Effects of epistasis and recombination between vaccine-escape and virulence alleles on the dynamics of pathogen adaptation

McLeod, David V.; Gandon, Sylvain

doi:10.1038/s41559-022-01709-y

Cited by 14 publications

(8 citation statements)

References 68 publications

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“…Pathogen virulence can also differ across the landscape, producing additional variation in disease prevalence [15, 16]. Areas can maintain highly virulent strains due to multiple factors, including the introduction of novel strains to new locations or hosts [17, 18], ease or independence of transmission from affected hosts [19, 20], and the development of novel mutations or adaptations that facilitate the escape from host resistance [21]. Although the interaction between host and pathogen identity is rarely examined, theory suggests that presence of highly resistant species could modify the effects of pathogen virulence creating cold spots of transmission across the landscape [22].…”

Section: Introductionmentioning

confidence: 99%

Contribution of host species and pathogen clade to snake fungal disease hotspots in Europe

Blanvillain

Lorch

Joudrier

et al. 2022

Preprint

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Infectious diseases are influenced by interactions between host and pathogens in variable environments and are rarely homogenous across the landscape. Areas with elevated pathogen burden and transmission may indicate a disruption to steady-state disease dynamics. However, isolating processes that result in increases in infection prevalence and intensity remains a challenge. Here we elucidate the contribution of host species, and pathogen clade in disease hotspots. We examined broad-scale patterns of infection of O. ophidiicola, the pathogen that causes snake fungal disease, in 21 species of snakes across 10 countries in Europe. Disease hotspots were evident across several regions in Europe, and our analyses revealed significant differences in infection based on host species and pathogen clade. Over 80% of positive detections were from host species in the Natrix genus, indicating potential higher susceptibility in this group. The presence of O. ophidiicola genotypes that have been associated with more severe disease in North America, also resulted in high rates of infection compared to genotypes only described from Europe. Elevated infection prevalence was best explained by an interaction between host and pathogen identity which was not uniform across all species. More broadly, these findings present important mechanisms underlying disease hotspots across a disease endemic region.

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Section: Introductionmentioning

confidence: 99%

Contribution of host species and pathogen clade to snake fungal disease hotspots in Europe

Blanvillain

Lorch

Joudrier

et al. 2022

Preprint

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“…This result is at first sight surprising, because recombined proteins present several amino acid differences with respect to their parents as opposed to the single amino acid change of point mutants, and thus one may naively expect that that it is more likely that purifying selection eliminates them. Furthermore, it is surprising that the mean stability of recombined proteins is similar to that of their parents, because recombination disrupts epistatic interactions (Otto and Feldman 1997 ; McLeod and Gandon 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Consequences of Genetic Recombination on Protein Folding Stability

et al. 2022

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Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several protein families, finding less detrimental effects than we previously expected. Although recombination can affect multiple protein sites, we found that the fraction of recombined proteins that are eliminated by negative selection because of insufficient stability is not significantly larger than the corresponding fraction of proteins produced by mutation events. Indeed, although recombination disrupts epistatic interactions, the mean stability of recombinant proteins is not lower than that of their parents. On the other hand, the difference of stability between recombined proteins is amplified with respect to the parents, promoting phenotypic diversity. As a result, at least one third of recombined proteins present stability between those of their parents, and a substantial fraction have higher or lower stability than those of both parents. As expected, we found that parents with similar sequences tend to produce recombined proteins with stability close to that of the parents. Finally, the simulation of protein evolution along the ancestral recombination graph with empirical substitution models commonly used in phylogenetics, which ignore constraints on protein folding stability, showed that recombination favors the decrease of folding stability, supporting the convenience of adopting structurally constrained models when possible for inferences of protein evolutionary histories with recombination.

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“…Once an immunity-adapted variant is circulating in the population, the influence on evolutionary adaptation of the rate at which it arises through mutation is negligible compared to the selection acting on the variant (e.g., the dynamics of the Alpha and Delta variants of SARS-CoV-2 were driven by selection, not by the flux of mutations [ 12 , 13 ]). In this case, the speed of pathogen adaptation is mainly driven by selection and different targeted vaccination strategies may provide ways to slow down this adaptation [ 14 – 16 ].…”

Section: Conceptualizing Pathogen Evolutionmentioning

confidence: 99%

Pathogen evolution during vaccination campaigns

et al. 2022

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Following the initiation of the unprecedented global vaccination campaign against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), attention has now turned to the potential impact of this large-scale intervention on the evolution of the virus. In this Essay, we summarize what is currently known about pathogen evolution in the context of immune priming (including vaccination) from research on other pathogen species, with an eye towards the future evolution of SARS-CoV-2.

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Effects of epistasis and recombination between vaccine-escape and virulence alleles on the dynamics of pathogen adaptation

Cited by 14 publications

References 68 publications

Contribution of host species and pathogen clade to snake fungal disease hotspots in Europe

Contribution of host species and pathogen clade to snake fungal disease hotspots in Europe

Consequences of Genetic Recombination on Protein Folding Stability

Pathogen evolution during vaccination campaigns

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