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Ananthu James

Publications and source records attributed to Ananthu James.

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Challenges of Equitable Vaccine Distribution in the COVID-19 Pandemic

The COVID-19 pandemic has led to a need for widespread and rapid vaccine development. As several vaccines have recently been approved for human use or are in different stages of development, governments across the world are preparing comprehensive guidelines for vaccine distribution and monitoring. In this early article, we identify challenges in logistics, health outcomes, user-centric matters, and communication associated with disease-related, individual, societal, economic, and privacy consequences. Primary challenges include difficulty in equitable distribution, vaccine efficacy, duration of immunity, multi-dose adherence, and privacy-focused record-keeping to be HIPAA compliant. While many of these challenges have been previously identified and addressed, some have not been acknowledged from a comprehensive view accounting for unprecedented interactions between challenges and specific populations. The logistics of equitable widespread vaccine distribution in disparate populations and countries of various economic, racial, and cultural constitutions must be thoroughly examined and accounted for. We also describe unique challenges regarding the efficacy of vaccines in specialized populations including children, the elderly, and immunocompromised individuals. Furthermore, we report the potential for understudied drug-vaccine interactions as well as the possibility that certain vaccine platforms may increase susceptibility to HIV. Given these complicated issues, the importance of privacy-focused, user-centric systems for vaccine education and incentivization along with clear communication from governments, organizations, and academic institutions is imperative. These challenges are by no means insurmountable, but require careful attention to avoid consequences spanning a range of disease-related, individual, societal, economic, and security domains.

econ.GN

Fixation probability of a nonmutator in a large population of asexual mutators

In an adapted population of mutators in which most mutations are deleterious, a nonmutator that lowers the mutation rate is under indirect selection and can sweep to fixation. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large population of asexual mutators. We show that when beneficial mutations are absent, the fixation probability is a nonmonotonic function of the mutation rate of the mutator: it first increases sublinearly and then decreases exponentially. We also find that beneficial mutations can enhance the fixation probability of a nonmutator. Our analysis is relevant to an understanding of recent experiments in which a reduction in the mutation rates has been observed.

q-bio.PE

Role of epistasis on the fixation probability of a non-mutator in an adapted asexual population

The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype branching process, the fixation probability of a single non-mutator emerging in a large asexual mutator population is analytically calculated here. The mutator population undergoes deleterious mutations at constant, but at a much higher rate than that of the non-mutator. We find that antagonistic epistasis lowers the chances of mutation rate reduction, while synergistic epistasis enhances it. Below a critical value of epistasis, the fixation probability behaves non-monotonically with variation in mutation rate of the background population. Moreover, the variation of this critical value of the epistasis parameter with the strength of the mutator is discussed in the Appendix. For synergistic epistasis, when selection is varied, the fixation probability reduces overall, with damped oscillations.

q-bio.PE

Fixation probability of rare nonmutator and evolution of mutation rates

Although mutations drive the evolutionary process, the rates at which the mutations occur are themselves subject to evolutionary forces. Our purpose here is to understand the role of selection and random genetic drift in the evolution of mutation rates, and we address this question in asexual populations at mutation-selection equilibrium neglecting selective sweeps. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large asexual population of mutators, and find that a nonmutator is more likely to fix when the deleterious mutation rate of the mutator population is high. Compensatory mutations in the mutator population are found to decrease the fixation probability of a nonmutator when the selection coefficient is large. But, surprisingly, the fixation probability changes nonmonotonically with increasing compensatory mutation rate when the selection is mild. Using these results for the fixation probability and a drift-barrier argument, we find a novel relationship between the mutation rates and the population size. We also discuss the time to fix the nonmutator in an adapted population of asexual mutators, and compare our results with experiments.

q-bio.PE