Biology subjects

Pinney, J. W.

Publications and source records attributed to Pinney, J. W..

3 recordsLinked to original sources

bioRxiv2019

The structural evolution of host-pathogen protein interactions: an integrative approach

The evolution of protein-protein interactions (PPIs) is directly influenced by the evolutionary histories of the genes and the species encoding the interacting proteins. When it comes to PPIs of host-pathogen systems, the complexity of their evolution is much higher, as two independent, but biologically associated entities, are involved. In this work, an integrative approach combining phylogenetics, tree reconciliations, ancestral sequence reconstructions, and homology modelling is proposed for studying the evolution of host-pathogen PPIs. As a case study, we analysed the evolution of interactions between herpesviral glycoproteins gD/gG and the cell membrane proteins nectins. By modelling the structures of more than 12,000 ancestral states of these virus-host complexes it was found that in early times of their evolution, these proteins were unable to interact, most probably due to electrostatic incompatibilities between their interfaces. After the event of gene duplication that gave rise to a paralog of gD (known as gG), both protein lineages evolved following distinct functional constraints, with most gD reaching high binding affinities towards nectins, while gG lost such ability, most probably due to a process of neofunctionalization. Based on their favourable interaction energies (negative {Delta}G), it is possible to hypothesize that apart from nectins 1 and 2, some alphaherpesviruses might also use nectins 3 and 4 as cell receptors. These findings show that the proposed integrative method is suitable for modelling the evolution of host-pathogen protein interactions, and useful for raising new hypotheses that broaden our understanding about the evolutionary history of PPIs, and their molecular functioning.

bioinformatics↗

bioRxiv2018

The evolution of protein domain repertoires: shedding light on the origins of herpesviruses

Herpesviruses (HVs) have large genomes that can encode thousands of proteins. Apart from amino acid mutations, protein domain acquisitions, duplications and losses are also common modes of evolution. HV domain repertoires differ across species, and only a core set is shared among all viruses, aspect that raises a question: How have HV domain repertoires diverged while keeping some similarities? To answer such question, we used profile HMMs to search for domains in all possible translated ORFs of fully sequenced HV genomes. With at least 274 domains being identified, we built a matrix of domain counts per species, and applied a parsimony method to reconstruct the ancestral states of these domains along the HV phylogeny. It revealed events of domain gain, duplication and loss over more than 400 millions of years, where Alpha-, Beta- and Gammaherpesviruses expanded and condensed their domain repertoires at distinct rates. Most of the acquired domains perform Modulation and Control, Envelope or Auxiliary functions, categories that showed high flexibility (number of domains) and redundancy (number of copies). Conversely, few gains and duplications were observed for domains involved in Capsid assembly and structure, and DNA Replication, recombination and metabolism. Among the 41 primordial domains encoded by herpesvirus ancestors, 28 are still found in all present-day HVs. Because of their distinct evolutionary strategies, herpesvirus domain repertoires are very specific at the subfamily, genus and species levels. Differences in domain composition may not just explain HV host range and tissue tropism, but also provide hints to the origins of herpesviruses.

evolutionary biology↗

bioRxiv2018

Time-calibrated tree reconciliations reveal frequent losses, intrahost speciations, and host switches in the evolution of herpesviruses

Cospeciation has been suggested to be the main force driving the evolution of herpesviruses, with viral species co-diverging with their hosts along more than 400 million years of evolutionary history. Recent studies, however, have been challenging this assumption, showing that other co-phylogenetic events, such as intrahost speciations and host switches play a central role on their evolution. Most of these studies, however, were performed with undated phylogenies, which may underestimate or overestimate the frequency of certain events. In this study we performed co-phylogenetic analyses using time-calibrated trees of herpesviruses and their hosts. This approach allowed us to (i) infer co-phylogenetic events over time, and (ii) integrate crucial information about continental drift and host biogeography to better understand virus-host evolution. We observed that cospeciations were in fact relatively rare events, taking place mostly after the Late Cretaceous (~100 Millions of years ago). Host switches were particularly common among alphaherpesviruses, where at least 10 transfers were detected. Among beta- and gammaherpesviruses, transfers were less frequent, with intrahost speciations followed by losses playing more prominent roles, especially from the Early Jurassic to the Early Cretaceous, when those viral lineages underwent several intrahost speciations. Our study reinforces the understanding that cospeciations are uncommon events in herpesvirus evolution. More than topological incongruences, mismatches in divergence times were the main disagreements between host and viral phylogenies. In most cases, host switches could not explain such disparities, highlighting the important role of losses and intrahost speciations in the evolution of herpesviruses.

evolutionary biology↗