Druelle, V. | bioRxiv Science

bioRxiv2022

Reversions to consensus are positively selected in HIV-1 and bias substitution rate estimates

HIV-1 is a rapidly evolving virus able to evade host immunity through rapid adaptation during chronic infection. The HIV-1 group M has diversified since its zoonosis into several subtypes at a rate of the order of 10-3 changes per site per year. This rate varies between different parts of the genome and its inference is sensitive to the time scale and diversity spanned by the sequence data used. Higher rates are estimated on short time scales and particularly for within-host evolution, while rate estimates spanning decades or the entire HIV-1 pandemic tend to be lower. The underlying causes of this difference are not well understood. We investigate here the role of rapid reversions toward a preferred evolutionary sequence state on multiple time scales. We show that within-host reversion mutations are under positive selection and contribute substantially to sequence turnover, especially at conserved sites. We then use the rates of reversions and non-reversions estimated from longitudinal within-host data to parametrize a phylogenetic sequence evolution model. Sequence simulation of this model on HIV-1 phylogenies reproduces diversity and apparent evolutionary rates of HIV-1 in gag and pol, suggesting that a tendency to rapidly revert to a consensus-like state can explain much of the time dependence of evolutionary rate estimates in HIV-1.

evolutionary biology↗

bioRxiv2021

Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage-host interactions by composing a well-assorted library of 66 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL collection (BActeriophage SElection for your Laboratory). This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside ten well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to eleven defense systems across different layers of bacterial immunity, and matched these results to the phages host range across a panel of pathogenic enterobacterial strains. Our results reveal clear patterns in the distribution of phage phenotypes and genomic features that highlight systematic differences in the potency of different immunity systems and point towards the molecular basis of receptor specificity in several phage groups. Strong trade-offs were detected between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.

microbiology↗