Linking high GC content to the repair of double strand breaks in prokaryotic genomes

Weissman, Jake L.; Fagan, William F.; Johnson, Philip L. F.

doi:10.1371/journal.pgen.1008493

Cited by 53 publications

(58 citation statements)

References 66 publications

(124 reference statements)

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“…Given its central role in DNA repair, we asked whether any other genome characteristics could also be associated with the presence or absence of NHEJ. First, we verified that the findings of Weissman et al held true for NHEJ+ states as defined in our study (Figure 5A, Supplementary S4-S5, S7C) (Weissman, Fagan, and Johnson 2019). Along with this, we tested two additional characteristics: genome size and growth rate (as measured by the copy number of rRNA operons), both of which could determine the availability or the lack of a homologous template for high fidelity recombination-based repair.…”

Section: Nhej Occurrence Is Associated With Genome Size Growth Rate supporting

confidence: 87%

“…Our study highlights the evolutionary trajectory of NHEJ and central characteristics that may have determined it's sporadic distribution. DSB repair, including NHEJ, has been implicated in shaping bacterial genomes through mutagenesis (Paris et al 2015), HGT (Popa et al 2011) and their effect on genomic GC content (Weissman, Fagan, and Johnson 2019). Given this relationship between repair and genome evolution, it is important to ask how one factor may have influenced the other during bacterial evolution.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Ku-encoding organisms were shown to have higher genomic G+C content (Weissman, Fagan, and Johnson 2019). Given its central role in DNA repair, we asked whether any other genome characteristics could also be associated with the presence or absence of NHEJ.…”

Section: Nhej Occurrence Is Associated With Genome Size Growth Rate mentioning

confidence: 99%

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Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair

Sharda

Badrinarayanan

Seshasayee

2019

Preprint

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DNA double-strand breaks (DSBs) are a threat to genome stability. In all domains of life, DSBs are faithfully fixed via homologous recombination. However, recombination requires the presence of an uncut copy of duplex DNA that can be used as a template for repair. Alternate to this, in the absence of a template, eukaryotes and some prokaryotes also utilize Non-homologous end joining (NHEJ) repair.This pathway, or variations of it, can be error-prone. However, it avoids the lethality of a DSB, making NHEJ an important form of repair. Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. It is unclear as to why many prokaryotic systems lack this pathway. To understand what could have led to the current distribution of NHEJ in bacteria, we carried out comparative genomics and phylogenetic analysis across ~6000 sequenced genomes. Our results show that this repair trait is sporadically distributed across the phylogeny, with a few clades that are completely devoid of it.Ancestral reconstruction suggests that NHEJ was absent in the eubacterial ancestor, followed by primary independent gains as well as secondary losses and gains, in different clades across the bacterial history. Further, our analysis suggests that this pattern of occurrence is consistent with the correlated evolution of NHEJ with key genome characteristics of genome size and growth rates; NHEJ presence in bacteria is associated with large genome sizes and / or slow growth rates, with the former being the dominant correlate. Given the central role these traits may play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by the requirement for efficient DSB repair.

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Section: Nhej Occurrence Is Associated With Genome Size Growth Rate supporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair

Sharda

Badrinarayanan

Seshasayee

2019

Preprint

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“…Recently, Ku-encoding organisms were shown to have higher genomic G + C content ( Weissman et al. 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…7 A and supplementary figs. S4, S5, and S7 C , Supplementary Material online) ( Weissman et al. 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary and Comparative Analysis of Bacterial Nonhomologous End Joining Repair

Sharda

Badrinarayanan

Seshasayee

2020

Genome Biology and Evolution

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DNA double-strand breaks (DSBs) are a threat to genome stability. In all domains of life, DSBs are faithfully fixed via homologous recombination. Recombination requires the presence of an uncut copy of duplex DNA which is used as a template for repair. Alternatively, in the absence of a template, cells utilize error-prone Non-homologous end joining (NHEJ). Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. It is unclear as to why many prokaryotes lack this pathway. Towards understanding what could have led to the current distribution of bacterial NHEJ, we carried out comparative genomics and phylogenetic analysis across ∼6000 genomes. Our results show that this pathway is sporadically distributed across the phylogeny. Ancestral reconstruction further suggests that NHEJ was absent in the eubacterial ancestor, and can be acquired via specific routes. Integrating NHEJ occurrence data for archaea, we also find evidence for extensive horizontal exchange of NHEJ genes between the two kingdoms as well as across bacterial clades. The pattern of occurrence in bacteria is consistent with correlated evolution of NHEJ with key genome characteristics of genome size and growth rate; NHEJ presence is associated with large genome sizes and/or slow growth rates, with the former being the dominant correlate. Given the central role these traits play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by requirement for efficient DSB repair.

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In‐depth analysis of amino acid and nucleotide sequences of Hsp60: How conserved is this protein?

et al. 2022

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Chaperonin Hsp60, as a protein found in all organisms, is of great interest in medicine, since it is present in many tissues and can be used both as a drug and as an object of targeted therapy. Hence, Hsp60 deserves a fundamental comparative analysis to assess its evolutionary characteristics. It was found that the percent identity of Hsp60 amino acid sequences both within and between phyla was not high enough to identify Hsp60s as highly conserved proteins. However, their ATP binding sites are largely conserved. The amino acid composition of Hsp60s remained relatively constant. At the same time, the analysis of the nucleotide sequences showed that GC content in the Hsp60 genes was comparable to or greater than the genomic values, which may indicate a high resistance to mutations due to tight control of the nucleotide composition by DNA repair systems. Natural selection plays a dominant role in the evolution of Hsp60 genes. The degree of mutational pressure affecting the Hsp60 genes is quite low, and its direction does not depend on taxonomy. Interestingly, for the Hsp60 genes from Chordata, Arthropoda, and Proteobacteria the exact direction of mutational pressure could not be determined. However, upon further division into classes, it was found that the direction of the mutational pressure for Hsp60 genes from Fish differs from that for other chordates. The direction of the mutational pressure affects the synonymous codon usage bias. The number of high and low represented codons increases with increasing GC content, which can improve codon usage. Special server has been created for bioinformatics analysis of Hsp60: http://oka.protres.ru:4202/.

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Linking high GC content to the repair of double strand breaks in prokaryotic genomes

Cited by 53 publications

References 66 publications

Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair

Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair

Evolutionary and Comparative Analysis of Bacterial Nonhomologous End Joining Repair

In‐depth analysis of amino acid and nucleotide sequences of Hsp60: How conserved is this protein?

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