Visser, I. | bioRxiv Science

bioRxiv2021

An adaptive compromise - Conflicting evolutionary pressures on arthropod borne Zika virus dinucleotide composition in mammalian hosts and mosquito vectors

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates, and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wildtype. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG-or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wildtype virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that the genome composition of arthropod-borne flaviviruses is crucial to maintain the balance between high-level replication in the vertebrate host and persistent replication in the mosquito vector.

microbiology↗

bioRxiv2020

Uncertainty-driven regulation of learning and exploration in adolescents: A computational account

Healthy adults flexibly adapt their learning strategies to ongoing changes in uncertainty, a key feature of adaptive behaviour. However, the developmental trajectory of this ability is yet unknown, as developmental studies have not incorporated trial-to-trial variation in uncertainty in their analyses or models. To address this issue, we compared adolescents and adults trial-to-trial dynamics of uncertainty, learning rate, and exploration in two tasks that assess learning in noisy but otherwise stable environments. In an estimation task--which provides direct indices of trial-specific learning rate--both age groups reduced their learning rate over time, as self-reported uncertainty decreased. Accordingly, the estimation data in both groups was better explained by a Bayesian model with dynamic learning rate (Kalman filter) than by conventional reinforcement-learning models. Furthermore, adolescents learning rates asymptoted at a higher level, reflecting an over-weighting of the most recent outcome, and the estimated Kalman-filter parameters suggested that this was due to an overestimation of environmental volatility. In a choice task, both age groups became more likely to choose the higher-valued option over time, but this increase in choice accuracy was smaller in the adolescents. In contrast to the estimation task, we found no evidence for a Bayesian expectation-updating process in the choice task, suggesting that estimation and choice tasks engage different learning processes. However, our modeling results of the choice task suggested that both age groups reduced their degree of exploration over time, and that the adolescents explored overall more than the adults. Finally, age-related differences in exploration parameters from fits to the choice data were mediated by participants volatility parameter from fits to the estimation data. Together, these results suggest that adolescents overestimate the rate of environmental change, resulting in elevated learning rates and increased exploration, which may help understand developmental changes in learning and decision-making. Author SummaryTo successfully learn the value of stimuli and actions, people should take into account their current (un)certainty about these values: Learning rates and exploration should be high when ones value estimates are highly uncertain (in the beginning of learning), and decrease over time as evidence accumulates and uncertainty decreases. Recent studies have shown that healthy adults flexibly adapt their learning strategies based on ongoing changes in uncertainty, consistent with normative learning. However, the development of this ability prior to adulthood is yet unknown, as developmental learning studies have not considered trial-to-trial changes in uncertainty. Here, we show that adolescents, as compared to adults, showed a smaller decrease in both learning rate and exploration over time. Computational modeling revealed that both of these effects were due to adolescents overestimating the amount of environmental volatility, which made them more sensitive to recent relative to older evidence. The overestimation of volatility during adolescence may represent the rapidly changing environmental demands during this developmental period, and can help understand the surge in real-life risk taking and exploratory behaviours characteristic of adolescents.

neuroscience↗