Eight percent of your genome derives from retroviruses that inserted themselves into human sex cells millions of years ago. Right now the koala retrovirus (KoRV) is invading koala genomes, a process that can help us understand our own viral lineage and make decisions about managing this vulnerable species.
In a recent study, published in Molecular Biology and Evolution, scientists from the University of Illinois discovered that 39 different KoRVs in a koala’s genome were all endogenous, which means passed down to the koala from one parent or the other; one of the KoRVs was found in both parents.
Koalas are the only known organisms where a retrovirus is transitioning from exogenous to endogenous. An exogenous retrovirus infects a host, inserts its genetic information into the cell’s DNA, and uses the host cell’s machinery to manufacture more viruses. When an exogenous retrovirus infects an egg or sperm cell and the viral genetic information is then passed down to the host’s offspring, the virus becomes an endogenous retrovirus (ERV).
Like humans, koalas have evolutionary defenses against endogenization.
“During the early stages of endogenization, there are huge numbers of retroviruses. KoRVs are present all across koalas’ genomes, with many thousands or tens of thousands of KoRVs in the population,” said Alfred Roca, a Professor of Animal Sciences and member of the Institute for Genomic Biology at the University of Illinois at Urbana-Champaign. “Over time most of them will disappear because these copies of the virus may be present in as few as one individual chromosome. If that one individual happens to not reproduce, or if it reproduces and the other chromosome is passed down, then that ERV will disappear.”
In order to end up with 100 ERVs in an organism, the species may have to start with 10,000 ERVs in its ancestors, Roca said. It takes retroviruses, like KoRV, many thousands of years to become a fixed part of the koala genome, like the eight percent of retroviral DNA that all humans share.
The ERVs that are successfully passed down are protected by the koala’s DNA repair mechanisms so that their rate of mutation is extremely low. Based on the dearth of mutations in the endogenous koala retroviruses, Roca’s team was able to estimate that the KoRVs integrated into the host germ line less than 50,000 years ago. “This is quite recent compared with other ERVs that are millions of years old and have accumulated mutations,” said first author Yasuko Ishida, a research specialist in Roca’s lab.
In koalas, KoRV has been linked to leukemia, lymphoma, and immune suppression, which can lead to increased susceptibility to chlamydia.
“It seems likely that for thousands of years since this virus integrated, the koala host has suffered fitness effects,” Roca said. “It is possible that across species, when a host lineage has been invaded by ERVs, it had to go through this process of adaptation between host and virus, which is a very sad finding. It may be a very long, slow, painful process for the host species, one which human ancestors have gone through and overcome many times in the distant past.”
In mammals, retroviral DNA is associated with placental development and has been found to protect hosts from harmful exogenous retroviruses.
“But once retroviruses become part of the host, they begin to help the host because that is how they survive,” Roca said. “They will be better off if they evolve to protect the host. Over time, the detrimental effects go down and the beneficial effects go up.”
In the 1900s, koalas were extensively hunted for their fur. In an effort to preserve koalas, a few individuals were moved to an island off the coast of Australia. Years later, the inbred island population was reintroduced to southern Australia. Today some of the southern koalas remain uninfected while almost all northern koalas have dozens of KoRVs in their genomes.
“Which is the lesser of two evils?” Roca said. “Do you try to conserve genetic diversity, which is present in the northern populations along with the retrovirus or do you conserve southern populations that don’t have the retrovirus but are horribly inbred?”
Roca’s research team included research specialist Yasuko Ishida, graduate student Kai Zhao, and scientific collaborator Alex Greenwood of the Leibnitz Institute in Berlin. Their work was supported by the National Institute of General Medical Sciences. The San Diego Zoo, Columbus Zoo, San Francisco Zoo, and Riverbanks Zoo provided the koala samples.
Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion Mol Biol Evol (2014) doi: 10.1093/molbev/msu275 First published online: September 25, 2014
Scientific summary from Pubmed:
Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In 3 wild southern Australian koalas, there were fewer KoRV loci than in 3 captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none were exogenous. Of the 39 endogenous KoRVs (enKoRVs), only 1 was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′ and 3′ long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of 10 enKoRVs, the 5′ LTR sequence was identical to the 3′ LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of ca. 22,200 to 49,900 years ago, although a much younger age is possible. Across the 10 proviruses, 7 LTR haplotypes were detected, indicating that at least 7 different retroviral sequences had entered the koala the germ line