Month: September 2022

REPLICATION ERRORS. "The match between events at the cellular and epidemiological level lies in the error-prone replicative machinery that manifests in every environment in which viruses multiply." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

KEY DRIVERS OF SWARMS. "Two key parameters that explain the biological relevance of the rapid formation of mutant swarms during viral replication are the rate at which mutations are introduced during RNA genome copying, and the genome size." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

MASSIVE MUTATION RATE. "Mutation rates have been estimated by independent genetic and biochemical approaches to be in the range of 10(−3) – 10(−5) mutations introduced per nucleotide copied, almost a million-fold higher than standard mutation rates operating on cellular DNA. This difference led Holland et al. to emphasize in a seminal paper a number of disease implications of a rapidly evolving RNA world immersed in a far more static cellular DNA world." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

PERFECT STORM. "Since the size of RNA viral genomes lies between 3 kb and 33 kb, close to the inverse of the mutation rate, it is thought that it is unlikely to produce progeny RNAs identical to the parental genome even within the confined limits of a single replicative unit (each one of the replication complexes) within a single infected cell." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DYNAMIC CONSEQUENCE. "Thus, formation of mutant spectra with an abundance of single point mutants (and gradually decreasing proportions of double, triple and multiple mutants) is a necessary consequence of the mutation rate-genome size relationship." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

NEGATIVE SELECTION. "Mutant swarm generation might be prevented only if negative (or purifying) selection eliminated the great majority of newly arising mutant genomes, which is not the case. Current evidence suggests that a considerable proportion of mutants might be eliminated by negative selection, but it is not clear whether all mutations considered lethal by standard measurements of viral production might not be in reality low fitness variants that can populate low frequency levels of mutant spectra, either because they can replicate minimally or because they are helped by complementation." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

SINGLE ENTITY MUTANT SWARMS. "A realization of recent years is that mutant swarms are not mere collections of mutants ranked by a mutation-selection balance that act independently of each other. Rather, very often the mutant ensemble acts as a unit of selection due to interactions among its members." https://lnkd.in/dJdEQAk View in LinkedIn

GROUP SELECTION. "Two types of interactions have been evidenced: negative interactions (also termed interfering interactions) by which some genomes affect negatively the replication of other genomes of the same ensemble, and positive interactions (akin to classical complementation) by which genomes reinforce each other to achieve a higher replication rate. The result of these interactions is that evolution operates at the level of the population, a process often called ‘group selection”." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

INTERACTIONS. "It is worth noting that these interactions occur among different genomes, so that the effects are different from those of positive or negative epistasis that are established between mutations within the same genome." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

SO ENDS this first of two weekends on mutant RNA viral swarms or quasispecies. These highly proliferative, highly mutating populations of viruses offer possible insights into a RNA-first origin of life scenario. These shape-shifting populations evolve very fast, adapt to new circumstances, and show dramatic phenotypic flexibility. Next weekend we look at some of the clinical implications of these viruses. View in LinkedIn