Asymmetric substitution patterns in the two DNA strands of bacteria

Lobry, Jean R.

doi:10.1093/oxfordjournals.molbev.a025626

Cited by 697 publications

(594 citation statements)

References 31 publications

Supporting

Mentioning

561

Contrasting

Unclassified

Order By: Relevance

“…The average G+T content over all transcripts was 52.6%, close to the predicted value. We note that a G+T compositional excess has also been observed in several bacterial genomes 7 , but it seems to arise from replication rather than transcription 7,19 .…”

supporting

confidence: 52%

Transcription-associated mutational asymmetry in mammalian evolution

et al. 2003

View full text Add to dashboard Cite

Although mutation is commonly thought of as a random process, evolutionary studies show that different types of nucleotide substitution occur with widely varying rates that presumably reflect biases intrinsic to mutation and repair mechanisms 1-4 . A strand asymmetry 5,6 , the occurrence of particular substitution types at higher rates than their complementary types, that is associated with DNA replication has been found in bacteria 7 and mitochondria 8 . A strand asymmetry that is associated with transcription and attributable to higher rates of cytosine deamination on the coding strand has been observed in enterobacteria 9-11 . Here, we describe a qualitatively different transcription-associated strand asymmetry in mammals, which may be a byproduct of transcription-coupled repair 12 in germline cells. This mutational asymmetry has acted over long periods of time to produce a compositional asymmetry, an excess of G+T over A+C on the coding strand, in most genes. The mutational and compositional asymmetries can be used to detect the orientations and approximate extents of transcribed regions.We obtained most of the genomic sequence orthologous to a locus of roughly 1.5 Mb on human chromosome 7 containing nine known genes ( Fig. 1) from each of eight other mammals (chimpanzee, baboon, cow, pig, cat, dog, mouse and rat). In initial analyses ( Fig. 2 and Supplementary Fig. 1 online), we tabulated substitutions that have occurred in this locus in the human and chimpanzee lineages since their last common ancestor. There was a significant strand asymmetry in substitution rates, with the transition Α→G occurring at a 28% higher rate than the complementary transition Τ→C (χ 2 1df = 33.54, P < 0.00001).To examine a possible association with transcription, we tabulated separately the substitutions at transcribed and untranscribed positions, scoring the former with respect to the coding strand (that is, the strand complementary to the template strand for transcription). We saw pronounced asymmetries in the transcribed regions for transition substitutions ( Fig. 2): Α→G transitions were 58% more frequent than Τ→C (χ 2 1df = 72.4, P < 0.00001), and G→A transitions were 18% more frequent than C→Τ (χ 2 1df = 10.01, P < 0.002). These asymmetries were also seen when we considered only substitutions in interspersed repeats in the transcribed regions (Fig. 2). Because such sequences are thought to be non-functional, this indicates that the pattern reflects an asymmetry in neutral mutation, rather than selection. Purine transitions were more frequent and pyrimidine transitions less frequent in transcribed regions than in untranscribed regions (Fig. 2), such that the overall transition rate in interspersed repeats was essentially identical for the transcribed and untranscribed portions of the locus (0.00614 versus 0.00613).To test whether this asymmetry was specific to transcribed regions, we did a 'maximal segment' analysis 13 to identify regions with a significant excess or deficit of purine transitions relative to pyrimidine tran...

show abstract

supporting

confidence: 52%

Transcription-associated mutational asymmetry in mammalian evolution

et al. 2003

View full text Add to dashboard Cite

show abstract

“…The origin and end replication in microbial genomes are often associated with transitions in GC skew (G 2 C=G C) values 24 . In R. prowazekii we observe transitions in the GC skew values at around 0 and 500±600 kb (Fig.…”

Section: General Features Of the Genomementioning

confidence: 99%

“…However, the genes¯anking the dnaA gene differ from the conserved motifs found in Escherichia coli and Bacillus subtilis (rnpA±rpmH±dnaA±dnaN±recF±gyrB). In R. prowazekii, the genes rnpA and rpmH are located in the vicinity of dnaA, but in the reverse orientation compared to the consensus motif, and dnaN, recF and gyrB are located elsewhere.The origin and end replication in microbial genomes are often associated with transitions in GC skew (G 2 C=G C) values 24 . In R. prowazekii we observe transitions in the GC skew values at around 0 and 500±600 kb (Fig.…”

mentioning

confidence: 99%

The genome sequence of Rickettsia prowazekii and the origin of mitochondria

Andersson

Zomorodipour

Andersson

et al. 1998

Nature

1,529

1,093

View full text Add to dashboard Cite

We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The functional pro®les of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R. prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in R. prowazekii. In effect, ATP production in Rickettsia is the same as that in mitochondria. Many genes involved in the biosynthesis and regulation of biosynthesis of amino acids and nucleosides in free-living bacteria are absent from R. prowazekii and mitochondria. Such genes seem to have been replaced by homologues in the nuclear (host) genome. The R. prowazekii genome contains the highest proportion of non-coding DNA (24%) detected so far in a microbial genome. Such non-coding sequences may be degraded remnants of`neutralized' genes that await elimination from the genome. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far.The Rickettsia are a-proteobacteria that multiply in eukaryotic cells only. R. prowazekii is the agent of epidemic, louse-borne typhus in humans. Three features of this endocellular parasite deserve our attention. First, R. prowazekii is estimated to have infected 20±30 million humans in the wake of the First World War and killed another few million following the Second World War (ref. 1). Because it is the descendent of free-living organisms 2±4 , its genome provides insight into adaptations to the obligate intracellular lifestyle, with probable practical value. Second, phylogenetic analyses based on sequences of ribosomal RNA and heat-shock proteins indicate that mitochondria may be derived from the aproteobacteria 5,6 . Indeed, the closest extant relatives of the ancestor to mitochondria seem to be the Rickettsia 7±10 . That modern Rickettsia favour an intracellular lifestyle identi®es these bacteria as the sort of organism that might have initiated the endosymbiotic scenario leading to modern mitochondria 11 . Finally, the genome of R. prowazekii is a small one, containing only 1,111,523 base pairs (bp). Its phylogenetic placement and many other characteristics identify it as a descendant of bacteria with substantially larger genomes 2±4 . Thus Rickettsia, like mitochondria, are good examples of highly derived genomes, the products of several types of reductive evolution.The genome sequence of R. prowazekii indicates that these three features may be related. For example, prokaryotic genomes evolving within a cell dominated by a much larger, eukaryote genome and constrained by bottle-necked population dynamics will tend to lose genetic information 12,13 . Predictable sets of expendable genes will tend to disappear from the prokaryotic genome when they are made redundant by the activit...

show abstract

“…Strand bias is known to be a general feature of microbial genomes, influencing the relative composition in nucleotides [48], codons [30,31], and even amino acids [31] of each replicating strand. This has led to the development of several methods for the determination of origins of replication based on the contrast between the leading and lagging strands.…”

Section: Adaptability Versus Genome Stabilitymentioning

confidence: 99%