Genomic GC content drifts slowly downward in most bacterial genomes

Mapping Intimacies ◽

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

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab224 ◽

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

Abstract 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 as 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 since the divergence of human and rhesus macaque explains only a fraction of the observed difference in GC content between palindrome arms and flanking sequence, suggesting that palindromes are older than 29 million years and/or had elevated GC content at the time of their formation. 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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GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands.

10.1101/011023 ◽

2014 ◽

Author(s):

Florent Lassalle ◽

Séverine Périan ◽

Thomas Bataillon ◽

Xavier Nesme ◽

Laurent Duret ◽

...

Keyword(s):

Gene Conversion ◽

Bacterial Species ◽

Gc Content ◽

Base Substitution ◽

Human Populations ◽

Bacterial Genomes ◽

Evolutionary Forces ◽

Evolutionary Force ◽

Biased Gene Conversion ◽

Genomic Regions

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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Non-neutral processes drive the nucleotide composition of non-coding sequences in Drosophila

Biology Letters ◽

10.1098/rsbl.2008.0174 ◽

2008 ◽

Vol 4 (4) ◽

pp. 438-441 ◽

Cited By ~ 28

Author(s):

Penelope R Haddrill ◽

Brian Charlesworth

Keyword(s):

Gene Conversion ◽

X Chromosome ◽

Base Composition ◽

Gc Content ◽

Nucleotide Composition ◽

Mutational Bias ◽

Base Pairs ◽

Coding Sequences ◽

Biased Gene Conversion ◽

Gc Contents

The nature of the forces affecting base composition is a key question in genome evolution. There is uncertainty as to whether differences in the GC contents of non-coding sequences reflect differences in mutational bias, or in the intensity of selection or biased gene conversion. We have used a polymorphism dataset for non-coding sequences on the X chromosome of Drosophila simulans to examine this question. The proportion of GC→AT versus AT→GC polymorphic mutations in a locus is correlated with its GC content. This implies the action of forces that favour GC over AT base pairs, which are apparently strongest in GC-rich sequences.

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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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Biased Gene Conversion and GC-Content Evolution in the Coding Sequences of Reptiles and Vertebrates

Genome Biology and Evolution ◽

10.1093/gbe/evu277 ◽

2014 ◽

Vol 7 (1) ◽

pp. 240-250 ◽

Cited By ~ 33

Author(s):

Emeric Figuet ◽

Marion Ballenghien ◽

Jonathan Romiguier ◽

Nicolas Galtier

Keyword(s):

Gene Conversion ◽

Gc Content ◽

Coding Sequences ◽

Biased Gene Conversion

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Comparison of the sequencing bias of currently available library preparation kits for Illumina sequencing of bacterial genomes and metagenomes

DNA Research ◽

10.1093/dnares/dsz017 ◽

2019 ◽

Vol 26 (5) ◽

pp. 391-398 ◽

Cited By ~ 15

Author(s):

Mitsuhiko P Sato ◽

Yoshitoshi Ogura ◽

Keiji Nakamura ◽

Ruriko Nishida ◽

Yasuhiro Gotoh ◽

...

Keyword(s):

Illumina Sequencing ◽

Bacterial Genome ◽

Gc Content ◽

Throughput Capacity ◽

Metagenomic Data ◽

Library Preparation ◽

Bacterial Genomes ◽

Sequencing Bias ◽

Wide Range ◽

Metagenome Sequencing

Abstract In bacterial genome and metagenome sequencing, Illumina sequencers are most frequently used due to their high throughput capacity, and multiple library preparation kits have been developed for Illumina platforms. Here, we systematically analysed and compared the sequencing bias generated by currently available library preparation kits for Illumina sequencing. Our analyses revealed that a strong sequencing bias is introduced in low-GC regions by the Nextera XT kit. The level of bias introduced is dependent on the level of GC content; stronger bias is generated as the GC content decreases. Other analysed kits did not introduce this strong sequencing bias. The GC content-associated sequencing bias introduced by Nextera XT was more remarkable in metagenome sequencing of a mock bacterial community and seriously affected estimation of the relative abundance of low-GC species. The results of our analyses highlight the importance of selecting proper library preparation kits according to the purposes and targets of sequencing, particularly in metagenome sequencing, where a wide range of microbial species with various degrees of GC content is present. Our data also indicate that special attention should be paid to which library preparation kit was used when analysing and interpreting publicly available metagenomic data.

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