Evolutionary maintenance of filovirus-like genes in bat genomes

Abstract

BackgroundLittle is known of the biological significance and evolutionary maintenance of integrated non-retroviral RNA virus genes in eukaryotic host genomes. Here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. We also estimated the age of filovirus VP35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/Marburgvirus dichotomy for filoviruses.ResultsWe detected homologous copies of VP35-like and NP-like gene integrations in both Old World and New World species of Myotis (bats). We also detected previously unknown VP35-like genes in rodents that are positionally homologous. Comprehensive phylogenetic estimates for filovirus NP-like and VP35-like loci support two main clades with a marsupial and a rodent grouping within the ebolavirus/Lloviu virus/Marburgvirus clade. The concordance of VP35-like, NP-like and mitochondrial gene trees with the expected species tree supports the notion that the copies we examined are orthologs that predate the global spread and radiation of the genus Myotis. Parametric simulations were consistent with selective maintenance for the open reading frame (ORF) of VP35-like genes in Myotis. The ORF of the filovirus-like VP35 gene has been maintained in bat genomes for an estimated 13. 4 MY. ORFs were disrupted for the NP-like genes in Myotis. Likelihood ratio tests revealed that a model that accommodates positive selection is a significantly better fit to the data than a model that does not allow for positive selection for VP35-like sequences. Moreover, site-by-site analysis of selection using two methods indicated at least 25 sites in the VP35-like alignment are under positive selection in Myotis.ConclusionsOur results indicate that filovirus-like elements have significance beyond genomic imprints of prior infection. That is, there appears to be, or have been, functionally maintained copies of such genes in mammals. "Living fossils" of filoviruses appear to be selectively maintained in a diverse mammalian genus (Myotis).

Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences

“…5), which is about the time the Earth emerged from the last ice age. Our estimate is similar to a previous calculation (7,100 to 7,900 years) based on synonymous and nonsynonymous substitution ratios (25) and far younger than other recent assessments using non-clock-based methods that rely on the assumption of filovirus-like elements that appear to have been integrated into the genome of a variety of mammals and subjected to different evolutionary pressures (27,28). Additional approximations of MRCA that resulted in older estimates than those generated in this study differed in terms of more-limited numbers of whole-genome taxa as well as methodology (4,26).…”

“…Although the filoviruses are thought to have originated quite some time ago, age estimates have ranged from a few thousand (25,26) to hundreds of thousands (4) to a few million (27,28) years ago. Further confusing the issue, some authors have presented data indicating that viruses of at least one filovirus species (Zaire ebolavirus) share a most recent common ancestor (MRCA) in the very recent past (29)(30)(31)(32).…”

Ebola from emergence to epidemic: the virus and the disease, global preparedness and perspectives

“…The glycoprotein ORF of EBOV provides two set of gene products, namely 60 to 70 kDa soluble glycoprotein (sGP) and a full-length 150 to 170 kDa glycoprotein (GP) that is located into the viral membrane, through transcriptional editing. In humans, the rates of genetic changes occurring in EBOV may be 100 times slower than that in influenza A viruses; however, the divergence of EBOV was reported to have taken place several thousand years ago [13,14]. The EBOV envelope glycoprotein (eGP) plays multiple functions in viral pathogenesis as it aids in virus attachment and entry to cells, causes cell rounding, down-regulates host surface proteins, enhances virus assembly and budding, and also mediates widespread inflammation, cytotoxicity, and cellular damage, while secretary glycoprotein (sGP) is secreted by the virus infected host cells [15][16][17].…”

Ebola Virus Disease: Biology, Diagnosis, Treatment and Prevention of Epidemics

“…In several species of bats, rodents and marsupials, VP35-, NP-and L-like Ebola genes have been detected. Only in the related species, fossil copies of Ebola genes are often present in syntenous positions; this indicates that interaction between mammals and Ebola has occurred repeatedly (Taylor et al, 2011 and. Ebola genes present in Ebola sensitive species may be in their wild type or mutant state.…”