Independent repeated mutations within the alphaviruses Ross River virus and Barmah Forest virus indicates convergent evolution and past positive selection in ancestral populations despite ongoing purifying selection

Alyssa T Pyke; Daniel J Wilson; Alice Michie; John S Mackenzie; Allison Imrie; Jane Cameron; Stephen L Doggett; John Haniotis; Lara J Herrero; Leon Caly; Stacey E Lynch; Peter T Mee; Eugene T Madzokere; Ana L Ramirez; Devina Paramitha; Jody Hobson-Peters; David W Smith; Richard Weir; Mitchell Sullivan; Julian Druce; Lorna Melville; Jennifer Robson; Robert Gibb; Andrew F van den Hurk; Sebastian Duchene

doi:10.1093/ve/veae080

Independent repeated mutations within the alphaviruses Ross River virus and Barmah Forest virus indicates convergent evolution and past positive selection in ancestral populations despite ongoing purifying selection

Virus Evol. 2024 Sep 13;10(1):veae080. doi: 10.1093/ve/veae080. eCollection 2024.

Authors

Alyssa T Pyke¹, Daniel J Wilson^{2

3}, Alice Michie⁴, John S Mackenzie⁵, Allison Imrie⁴, Jane Cameron¹, Stephen L Doggett⁶, John Haniotis⁶, Lara J Herrero⁷, Leon Caly⁸, Stacey E Lynch⁹, Peter T Mee⁹, Eugene T Madzokere⁷, Ana L Ramirez^{10

11

12}, Devina Paramitha¹³, Jody Hobson-Peters¹³, David W Smith^{6

14}, Richard Weir¹⁵, Mitchell Sullivan¹⁶, Julian Druce⁸, Lorna Melville¹⁵, Jennifer Robson¹⁷, Robert Gibb¹⁸, Andrew F van den Hurk¹, Sebastian Duchene^{19

20}

Affiliations

¹ Public Health Virology Laboratory, Public and Environmental Health Reference Laboratories, Department of Health, Queensland Government, P.O. Box 594, Archerfield, Coopers Plains, Queensland, Australia.
² Big Data Institute, Oxford Population Health, University of Oxford, Li Ka Shing Centre for Health Information and Discovery, Old Road Campus, Oxford OX3 7LF, United Kingdom.
³ Department for Continuing Education, University of Oxford, 1 Wellington Square, Oxford OX1 2JA, United Kingdom.
⁴ School of Biomedical Sciences, University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia.
⁵ Faculty of Health Sciences, Curtin University, G.P.O. Box U1987, Bentley, Western Australia 6845, Australia.
⁶ NSW Health Pathology, Westmead Hospital, 166-174 Hawkesbury Road Westmead, Sydney, New South Wales 2145, Australia.
⁷ Gold Coast Campus, Institute for Glycomics, Griffith University, 1 Parklands Drive, Southport, Queensland 4215, Australia.
⁸ Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
⁹ Agriculture Victoria Research, AgriBio, Centre for AgriBioscience, 5 Ring Road, Bundoora, Victoria 3083, Australia.
¹⁰ College of Public Health, Medical and Veterinary Sciences, James Cook University, P.O. Box 6811, Cairns, Queensland 4870, Australia.
¹¹ Australian Institute of Tropical Health and Medicine, James Cook University, P.O. Box 6811, Cairns, Queensland 4870, Australia.
¹² The Jackson Laboratory, 10 Discovery Drive Connecticut, Farmington, CT 06032, United States of America.
¹³ School of Chemistry and Molecular Biosciences, The University of Queensland, Bdg 68 Cooper Road, St. Lucia, Queensland 4072, Australia.
¹⁴ School of Medicine, University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia.
¹⁵ Department of Primary Industries and Fisheries, Berrimah Veterinary Laboratory, P.O. Box 3000, Darwin, Northern Territory 0801, Australia.
¹⁶ Public and Environmental Health Reference Laboratories, Department of Health, Queensland Government, P.O Box 594 Archerfield, Coopers Plains, Queensland 4108, Australia.
¹⁷ Department of Microbiology and Molecular Pathology, Sullivan Nicolaides Pathology, P.O. Box 2014 Fortitude Valley, Brisbane, Queensland 4006, Australia.
¹⁸ Serology, Pathology Queensland Central Laboratory, Royal Brisbane and Women's Hospital, 40 Butterfield Street Herston, Brisbane, Queensland 4029, Australia.
¹⁹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
²⁰ Evolutionary Dynamics of Infectious Diseases, Department of Computational Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France.

Abstract

Ross River virus (RRV) and Barmah Forest virus (BFV) are arthritogenic arthropod-borne viruses (arboviruses) that exhibit generalist host associations and share distributions in Australia and Papua New Guinea (PNG). Using stochastic mapping and discrete-trait phylogenetic analyses, we profiled the independent evolution of RRV and BFV signature mutations. Analysis of 186 RRV and 88 BFV genomes demonstrated their viral evolution trajectories have involved repeated selection of mutations, particularly in the nonstructural protein 1 (nsP1) and envelope 3 (E3) genes suggesting convergent evolution. Convergent mutations in the nsP1 genes of RRV (residues 248 and 441) and BFV (residues 297 and 447) may be involved with catalytic enzyme mechanisms and host membrane interactions during viral RNA replication and capping. Convergent E3 mutations (RRV site 59 and BFV site 57) may be associated with enzymatic furin activity and cleavage of E3 from protein precursors assisting viral maturation and infectivity. Given their requirement to replicate in disparate insect and vertebrate hosts, convergent evolution in RRV and BFV may represent a dynamic link between their requirement to selectively 'fine-tune' intracellular host interactions and viral replicative enzymatic processes. Despite evidence of evolutionary convergence, selection pressure analyses did not reveal any RRV or BFV amino acid sites under strong positive selection and only weak positive selection for nonstructural protein sites. These findings may indicate that their alphavirus ancestors were subject to positive selection events which predisposed ongoing pervasive convergent evolution, and this largely supports continued purifying selection in RRV and BFV populations during their replication in mosquito and vertebrate hosts.

Keywords: Alphavirus; Barmah Forest virus; Ross River virus; Togaviridae; convergent evolution; discrete-trait analysis.