Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated ‘mutational fitness’ of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.

Although fossil evidence suggests the existence of an early muscular system in the ancient cnidarian jellyfish from the early Cambrian Kuanchuanpu biota (ca. 535 Ma), south China, the mechanisms underlying the feeding and respiration of the early jellyfish are conjectural. Recently, the polyp inside the periderm of olivooids was demonstrated to be a calyx-like structure, most likely bearing short tentacles and bundles of coronal muscles at the edge of the calyx, thus presumably contributing to feeding and respiration. Here, we simulate the contraction and expansion of the microscopic periderm-bearing olivooid Quadrapyrgites via the fluid-structure interaction computational fluid dynamics (CFD) method to investigate their feeding and respiratory activities. The simulations show that the rate of water inhalation by the polyp subumbrella is positively correlated with the rate of contraction and expansion of the coronal muscles, consistent with the previous feeding and respiration hypothesis. The dynamic simulations also show that the frequent inhalation/exhalation of water through the periderm polyp expansion/contraction conducted by the muscular system of Quadrapyrgites most likely represents the ancestral feeding and respiration patterns of Cambrian sedentary medusozoans that predated the rhythmic jet-propelled swimming of the modern jellyfish. Most importantly for these Cambrian microscopic sedentary medusozoans, the increase of body size and stronger capacity of muscle contraction may have been indispensable in the stepwise evolution of active feeding and subsequent swimming in a higher flow (or higher Reynolds number) environment.