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

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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Evolution of Nucleotide Composition in the SARS-CoV-2 Lineage: Implications for Vaccine Design

10.20944/preprints202006.0250.v1 ◽

2020 ◽

Author(s):

Sankar Subramanian

Keyword(s):

Base Composition ◽

Scientific Community ◽

Significant Positive Correlation ◽

Gc Content ◽

Nucleotide Composition ◽

Reverse Direction ◽

Novel Coronavirus ◽

Near Future ◽

Systematic Reduction ◽

Gc Contents

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

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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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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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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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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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Large scale variation in the rate of de novo mutation, base composition, divergence and diversity in humans

10.1101/110452 ◽

2017 ◽

Author(s):

Thomas Smith ◽

Peter Arndt ◽

Adam Eyre-Walker

Keyword(s):

Gene Conversion ◽

Mutation Rate ◽

Base Composition ◽

Large Scale ◽

De Novo ◽

Gc Content ◽

De Novo Mutation ◽

Biased Gene Conversion ◽

Different Types ◽

Scale Variation

AbstractIt has long been suspected that the rate of mutation varies across the human genome at a large scale based on the divergence between humans and other species. It is now possible to directly investigate this question using the large number of de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We show that there is variation in the mutation rate at the 100KB, 1MB and 10MB scale that cannot be explained by variation at smaller scales, however the level of this variation is modest at large scales – at the 1MB scale we infer that ~90% of regions have a mutation rate within 50% of the mean. Different types of mutation show similar levels of variation and appear to vary in concert which suggests the pattern of mutation is relatively constant across the genome and hence unlikely to generate variation in GC-content. We confirm this using two different analyses. We find that genomic features explain less than 50% of the explainable variance in the rate of DNM. As expected the rate of divergence between species and the level of diversity within humans are correlated to the rate of DNM. However, the correlations are weaker than if all the variation in divergence was due to variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. We find no evidence that linked selection affects the relationship between divergence and DNM density. In contrast to divergence, we find that most of the variation in diversity can be explained by variation in the mutation rate. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered.Author summaryUsing a dataset of 40,000 de novo mutations we show that there is large-scale variation in the mutation rate at the 100KB and 1MB scale. We show that different types of mutation vary in concert and in a manner that is not expected to generate variation in base composition; hence mutation bias is not responsible for the large-scale variation in base composition that is observed across human chromosomes. As expected large-scale variation in the rate of divergence between species and the variation within species across the genome, are correlated to the rate of mutation, but the correlation between divergence and the mutation rate is not as strong as they could be. We show that biased gene conversion is responsible for weakening the correlation. In contrast we find that most of the variation across the genome in diversity can be explained by variation in the mutation rate. Finally, we show that the correlation between the rate of mutation in humans and the divergence between humans and other species, weakens as the species become more divergent.

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Base composition changes indicate biased gene conversion is a major factor in the evolution of the Fam53A gene

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.449.13 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Andrew David Bergemann ◽

Joy S. Reidenberg ◽

Jeffrey T. Laitman ◽

Lucy Skrabanek ◽

Isabel Genecin

Keyword(s):

Gene Conversion ◽

Base Composition ◽

Biased Gene Conversion ◽

Composition Changes

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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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