Unicellular life balances asymmetric allocation and repair of somatic damage representing the origin of r/K selection.

Over the course of multiple divisions, cells accumulate diverse non-genetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated mitigation strategy is required to prevent eventual population collapse. Strategies for somatic damage control can be divided into two categories, asymmetric allocation and repair, which are not, in principle, mutually exclusive. Through mathematical modelling, we identify the optimal strategy, maximizing the total cell number, over a wide range of environmental and physiological conditions. The optimal strategy is primarily determined by extrinsic (damage-independent) mortality and the physiological model for damage accumulation that can be either independent (linear) or increasing (exponential) with respect to the prior accumulated damage. Under the linear regime, the optimal strategy is either exclusively repair or asymmetric allocation whereas under the exponential regime, the optimal strategy is mixed. Repair is preferred when extrinsic mortality is low, whereas at high extrinsic mortality, asymmetric damage allocation becomes the strategy of choice. We hypothesize that optimization over somatic damage repair and asymmetric allocation in early cellular life forms gave rise to the r and K selection strategies.

Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020.

In 2020, SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the global spread of COVID-19 strains remains unclear. Here, we report an analysis of 3206 whole-genome sequences of SARS-CoV-2 samples from 78 regions of Russia covering the period before the spread of variants of concern (between March and November 2020). We describe recurring imports of multiple COVID-19 strains into Russia throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. While the phylogenetically inferred rate of cross-border transmissions was somewhat reduced during the period of the most stringent border closure, it still remained high, with multiple inferred imports that each led to detectable spread within the country. These results indicate that partial border closure has had little effect on trans-border transmission of variants, which helps explain the rapid global spread of newly arising SARS-CoV-2 variants throughout the pandemic.

Pairs of Mutually Compensatory Frameshifting Mutations Contribute to Protein Evolution.

Insertions and deletions of lengths not divisible by 3 in protein-coding sequences cause frameshifts that usually induce premature stop codons and may carry a high fitness cost. However, this cost can be partially offset by a second compensatory indel restoring the reading frame. The role of such pairs of compensatory frameshifting mutations (pCFMs) in evolution has not been studied systematically. Here, we use whole-genome alignments of protein-coding genes of 100 vertebrate species, and of 122 insect species, studying the prevalence of pCFMs in their divergence. We detect a total of 624 candidate pCFM genes; six of them pass stringent quality filtering, including three human genes: RAB36, ARHGAP6, and NCR3LG1. In some instances, amino acid substitutions closely predating or following pCFMs restored the biochemical similarity of the frameshifted segment to the ancestral amino acid sequence, possibly reducing or negating the fitness cost of the pCFM. Typically, however, the biochemical similarity of the frameshifted sequence to the ancestral one was not higher than the similarity of a random sequence of a protein-coding gene to its frameshifted version, indicating that pCFMs can uncover radically novel regions of protein space. In total, pCFMs represent an appreciable and previously overlooked source of novel variation in amino acid sequences.