Unrestricted migration favours virulent pathogens in experimental metapopulations: evolutionary genetics of a rapacious life history

Understanding pathogen infectivity and virulence requires combining insights from epidemiology, ecology, evolution and genetics. Although theoretical work in these fields has identified population structure as important for pathogen life-history evolution, experimental tests are scarce. Here, we explore the impact of population structure on life-history evolution in phage T4, a viral pathogen of Escherichia coli. The host–pathogen system is propagated as a metapopulation in which migration between subpopulations is either spatially restricted or unrestricted. Restricted migration favours pathogens with low infectivity and low virulence. Unrestricted migration favours pathogens that enter and exit their hosts quickly, although they are less productive owing to rapid extirpation of the host population. The rise of such ‘rapacious’ phage produces a ‘tragedy of the commons’, in which better competitors lower productivity. We have now identified a genetic basis for a rapacious life history. Mutations at a single locus (rI) cause increased virulence and are sufficient to account for a negative relationship between phage competitive ability and productivity. A higher frequency of rI mutants under unrestricted migration signifies the evolution of rapaciousness in this treatment. Conversely, spatially restricted migration favours a more ‘prudent’ pathogen strategy, in which the tragedy of the commons is averted. As our results illustrate, profound epidemiological and ecological consequences of life-history evolution in a pathogen can have a simple genetic cause

Réparation de l'ADN et mutagenèse dans les mitochondries des vertébrés : preuve de l'asymétrie de l'héritage des brins d'ADN

International audienceA variety of endogenous and exogenous factors induce chemical and structural alterations in cellular DNA in addition to the errors occurring throughout DNA synthesis. These types of DNA damage are cytotoxic, miscoding or both and are believed to be at the origin of cancer and other age-related diseases. A human cell, aside from nuclear DNA, contains thousands of copies of mitochondrial DNA (mtDNA), a double-stranded, circular molecule of 16,569 bp. It has been proposed that mtDNA is a critical target of reactive oxygen species: by-products of oxidative phosphorylation that are generated in the organelle during aerobic respiration. Indeed, oxidative damage to mtDNA is more extensive and persistent as compared to that to nuclear DNA. Although transversions are the hallmark of mutations induced by reactive oxygen species, paradoxically, the majority of mtDNA mutations that occur during ageing and cancer are transitions. Furthermore, these mutations show a striking strand orientation bias: T→C/G→A transitions preferentially occur on the light strand, whereas C→T/A→G on the heavy strand of mtDNA. Here, we propose that the majority of mtDNA progenies, created after multiple rounds of DNA replication, are derived from the heavy strand only, owing to asymmetric replication of the DNA strand anchored to the inner membrane via the D-loop structure.Divers facteurs endogènes et exogènes induisent des altérations chimiques et structurelles dans l'ADN cellulaire, en plus des erreurs qui se produisent tout au long de la synthèse de l'ADN. Ces types de dommages à l'ADN sont cytotoxiques, dus à un mauvais codage ou aux deux, et on pense qu'ils sont à l'origine du cancer et d'autres maladies liées à l'âge. Une cellule humaine, outre l'ADN nucléaire, contient des milliers de copies de l'ADN mitochondrial (ADNmt), une molécule circulaire double brin de 16 569 pb. Il a été proposé que l'ADNmt soit une cible critique des espèces réactives de l'oxygène : des sous-produits de la phosphorylation oxydative qui sont générés dans l'organelle pendant la respiration aérobie. En effet, les dommages oxydatifs de l'ADNmt sont plus étendus et plus persistants que ceux de l'ADN nucléaire. Bien que les transversions soient la marque des mutations induites par les espèces réactives de l'oxygène, paradoxalement, la majorité des mutations de l'ADNmt qui se produisent au cours du vieillissement et du cancer sont des transitions. De plus, ces mutations présentent un biais d'orientation des brins frappant : A→G/G→A transitions se produisent de préférence sur le brin léger, tandis que T→C/A→G sur le brin lourd de l'ADNmt. Ici, nous proposons que la majorité des descendants de l'ADNmt, créés après plusieurs cycles de réplication de l'ADN, soient dérivés du brin lourd uniquement, en raison de la réplication asymétrique du brin d'ADN ancré à la membrane interne via la structure en boucle D.Traduit avec www.DeepL.com/Translator (version gratuite