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.

IntroductionSince sex-based biological and gender factors influence COVID-19 mortality, we wanted to investigate the difference in mortality rates between women and men in sub-Saharan Africa (SSA).MethodWe included 69 580 cases of COVID-19, stratified by sex (men: n=43 071; women: n=26 509) and age (0–39 years: n=41 682; 40–59 years: n=20 757; 60+ years: n=7141), from 20 member nations of the WHO African region until 1 September 2020. We computed the SSA-specific and country-specific case fatality rates (CFRs) and sex-specific CFR differences across various age groups, using a Bayesian approach.ResultsA total of 1656 deaths (2.4% of total cases reported) were reported, with men accounting for 70.5% of total deaths. In SSA, women had a lower CFR than men (mean CFRdiff = −0.9%; 95% credible intervals (CIs) −1.1% to −0.6%). The mean CFR estimates increased with age, with the sex-specific CFR differences being significant among those aged 40 years or more (40–59 age group: mean CFRdiff = −0.7%; 95% CI −1.1% to −0.2%; 60+ years age group: mean CFRdiff = −3.9%; 95% CI −5.3% to −2.4%). At the country level, 7 of the 20 SSA countries reported significantly lower CFRs among women than men overall. Moreover, corresponding to the age-specific datasets, significantly lower CFRs in women than men were observed in the 60+ years age group in seven countries and 40–59 years age group in one country.ConclusionsSex and age are important predictors of COVID-19 mortality globally. Countries should prioritise the collection and use of sex-disaggregated data so as to design public health interventions and ensure that policies promote a gender-sensitive public health response.

Objective: To quantify the initial spread of COVID-19 in the WHO African region, and to investigate the possible drivers responsible for variation in the epidemic among member states. Design: A cross-sectional study. Setting: COVID-19 daily case and death data from the initial case through 29 November 2020. Participants: 46 countries comprising the WHO African region. Main outcome measures: We used five pandemic response indicators for each country: speed at which the pandemic reached the country, speed at which the first 50 cases accumulated, maximum monthly attack rate, cumulative attack rate, and crude case fatality ratio (CFR). We studied the effect of 13 predictor variables on the country-level variation in them using a principal component analysis, followed by regression. Results: Countries with higher tourism activities, GDP per capita, and proportion of older people had higher monthly (p < 0.001) and cumulative attack rates (p < 0.001) and lower CFRs (p = 0.052). Countries having more stringent early COVID-19 response policies experienced greater delay in arrival of the first case (p < 0.001). The speed at which the first 50 cases occurred was slower in countries whose neighbors had higher cumulative attack rates (p = 0.06). Conclusions: While global connectivity and tourism could facilitate the spread of airborne infectious agents, the observed differences in attack rates between African countries might also be due to differences in testing capacities or age distribution. Wealthy countries managed to minimize adverse outcomes. Further, careful and early implementation of strict government policies, such as restricting tourism, could be pivotal to controlling the COVID-19 pandemic. Evidently, good quality data and sufficient testing capacities are essential to unravel the epidemiology of an outbreak. We thus urge decision-makers to reduce these barriers to ensure rapid responses to future threats to public health and economic stability.

Transmission bottlenecks introduce selection pressures on HIV-1 that vary with the mode of transmission. Recent studies on small cohorts have suggested that stronger selection pressures lead to fitter transmitted/founder (T/F) strains. Manifestations of this selection bias at the population level have remained elusive. Here, we analysed early CD4 cell count measurements reported from ∼340,000 infected heterosexual individuals (HET) and men-who-have-sex-with-men (MSM), across geographies, ethnicities and calendar years. The reduction in CD4 counts early in infection is reflective of the virulence of T/F strains. MSM and HET use predominant modes of transmission, namely, anal and penile-vaginal, with among the largest differences in the selection pressures at transmission across modes. Further, in most geographies, the groups show little inter-mixing, allowing for the differential selection bias to be sustained and amplified. We found that the early reduction in CD4 counts was consistently greater in HET than MSM (P<0.05). To account for inherent variations in baseline CD4 counts, we constructed a metric to quantify the extent of progression to AIDS as the ratio of the reduction in measured CD4 counts from baseline and the reduction associated with AIDS. We found that this progression corresponding to the early CD4 measurements was ∼68% for MSM and ∼87% for HET on average (P<10−4; Cohen’s d, ds = 0.36), reflecting the more severe disease caused by T/F strains in HET than MSM at the population level. Interestingly, the set-point viral load was not different between the groups (ds<0.12), suggesting that MSM were more tolerant and not more resistant to their T/F strains than HET. This difference remained when we controlled for confounding factors using multivariable regression. We concluded that the different selection pressures at transmission have resulted in more virulent T/F strains in HET than MSM. These findings have implications for our understanding of HIV-1 pathogenesis, evolution, and epidemiology.