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Conserved recombination patterns across coronavirus subgenera.

ABSTRACT: 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 break points 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 break points 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 break-point hotspot locations. We find that while the locations of recombination break points 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 break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.

SUBMITTER: de Klerk A

PROVIDER: S-EPMC9261289 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsHybridization is an important evolutionary process that can have a significant impact on natural plant populations. Eucalyptus species are well known for weak reproductive barriers and extensive hybridization within subgenera, but there is little knowledge of whether patterns of hybridization differ among subgenera. Here, we examine eucalypts of Western Australia's Stirling Range to investigate how patterns of hybridization are associated with landscape and taxon age between the two largest Eucalyptus subgenera: Eucalyptus and Symphyomyrtus. In doing so, we tested a hypothesis of OCBIL (old, climatically buffered, infertile landscape) theory that predicts reduced hybridization on older landscapes.MethodsSingle nucleotide polymorphism markers were applied to confirm the hybrid status, parentage and genetic structure of five suspected hybrid combinations for subg. Eucalyptus and three combinations for subg. Symphyomyrtus.Key resultsEvidence of hybridization was found in all combinations, and parental taxa were identified for most combinations. The older parental taxa assessed within subg. Eucalyptus, which are widespread on old landscapes, were identified as well-defined genetic entities and all hybrids were exclusively F1 hybrids. In addition, many combinations showed evidence of clonality, suggesting that the large number of hybrids recorded from some combinations is the result of long-term clonal spread following a few hybridization events rather than frequent hybridization. In contrast, the species in subg. Symphyomyrtus, which typically occur on younger landscapes and are more recently evolved, showed less distinction among parental taxa, and where hybridization was detected, there were high levels of introgression.ConclusionsReduced hybridization in subg. Eucalyptus relative to extensive hybridization in subg. Symphyomyrtus affirmed the hypothesis of reduced hybridization on OCBILs and demonstrate that clade divergence times, landscape age and clonality are important drivers of differing patterns of speciation and hybridization in Eucalyptus.

Project description:The genus Betacoronavirus, consisting of four main subgenera (Embecovirus, Merbecovirus, Nobecovirus, and Sarbecovirus), encompasses all clinically significant coronaviruses (CoVs), including SARS, MERS, and the SARS-CoV-2 virus responsible for current COVID-19 pandemic. Very few molecular characteristics are known that are specific for the genus Betacoronavirus or its different subgenera. In this study, our analyses of the sequences of four essential proteins of CoVs, viz., spike, nucleocapsid, envelope, and RNA-dependent RNA polymerase (RdRp), identified ten novel molecular signatures consisting of conserved signature indels (CSIs) in these proteins which are specific for the genus Betacoronavirus or its subgenera. Of these CSIs, two 14-aa-conserved deletions found within the heptad repeat motifs 1 and 2 of the spike protein are specific for all betacoronaviruses, except for their shared presence in the highly infectious avian coronavirus. Six additional CSIs present in the nucleocapsid protein and one CSI in the RdRp protein are distinctive characteristics of either the Merbecovirus, Nobecovirus, or Sarbecovirus subgenera. In addition, a 4-aa insert is present in the spike protein, which is uniquely shared by all viruses from the subgenera Merbecovirus, Nobecovirus, and Sarbecovirus, but absent in Embecovirus and all other genera of CoVs. This molecular signature provides evidence that viruses from the three subgenera sharing this CSI are more closely related to each other, and they evolved after the divergence of embecoviruses and other CoVs. As all CSIs specific for different groups of CoVs are flanked by conserved regions, their sequences provide novel means for identifying the above groups of CoVs and for developing novel diagnostic tests. Furthermore, our analyses of the structures of the spike and nucleocapsid proteins show that all identified CSIs are localized in the surface-exposed loops of these protein. It is postulated that these surface loops, through their interactions with other cellular proteins/ligands, play important roles in the biology/pathology of these viruses.

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Conserved recombination patterns across coronavirus subgenera.

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