Biologists have uncovered virus fragments from the same family of the modern Hepatitis B virus locked inside the genomes of songbirds such as the modern-day zebra finch. This article marks the first time that endogenous hepadnaviruses have been found in any organism. An endogenous virus is one that deposits itself or fragments of itself into the chromosome of an organism, allowing it to be passed from generation-to-generation. Previously, most of these known “fossilized” virus sequences have come from retroviruses. These fragments have been sitting in the bird’s genomes for at least 19 million years, far longer than anyone previously thought this family of viruses had been in existence.
The researchers dated the hepadnavirus fragments by locating them in the same spot on the genome of five species of passerine birds and then tracing those species to a common ancestor that lived more than 19 million years ago. This work provides a glimpse into an ancient viral world that we never knew existed. The results are remarkable – hepadnaviruses, and likely many other viruses as well, are far older than we previously thought. Another surprise is that the older versions of the hepadnaviruses are remarkably similar to today’s viruses. This suggests that the slow evolution of the hepadnaviruses observed in birds indicates that the viruses are, in the long run, better adapted to their hosts than what is suggested by study of the disease-causing Hepatitis B viruses. Genomic fossils like these remarkable hepadnaviral fossils have the prospect of completely revising our preconceived notions about the age and evolution of such viruses.
This study also opens new avenues for research that might help predict and prevent human viral pandemics originating in bird species. Given that they were infected in the past, it is legitimate to think that some of these birds may still carry such viruses today. We can use this discovery as a guide to screen targeted groups of bird species for the presence of new circulating Hepatitis B-like viruses.
Genomic Fossils Calibrate the Long-Term Evolution of Hepadnaviruses. (2010) PLoS Biol 8(9): e1000495. doi:10.1371/journal.pbio.1000495
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.