Modular Evolution of Coronavirus Genomes.

ABSTRACT

The viral family Coronaviridae comprises four genera, termed Alpha-, Beta-, Gamma-, and Deltacoronavirus. Recombination events have been described in many coronaviruses infecting humans and other animals. However, formal analysis of the recombination patterns, both in terms of the involved genome regions and the extent of genetic divergence between partners, are scarce. Common methods of recombination detection based on phylogenetic incongruences (e.g., a phylogenetic compatibility matrix) may fail in cases where too many events diminish the phylogenetic signal. Thus, an approach comparing genetic distances in distinct genome regions (pairwise distance deviation matrix) was set up. In alpha, beta, and delta-coronaviruses, a low incidence of recombination between closely related viruses was evident in all genome regions, but it was more extensive between the spike gene and other genome regions. In contrast, avian gammacoronaviruses recombined extensively and exist as a global cloud of genes with poorly corresponding genetic distances in different parts of the genome. Spike, but not other structural proteins, was most commonly exchanged between coronaviruses. Recombination patterns differed between coronavirus genera and corresponded to the modular structure of the spike recombination traces were more pronounced between spike domains (N-terminal and C-terminal parts of S1 and S2) than within domains. The variability of possible recombination events and their uneven distribution over the genome suggest that compatibility of genes, rather than mechanistic or ecological limitations, shapes recombination patterns in coronaviruses.