Non-coding regions of the Ebola virus genome contain indispensable phylogenetic and evolutionary information

Abstract

We compared the numbers of nucleotide substitutions occurring in the non-coding regions and coding regions of Ebola virus genomes and found that non-coding regions contain indispensable phylogenetic and evolutionary information. The omission of genetic data from non-coding regions can lead to unreliable phylogenies and inaccurate estimates of evolutionary parameters. EBOV, Ebola Materials and methodsFull-length EBOV genomes identified from the 2014 West African outbreak (n=81; 78 from Sierra Leone and three from Guinea) and previously identified EBOV genomes (n=26) were downloaded from GenBank and aligned using ClustalOmega [2] (Table S1 in Supporting Information).The alignment was 18,960 bp in length.To gain insight into whether the nucleotide substitutions in the non-coding regions bear phylogenetic and evolutionary information, we compiled three different datasets, the full-length genome sequences of EBOV, concatenated coding regions, and the glycoprotein (GP) sequences. The GP protein of EBOV is responsible for receptor binding and fusion of the viral and cellular membranes. Recently, it has been reported to be able to mediate the level of certain microRNAs [3], which could be served as potential targets for Ebola drugs. Phylogenic analyses were performed using a Bayesian evolutionary analysis by sampling trees (Beast) approach [4], and 24 different combinations of molecular clock models (n=3) and coalescent models (n=8) were applied (Table S2 in Supporting Information). Fifty million steps were run and the first five million steps were removed as burn-in. Results obtained from different model combinations were compared using Bayes factor estimator of the marginal likelihood [5]. Maximum clade credibility trees were generated using TreeAnnotator v1.8 with a burn-in