The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10−3–10−4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments.

IntroductionMollusks play a significant role in marine ecosystems and have economic value for aquaculture. Sometimes, unexpected and unexplained mortalities among mollusks have been described. The role of potential pathogens such as viruses remains unknown due to the lack of molluscan cell cultures, which is one of the major drawbacks to determining the viral role in such mortalities. Several oceanographic studies have suggested a high abundance of viruses in the oceans. Virus identification and understanding of viral interaction with organisms in marine ecosystems are in their infancy. Metatranscriptomics could become a useful tool to identify viruses using a shotgun approach and the growing number of viral genomes and sequences deposited in public databases.MethodsIn this work, several bioinformatics approaches were set up to screen Mollusca RNA sequences to find and confirm viral traces in their transcriptomes. This meta-analysis included an extensive search of SRA datasets belonging to mollusks available in the NCBI database, selecting a total of 55 SRA datasets that were further analyzed searching for viral sequences.ResultsTwenty-two bivalves, 19 cephalopods and 16 gastropods from 16 geographical origins and 17 different tissues were considered. The domain search approach was the most productive method to find viral sequences. This virus search showed that Cephalopoda samples (Idiosepius notoides and Amphioctopus fangsiao) exhibited the highest number of virus identifications. Some of the detected viral sequences were similar or identical to others previously identified. However, 33 putative new viruses were identified and analyzed phylogenetically when the RdRp domain was available. Specifically, Cephalopoda samples showed a considerable number of viruses belonging to the Rhabdoviridae family.

Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several protein families, finding less detrimental effects than we previously expected. Although recombination can affect multiple protein sites, we found that the fraction of recombined proteins that are eliminated by negative selection because of insufficient stability is not significantly larger than the corresponding fraction of proteins produced by mutation events. Indeed, although recombination disrupts epistatic interactions, the mean stability of recombinant proteins is not lower than that of their parents. On the other hand, the difference of stability between recombined proteins is amplified with respect to the parents, promoting phenotypic diversity. As a result, at least one third of recombined proteins present stability between those of their parents, and a substantial fraction have higher or lower stability than those of both parents. As expected, we found that parents with similar sequences tend to produce recombined proteins with stability close to that of the parents. Finally, the simulation of protein evolution along the ancestral recombination graph with empirical substitution models commonly used in phylogenetics, which ignore constraints on protein folding stability, showed that recombination favors the decrease of folding stability, supporting the convenience of adopting structurally constrained models when possible for inferences of protein evolutionary histories with recombination.