Genomic Fossils Calibrate the Long-Term Evolution of Hepadnaviruses

Department of Biology, University of Texas, Arlington, Texas, United States of America.
PLoS Biology (Impact Factor: 9.34). 09/2010; 8(9). DOI: 10.1371/journal.pbio.1000495
Source: PubMed


Because most extant viruses mutate rapidly and lack a true fossil record, their deep evolution and long-term substitution rates remain poorly understood. In addition to retroviruses, which rely on chromosomal integration for their replication, many other viruses replicate in the nucleus of their host's cells and are therefore prone to endogenization, a process that involves integration of viral DNA into the host's germline genome followed by long-term vertical inheritance. Such endogenous viruses are highly valuable as they provide a molecular fossil record of past viral invasions, which may be used to decipher the origins and long-term evolutionary characteristics of modern pathogenic viruses. Hepadnaviruses (Hepadnaviridae) are a family of small, partially double-stranded DNA viruses that include hepatitis B viruses. Here we report the discovery of endogenous hepadnaviruses in the genome of the zebra finch. We used a combination of cross-species analysis of orthologous insertions, molecular dating, and phylogenetic analyses to demonstrate that hepadnaviruses infiltrated repeatedly the germline genome of passerine birds. We provide evidence that some of the avian hepadnavirus integration events are at least 19 My old, which reveals a much deeper ancestry of Hepadnaviridae than could be inferred based on the coalescence times of modern hepadnaviruses. Furthermore, the remarkable sequence similarity between endogenous and extant avian hepadnaviruses (up to 75% identity) suggests that long-term substitution rates for these viruses are on the order of 10(-8) substitutions per site per year, which is a 1,000-fold slower than short-term rates estimated based on the sequences of circulating hepadnaviruses. Together, these results imply a drastic shift in our understanding of the time scale of hepadnavirus evolution, and suggest that the rapid evolutionary dynamics characterizing modern avian hepadnaviruses do not reflect their mode of evolution on a deep time scale.

Download full-text


Available from: Clément Gilbert, Jul 07, 2015
10 Reads
    • "Hepadnaviridae has had a long existence (>200 million years) in 61 different species (Gilbert and Feschotte, 2010; Katzourakis and 62 Gifford, 2010; Suh et al., 2013). The genomic organization of differ- 63 ent HBV lineages has been conserved over a long time, except for 64 gene X which exists only in mammalian HBVs (Locarnini et al., 65 2013). "
    Journal of Hepatology 04/2015; 62:S516. DOI:10.1016/S0168-8278(15)30744-3 · 11.34 Impact Factor
  • Source
    • "Natural virus fossils are difficult to obtain, but the vertical inheritance of EPRV sequences has provided an unexpected opportunity for genetic and evolutionary study of pararetroviruses on a long-term scale. The age of an endogenization event can be estimated by examining the orthologous EPRV insertions at a specific locus among host species with known phylogenetic relationships (Gayral et al., 2010; Gilbert and Feschotte, 2010). In addition, independent viral invasion events in different host populations generated distinct EPRV endogenization patterns (Chessa et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Viral fossils in rice genomes are a best entity to understand ancient pararetrovirus activities through host plant history because of our advanced knowledge of the genomes and evolutionary history with rice and its related species. Here, we explored organization, geographic origins and genealogy of rice pararetroviruses, which were turned into endogenous rice tungro bacilliform virus-like (eRTBVL) sequences. About 300 eRTBVL sequences from three representative rice genomes were clearly classified into six families. Most of the endogenization events of the eRTBVLs were initiated before differentiation of the rice progenitor (> 160,000 years ago). We successfully followed the genealogy of old relic viruses during rice speciation, and inferred the geographical origins for these viruses. Possible virus genomic sequences were explained mostly by recombinations between different virus families. Interestingly, we discovered that only a few recombination events among the numerous occasions had determined the virus genealogy.
    Virology 11/2014; 471-473. DOI:10.1016/j.virol.2014.09.014 · 3.32 Impact Factor
  • Source
    • "Knowledge of divergence times might also affect design of vaccines and programs that identify emerging pathogens. However, the timescale of viral evolution has remained controversial (Gilbert & Feschotte, 2010; Holmes, 2003; Patel, Emerman & Malik, 2011; Sharp & Simmonds, 2011; Wertheim & Kosakovsky Pond, 2011). Fossil and geographic calibrations are normally absent and evolutionary rates based on isolation dates of historical strains often grossly underestimate long-term divergences. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An understanding of the timescale of evolution is critical for comparative virology but remains elusive for many RNA viruses. Age estimates based on mutation rates can severely underestimate divergences for ancient viral genes that are evolving under strong purifying selection. Paleoviral dating, however, can provide minimum age estimates for ancient divergence, but few orthologous paleoviruses are known within clades of extant viruses. For example, ebolaviruses and marburgviruses are well-studied mammalian pathogens, but their comparative biology is difficult to interpret because the existing estimates of divergence are controversial. Here we provide evidence that paleoviral elements of two genes (ebolavirus-like VP35 and NP) in cricetid rodent genomes originated after the divergence of ebolaviruses and cuevaviruses from marburgviruses. We provide evidence of orthology by identifying common paleoviral insertion sites among the rodent genomes. Our findings indicate that ebolaviruses and cuevaviruses have been diverging from marburgviruses since the early Miocene.
    PeerJ 09/2014; 2(1). DOI:10.7717/peerj.556 · 2.11 Impact Factor
Show more