Molecular evolution of Zika virus
as it crossed the Pacific to the Americas
Adriano de Bernardi Schneidera , Robert W. Maloneb,c, Jun-Tao Guoa , Jane Homand , Gregorio Linchangcoa , Zachary L. Wittera , Dylan Vinesetta , Lambodhar Damodarana and Daniel A. Janiesa,*
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, 28223-0001, NC, USA; b Atheric Pharmaceutical, 2981 Zion Road, Troy, VA, 22974 USA; c Class of 2016, Harvard Medical School Global Clinical Scholars Research Training Program, Boston, MA, USA; d ioGenetics LLC, 3591 Anderson Street, Suite 218 Madison, WI 53704, USA Accepted 20 September 2016
Abstract Zika virus was previously considered to cause only a benign infection in humans. Studies of recent outbreaks of Zika virus in the Pacific, South America, Mexico and the Caribbean have associated the virus with severe neuropathology. Viral evolution may be one factor contributing to an apparent change in Zika disease as it spread from Southeast Asia across the Pacific to the Americas. To address this possibility, we have employed computational tools to compare the phylogeny, geography, immunology and RNA structure of Zika virus isolates from Africa, Asia, the Pacific and the Americas. In doing so, we compare and contrast methods and results for tree search and rooting of Zika virus phylogenies. In some phylogenetic analyses we find support for the hypothesis that there is a deep common ancestor between African and Asian clades (the “Asia/Africa” hypothesis). In other phylogenetic analyses, we find that Asian lineages are descendent from African lineages (the “out of Africa” hypothesis). In addition, we identify and evaluate key mutations in viral envelope protein coding and untranslated terminal RNA regions. We find stepwise mutations that have altered both immunological motif sets and regulatory sequence elements. Both of these sets of changes distinguish viruses found in Africa from those in the emergent Asia–Pacific–Americas lineage. These findings support the working hypothesis that mutations acquired by Zika virus in the Pacific and Americas contribute to changes in pathology. These results can inform experiments required to elucidate the role of viral genetic evolution in changes in neuropathology, including microcephaly and other neurological and skeletomuscular issues in infants, and Guillain-Barre syndrome in adults.
Cladistics Cladistics (2016) 1–20 10.1111/cla.12178