GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands.

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.

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GC-Content Evolution in Bacterial Genomes: The Biased Gene Conversion Hypothesis Expands

PLoS Genetics ◽

10.1371/journal.pgen.1004941 ◽

2015 ◽

Vol 11 (2) ◽

pp. e1004941 ◽

Cited By ~ 111

Author(s):

Florent Lassalle ◽

Séverine Périan ◽

Thomas Bataillon ◽

Xavier Nesme ◽

Laurent Duret ◽

...

Keyword(s):

Gene Conversion ◽

Gc Content ◽

Bacterial Genomes ◽

Biased Gene Conversion

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Genomic GC content drifts slowly downward in most bacterial genomes

10.1101/2020.07.19.211128 ◽

2020 ◽

Author(s):

Bert Ely

Keyword(s):

Gene Conversion ◽

Gc Content ◽

Bacterial Genomes ◽

Base Pairs ◽

Wide Range ◽

Biased Gene Conversion ◽

Prokaryotic Genomes ◽

Genome Content ◽

Genomic Gc Content ◽

Eukaryotic Genomes

AbstractIn every kingdom of life, GC->AT transitions occur more frequently than any other type of mutation due to the spontaneous deamination of cytidine. In eukaryotic genomes, this slow loss of GC base pairs is counteracted by biased gene conversion which increases genomic GC content as part of the recombination process. However, this type of biased gene conversion has not been observed in bacterial genomes so we hypothesized that GC->AT transitions cause a reduction of genomic GC content in prokaryotic genomes on an evolutionary time scale. To test this hypothesis, we used a phylogenetic approach to analyze triplets of closely related genomes representing a wide range of the bacterial kingdom. The resulting data indicate that genomic GC content is slowly declining in bacterial genomes where GC base pairs comprise 40% or more of the total genome. In contrast, genomes containing less than 40% GC base pairs have fewer opportunities for GC->AT transitions to occur so genomic GC content is relatively stable or actually increasing at a slow rate. It should be noted that this observed change in genomic GC content is the net change in shared parts of the genome and does not apply to parts of the genome that have been lost or acquired since the genomes being compared shared common ancestor. However, a more detailed analysis of two Caulobacter genomes revealed that the acquisition of mobile elements by the two genomes actually reduced the total genome content as well.

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Genomic GC content drifts downward in most bacterial genomes

PLoS ONE ◽

10.1371/journal.pone.0244163 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0244163

Author(s):

Bert Ely

Keyword(s):

Gene Conversion ◽

Gc Content ◽

Bacterial Genomes ◽

Evolutionary Time ◽

Base Pairs ◽

Wide Range ◽

Biased Gene Conversion ◽

Prokaryotic Genomes ◽

Genomic Gc Content ◽

Eukaryotic Genomes

In every kingdom of life, GC->AT transitions occur more frequently than any other type of mutation due to the spontaneous deamination of cytidine. In eukaryotic genomes, this slow loss of GC base pairs is counteracted by biased gene conversion which increases genomic GC content as part of the recombination process. However, this type of biased gene conversion has not been observed in bacterial genomes, so we hypothesized that GC->AT transitions cause a reduction of genomic GC content in prokaryotic genomes on an evolutionary time scale. To test this hypothesis, we used a phylogenetic approach to analyze triplets of closely related genomes representing a wide range of the bacterial kingdom. The resulting data indicate that genomic GC content is drifting downward in bacterial genomes where GC base pairs comprise 40% or more of the total genome. In contrast, genomes containing less than 40% GC base pairs have fewer opportunities for GC->AT transitions to occur so genomic GC content is relatively stable or actually increasing. It should be noted that this observed change in genomic GC content is the net change in shared parts of the genome and does not apply to parts of the genome that have been lost or acquired since the genomes being compared shared common ancestor. However, a more detailed analysis of two Caulobacter genomes revealed that the acquisition of mobile elements by the two genomes actually reduced the total genomic GC content as well.

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Periodic variation of mutation rates in bacterial genomes associated with replication timing

10.1101/195818 ◽

2017 ◽

Author(s):

Marcus M. Dillon ◽

Way Sung ◽

Michael Lynch ◽

Vaughn S. Cooper

Keyword(s):

Vibrio Fischeri ◽

Bacterial Species ◽

Replication Timing ◽

Small Chromosome ◽

Burkholderia Cenocepacia ◽

Mutation Rates ◽

Base Substitution ◽

Large Chromosome ◽

Bacterial Genomes ◽

Substitution Mutation

ABSTRACTThe causes and consequences of spatiotemporal variation in mutation rates remains to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes:Vibrio fischeri, Vibrio cholerae, andBurkholderia cenocepacia. Following five evolution experiments with these bacteria conducted in the near-absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base-substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosome ofV. fischeriandV. cholerae, where concurrently replicated regions experience similar base-substitution mutation rates. The base-substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates as the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base-substitution rates, which along with the inferred ~800 Kb wave period suggests that the source of the periodicity is not sequence-specific but rather a systematic process related to the cell cycle. These results support the notion that base-substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load.

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Evidence for strong fixation bias at 4-fold degenerate sites across genes in the great tit genome

10.1101/436618 ◽

2018 ◽

Cited By ~ 1

Author(s):

Toni I. Gossmann ◽

Mathias Bockwoldt ◽

Lilith Diringer ◽

Friedrich Schwarz ◽

Vic-Fabienne Schumann

Keyword(s):

Gene Conversion ◽

Sequence Data ◽

Bird Species ◽

Gc Content ◽

Great Tit ◽

Genomic Features ◽

Conversion Rates ◽

Biased Gene Conversion ◽

The Impact ◽

Fixation Bias

ABSTRACTIt is well established that GC content varies across the genome in many species and that GC biased gene conversion, one form of meiotic recombination, is likely to contribute to this heterogeneity. Bird genomes provide an extraordinary system to study the impact of GC biased gene conversion owed to their specific genomic features. They are characterised by a high karyotype conservation with substantial heterogeneity in chromosome sizes, with up to a dozen large macrochromosomes and many smaller microchromosomes common across all bird species. This heterogeneity in chromosome morphology is also reflected by other genomic features, such as smaller chromosomes being gene denser, more compact and more GC rich relative to their macrochromosomal counterparts - illustrating that the intensity of GC biased gene conversion varies across the genome. Here we study whether it is possible to infer heterogeneity in GC biased gene conversion rates across the genome using a recently published method that accounts for GC biased gene conversion when estimating branch lengths in a phylogenetic context. To infer the strength of GC biased gene conversion we contrast branch length estimates across the genome both taking and not taking non-stationary GC composition into account. Using simulations we show that this approach works well when GC fixation bias is strong and note that the number of substitutions along a branch is consistently overestimated when GC biased gene conversion is not accounted for. We use this predictable feature to infer the strength of GC dynamics across the great tit genome by applying our new test statistic to data at 4-fold degenerate sites from three bird species - great tit, zebra finch and chicken - three species that are among the best annotated bird genomes to date. We show that using a simple one-dimensional binning we fail to capture a signal of fixation bias as observed in our simulations. However, using a multidimensional binning strategy, we find evidence for heterogeneity in the strength of fixation bias, including AT fixation bias. This highlights the difficulties when combining sequence data across different regions in the genome.

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GC-biased gene conversion in X-Chromosome palindromes conserved in human, chimpanzee, and rhesus macaque

10.1101/2021.04.21.440828 ◽

2021 ◽

Author(s):

Emily K Jackson ◽

Daniel W. Bellott ◽

Helen Skaletsky ◽

David C. Page

Keyword(s):

Rhesus Macaque ◽

Gene Conversion ◽

X Chromosome ◽

Sex Chromosome ◽

Gc Content ◽

Single Copy ◽

Flanking Sequence ◽

X Chromosomes ◽

Wide Range ◽

Biased Gene Conversion

Gene conversion is GC-biased across a wide range of taxa. Large palindromes on mammalian sex chromosomes undergo frequent gene conversion that maintains arm-to-arm sequence identity greater than 99%, which may increase their susceptibility to the effects of GC-biased gene conversion. Here, we demonstrate a striking history of GC-biased gene conversion in 12 palindromes conserved on the X chromosomes of human, chimpanzee, and rhesus macaque. Primate X-chromosome palindrome arms have significantly higher GC content than flanking single-copy sequences. Nucleotide replacements that occurred in human and chimpanzee palindrome arms over the past 7 million years are one-and-a-half times as GC-rich than the ancestral bases they replaced. Using simulations, we show that our observed pattern of nucleotide replacements is consistent with GC-biased gene conversion with a magnitude of 70%, similar to previously reported values based on analyses of human meioses. However, GC-biased gene conversion explains only a fraction of the observed difference in GC content between palindrome arms and flanking sequence, suggesting that additional factors are required to explain elevated GC content in palindrome arms. This work supports a greater than 2:1 preference for GC bases over AT bases during gene conversion, and demonstrates that the evolution and composition of mammalian sex chromosome palindromes is strongly influenced by GC-biased gene conversion.

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Novel metrics for quantifying bacterial genome composition skews

10.1101/176370 ◽

2017 ◽

Author(s):

Lena M. Joesch-Cohen ◽

Max Robinson ◽

Neda Jabbari ◽

Christopher Lausted ◽

Gustavo Glusman

Keyword(s):

Gene Annotation ◽

Bacterial Species ◽

Bacterial Genome ◽

Gc Content ◽

Bacterial Genomes ◽

Genome Composition ◽

Single Genome ◽

A Genome ◽

Dna Strands ◽

Interactive Visualizations

AbstractBackgroundBacterial genomes have characteristic compositional skews, which are differences in nucleotide frequency between the leading and lagging DNA strands across a segment of a genome. It is thought that these strand asymmetries arise as a result of mutational biases and selective constraints, particularly for energy efficiency. Analysis of compositional skews in a diverse set of bacteria provides a comparative context in which mutational and selective environmental constraints can be studied. These analyses typically require finished and well-annotated genomic sequences.ResultsWe present three novel metrics for examining genome composition skews; all three metrics can be computed for unfinished or partially-annotated genomes. The first two metrics, (dot-skew and cross-skew) depend on sequence and gene annotation of a single genome, while the third metric (residual skew) highlights unusual genomes by subtracting a GC content-based model of a library of genome sequences. We applied these metrics to all 7738 available bacterial genomes, including partial drafts, and identified outlier species. A number of these outliers (i.e., Borrelia, Ehrlichia, Kinetoplastibacterium, and Phytoplasma) display similar skew patterns despite only distant phylogenetic relationship. While unrelated, some of the outlier bacterial species share lifestyle characteristics, in particular intracellularity and biosynthetic dependence on their hosts.ConclusionsOur novel metrics appear to reflect the effects of biosynthetic constraints and adaptations to life within one or more hosts on genome composition. We provide results for each analyzed genome, software and interactive visualizations at http://db.systemsbiology.net/gestalt/skew_metrics.

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Background selection and biased gene conversion affect more than 95% of the human genome and bias demographic inferences

eLife ◽

10.7554/elife.36317 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 40

Author(s):

Fanny Pouyet ◽

Simon Aeschbacher ◽

Alexandre Thiéry ◽

Laurent Excoffier

Keyword(s):

Gene Conversion ◽

Purifying Selection ◽

Genomic Diversity ◽

Background Selection ◽

Recombination Rates ◽

Biased Gene Conversion ◽

Synonymous Sites ◽

History Of ◽

Demographic Inference ◽

Genomic Regions

Disentangling the effect on genomic diversity of natural selection from that of demography is notoriously difficult, but necessary to properly reconstruct the history of species. Here, we use high-quality human genomic data to show that purifying selection at linked sites (i.e. background selection, BGS) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. We find that the magnitude and relative importance of BGS and gBGC are largely determined by variation in recombination rate and base composition. Importantly, synonymous sites and non-transcribed regions are also affected, albeit to different degrees. Their use for demographic inference can lead to strong biases. However, by conditioning on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), we identify a set of SNPs that is mostly unaffected by BGS or gBGC, and that avoids these biases in the reconstruction of human history.

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