Host–Virus Cophylogenetic Trajectories: Investigating Molecular Relationships between Coronaviruses and Bat Hosts

Abstract

Bats, with their virus tolerance, social behaviors, and mobility, are reservoirs for emerging viruses, including coronaviruses (CoVs) known for genetic flexibility. Studying the cophylogenetic link between bats and CoVs provides vital insights into transmission dynamics and host adaptation. Prior research has yielded valuable insights into phenomena such as host switching, cospeciation, and other dynamics concerning the interaction between CoVs and bats. Nonetheless, a distinct gap exists in the current literature concerning a comparative cophylogenetic analysis focused on elucidating the contributions of sequence fragments to the co-evolution between hosts and viruses. In this study, we analyzed the cophylogenetic patterns of 69 host–virus connections. Among the 69 host–virus links examined, 47 showed significant cophylogeny based on ParaFit and PACo analyses, affirming strong associations. Focusing on two proteins, ORF1ab and spike, we conducted a comparative analysis of host and CoV phylogenies. For ORF1ab, the specific window ranged in multiple sequence alignment (positions 520–680, 770–870, 2930–3070, and 4910–5080) exhibited the lowest Robinson–Foulds (RF) distance (i.e., 84.62%), emphasizing its higher contribution in the cophylogenetic association. Similarly, within the spike region, distinct window ranges (positions 0–140, 60–180, 100–410, 360–550, and 630–730) displayed the lowest RF distance at 88.46%. Our analysis identified six recombination regions within ORF1ab (positions 360–1390, 550–1610, 680–1680, 700–1710, 2060–3090, and 2130–3250), and four within the spike protein (positions 10–510, 50–560, 170–710, and 230–730). The convergence of minimal RF distance regions with combination regions robustly affirms the pivotal role of recombination in viral adaptation to host selection pressures. Furthermore, horizontal gene transfer reveals prominent instances of partial gene transfer events, occurring not only among variants within the same host species but also crossing host species boundaries. This suggests a more intricate pattern of genetic exchange. By employing a multifaceted approach, our comprehensive strategy offers a nuanced understanding of the intricate interactions that govern the co-evolutionary dynamics between bat hosts and CoVs. This deeper insight enhances our comprehension of viral evolution and adaptation mechanisms, shedding light on the broader dynamics that propel viral diversity.