E1A Linear Motifs play an adaptive role in mastadenovirus evolution

GLAVINA JULIANA; FAIVOVICH JULIAO; SANCHEZ, IE; RISSO VALERIA; CHEMES L.B.; RODRIGUEZ DE LA VEGA RICARDO; DE PRAT GAY, GONZALO

Posadas, Misiones

Congreso; VIII Argentinian Bioinformatics and Computational Biology Congress; 2017

Asociacion Argentina de Bioinformática y Biología Computacional

Background: Linear Motifs are short sequence elements that mediate protein-protein interactions. Viruses use linear motifs to hijack the host cell machinery inducing pathogenesis in the host. Viruses are under constant selective pressure because of the changing environment and host immune response. Viral linear motifs have been proposed to play a role in adaptive evolution, a claim supported by scarce supporting evidence to date. The adenovirus E1A oncoprotein, unique to the mastadenovirus genus, is densely packed with linear motifs. The wide host diversity and the variability of linear motifs across viral serotypes makes E1A an attractive model to study the role of linear motifs in viral adaptive evolution.Results: We performed a comprehensive reconstruction of the evolutionary history of E1A linear motifs using two methods: Maximum parsimony, considering each motif as a character, and Ancestral sequence reconstruction. Both methods revealed that some motifs showed multiple independent disappearance or appearance events in different branches of the tree, indicating that some instances of the motif did not have common ancestry. Statistical association tests to study co-ocurrence for appearance/disappearance events of linear motifs across mastadenovirus phylogeny showed co-occurrence for both events indicating that the evolution of linear motifs may not be independent. Co-evolutionary analyses superimposing the host and the mastadenoviruses trees showed that host diversity of mastadenoviruses can be explained mainly by duplication events followed by host switch or co-divergence events. Statistical association tests to study co-ocurrence between linear motif appearance/disappearance and mastadenovirus evolutionary events showed the co-occurrence of linear motif dissappearance events with host switch events suggesting that linear motifs may play a role in adaptive evolution.Conclusions: Association tests suggest that appearance and disappearance of linear motifs across mastadenovirus phylogeny is not independent, likely due to functional coupling. Co-evolutionary studies show that co-divergence plays an important evolutionary role in mastadenoviruses diversification, however it is not the only event. Statistical tests suggest that evolutionary events and the appearance and disappearance of the motifs across mastadenovirus phylogeny are not independent suggesting a contribution of linear motifs to adaptive evolution. This study will allow further analyses on the role of linear motifs in adaptive evolution.