highly expressed genes, C/G-to-T mutations were more common than expected; however, no significant mutational bias with regard to leading and lagging strands of replication or chromosome position were found. These results suggest that, based on the experimentally determined mutational rates and specificities, a bacterial genome lacking the relevant DNA repair systems could, as a consequence of these underlying mutational biases, very rapidly reduce its GC content.

SUBMITTER: Lind PA

PROVIDER: S-EPMC2584707 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-genome mutational biases in bacteria.

Lind Peter A PA Andersson Dan I DI

Proceedings of the National Academy of Sciences of the United States of America 20081110 46

A fundamental biological question is what forces shape the guanine plus cytosine (GC) content of genomes. We studied the specificity and rate of different mutational biases in real time in the bacterium Salmonella typhimurium under conditions of strongly reduced selection and in the absence of the major DNA repair systems involved in repairing common spontaneous mutations caused by oxidized and deaminated DNA bases. The mutational spectrum was determined by whole-genome sequencing of two S. typh ...[more]

PMID: 19001264

Similar Datasets

Project description:BackgroundLess than two percent of the human genome is protein coding, yet that small fraction harbours the majority of known disease causing mutations. Despite rapidly falling whole genome sequencing (WGS) costs, much research and increasingly the clinical use of sequence data is likely to remain focused on the protein coding exome. We set out to quantify and understand how WGS compares with the targeted capture and sequencing of the exome (exome-seq), for the specific purpose of identifying single nucleotide polymorphisms (SNPs) in exome targeted regions.ResultsWe have compared polymorphism detection sensitivity and systematic biases using a set of tissue samples that have been subject to both deep exome and whole genome sequencing. The scoring of detection sensitivity was based on sequence down sampling and reference to a set of gold-standard SNP calls for each sample. Despite evidence of incremental improvements in exome capture technology over time, whole genome sequencing has greater uniformity of sequence read coverage and reduced biases in the detection of non-reference alleles than exome-seq. Exome-seq achieves 95% SNP detection sensitivity at a mean on-target depth of 40 reads, whereas WGS only requires a mean of 14 reads. Known disease causing mutations are not biased towards easy or hard to sequence areas of the genome for either exome-seq or WGS.ConclusionsFrom an economic perspective, WGS is at parity with exome-seq for variant detection in the targeted coding regions. WGS offers benefits in uniformity of read coverage and more balanced allele ratio calls, both of which can in most cases be offset by deeper exome-seq, with the caveat that some exome-seq targets will never achieve sufficient mapped read depth for variant detection due to technical difficulties or probe failures. As WGS is intrinsically richer data that can provide insight into polymorphisms outside coding regions and reveal genomic rearrangements, it is likely to progressively replace exome-seq for many applications.

Dataset Information

Whole-genome mutational biases in bacteria.

Publications

Whole-genome mutational biases in bacteria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets