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Evolutionary Maintenance of Filovirus-Like Genes in Bat Genomes

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Evolutionary Maintenance of Filovirus-Like Genes in Bat Genomes

Derek J Taylor et al. BMC Evol Biol.

Abstract

Background: Little 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.

Results: We 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.

Conclusions: Our 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).

Figures

Figure 1
Figure 1
Map showing the position of the filovirus VP35-like gene and the nearby LINE-1 reverse transcriptase gene in bats of the genus Myotis. The solid arrows represent an open reading frame (ORF), and the hollow arrow represents a disrupted ORF. Numbers below the arrow show the boundaries of the annotation in the contig.
Figure 2
Figure 2
Midpoint rooted maximum likelihood phylogram of filovirus-like nucleoprotein (NP) nucleotide sequences from vespertilionid bats. Three major geographic clades of the genus Myotis are shown by shaded boxes -- the big brown bat (Eptesicus fuscus) sequence has been added for comparison and to show the rooting that divides Old and New World Myotis. Support values (nonparametric bootstrap support/approximate likelihood ratio tests) are given above the branches. GenBank accession numbers or museum voucher numbers are provided in parentheses. See Additional file 8, Table S3 for details of specimen records and acronyms. Red numbers indicate the sum and presumed phylogenetic position of independent observed disruptions to the open reading frame. The scale bar is based on substitutions per site.
Figure 3
Figure 3
Midpoint rooted maximum likelihood phylogram of filovirus-like VP35 nucleotide sequences from vespertilionid bats. Three major geographic regions are shown by the shaded boxes. Support values (nonparametric bootstrap support/approximate likelihood ratio tests) are given above the branches. GenBank accession numbers or museum voucher numbers are provided in parentheses. See Additional file 8, Table S3 for details of specimen records and acronyms. Arrows show unique indels shared by sister taxa that preserve the open reading frame (i.e. all sequences appear to have an open reading frame in the genus Myotis). Note that the 9 bp deletion is not observed in the homologous sequence from the tarsier (supporting its derived position in New World Myotis sp.). The scale bar is based on substitutions per site.
Figure 4
Figure 4
Histogram showing the distribution of expected disruptions in open reading frame in 1000 simulations of nucleotide evolution of filovirus VP35-like sequences in the bat genus Myotis. The simulations start from a center of tree (COT) ancestor with an ORF and use the best-fit model of substitution and the observed maximum likelihood tree with branch lengths as parameters. The observed number of disruptions (zero) is shown by a red bar - a value found in only 0.008 of the simulations. Note that the simulations are conservative because they do not account for selective maintenance involving indel mutations (see Figure 3).
Figure 5
Figure 5
Comparison of the presumptive residues of the interferon-binding region from filoviruses and filovirus VP35-like regions. Bat residues are colored according to a site-by-site Ka /Ks analysis according to the output from Selecton (i.e., dark purple indicates strong purifying selection and dark orange indicates strong positive selection). See Additional file 6,Table S2 for statistical details and values of Ka /Ks for the full alignment.
Figure 6
Figure 6
Cartoon of idealized genome map of a filovirus showing known mammalian NIRVs and their two major clades. Shown are three gene regions of filovirus genomes that are known to have mammalian NIRVs. Red and blue colored boxes indicate phylogenetic clades. The bat cartoon indicates the gene region in Myotis that appears to have an open reading frame maintained.

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