Superhelical Duplex Destabilization and the Recombination Position Effect

Sershen, Cheryl L.; Madden, Sally; Benham, Craig J.

doi:10.1371/journal.pone.0020798

“…High GC content is expected to potentially impact the frequencies at which recombination break points occur in various ways such as (1) predisposing genome regions to form stable secondary structures that could cause pausing of RNA-Dependent RNA polymerase (RdRP) ( Stark et al. 2006 ) ( Experimental Evidence Codes| BioGRID 2021 ), (2) increasing the energy needed to break base-pairs during replication, and increasing the amount of time taken for RdRP to traverse these regions ( Petes and Merker 2002 ; Sershen et al. 2011 ) and, if RdRPs disengages during replication, (3) increasing the probability of re-engagement through annealing with the same or a different template molecule ( Lai 1990 ).…”

Section: Resultsmentioning

confidence: 99%

Conserved recombination patterns across coronavirus subgenera

Klerk

¹

,

Swanepoel

²

,

Lourens

³

et al. 2022

View full text Add to dashboard Cite

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination breakpoints at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination breakpoints across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination breakpoint hot-spot locations. We find that while the locations of recombination breakpoints are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination breakpoints most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination breakpoint distributions in coronavirus genomes sampled from nature.

show abstract

“…Its susceptibility to recombine varies according to insertion site, and positively correlates with the G+C content of the flanking sequences. Calculations have shown that changing the base sequence in these flanks alters the predicted propensity to undergo superhelical strand separation at locations internal to the insert ( 84 ). This is a consequence of the long range coupling induced by superhelicity.…”

Section: Superhelical Transitions In Specific Biological Processesmentioning

confidence: 99%

DNA superhelicity

Benham

2023

Nucleic Acids Research

2

0

View full text Add to dashboard Cite

Closing each strand of a DNA duplex upon itself fixes its linking number L. This topological condition couples together the secondary and tertiary structures of the resulting ccDNA topoisomer, a constraint that is not present in otherwise identical nicked or linear DNAs. Fixing L has a range of structural, energetic and functional consequences. Here we consider how L having different integer values (that is, different superhelicities) affects ccDNA molecules. The approaches used are primarily theoretical, and are developed from a historical perspective. In brief, processes that either relax or increase superhelicity, or repartition what is there, may either release or require free energy. The energies involved can be substantial, sufficient to influence many events, directly or indirectly. Here two examples are developed. The changes of unconstrained superhelicity that occur during nucleosome attachment and release are examined. And a simple theoretical model of superhelically driven DNA structural transitions is described that calculates equilibrium distributions for populations of identical topoisomers. This model is used to examine how these distributions change with superhelicity and other factors, and applied to analyze several situations of biological interest.

show abstract

“…calculated proportions of all nucleotide residues that were G or C between 10 or 20 nucleotide sites up and downstream of detected breakpoint locations). High GC content is expected to potentially impact the frequencies at which recombination breakpoints occur in various ways such as (1) predisposing genome regions to form stable secondary structures that could cause pausing of RNA-Dependent RNA polymerase (RdRP) (Stark et al 2006) (Experimental Evidence Codes | BioGRID 2021), ( 2) increasing the energy needed to break base-pairs during replication, and increasing the amount of time taken for RdRP to traverse these regions (Petes and Merker 2002;Sershen et al 2011) and, if RdRPs disengages during replication, (3) increasing the probability of re-engagement through annealing with the same or a different template molecule (Lai 1990).…”

Section: Breakpoints Tend To Fall At Sites With Lower Than Average Gc Contentmentioning

confidence: 99%

Conserved recombination patterns across coronavirus subgenera

Klerk

¹

,

Swanepoel

²

,

Lourens

³

et al. 2021

Preprint

View full text Add to dashboard Cite

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination breakpoints at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination breakpoints across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination breakpoint hot-spot locations. We find that while the locations of recombination breakpoints are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination breakpoints most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination breakpoint distributions in coronavirus genomes sampled from nature.

show abstract

Superhelical Duplex Destabilization and the Recombination Position Effect

Cited by 4 publications

References 33 publications

Conserved recombination patterns across coronavirus subgenera

Conserved recombination patterns across coronavirus subgenera

DNA superhelicity

Conserved recombination patterns across coronavirus subgenera

Contact Info

Product

Resources

About