Koala genes used to study human genome

Scientists are constantly finding ways to better understand the intricacies of human DNA. A recent study has investigated the presence of endogenous retroviruses present in the human genome. 

Endogenous retroviruses (ERVs), which make up about eight percent of the human genome, are DNA sequences that were derived from and still resemble retroviruses. A virus becomes an ERV when it infects a gamete, and the viral information is integrated into the cell and can be passed down from one generation to another.

As the retrovirus enters the host cell’s cytoplasm, it will use its own reverse transcriptase enzyme to create DNA from its RNA material. The DNA is then incorporated into the host cell genome, where the cell’s machinery is used to assemble more copies of the virus.

This process of incorporating the ERVs from an outside source into a stable component of the genome is a long and random one, as many of the ERVs are lost in the process of passing on the genetic information to an offspring. A species may have to start out with 10,000 ERVs just to end up with a constant amount of 100 of the viruses in the genome — a process that can take up to thousands of years.

ERVs are common in all vertebrate genomes, and most species have already completed the process of adapting these ERVs from their origins. The only exception to this is the koala, whose retrovirus (KoRV) is still in the process of transitioning to its endogenous form. This makes koalas ideal candidates for a study: Scientists can observe the endogenization process as it happens and make inferences about the ERVs already present in the human genome. 

This is precisely what Alfred Roca, an Animal Sciences professor at the University of Illinois at Urbana-Champaign, and his research team set out to do. In their study recently published in the Oxford Journals’ Molecular Biology and Evolution, Roca and the other researchers identified 39 distinct KoRVs as endogenous — that is, retroviruses that are passed down from either parent. Only one of the 39, however, originated from both parents. This indicates that the retroviral endogenization is still in the initial part of its process, as the ERVs are proliferated at low frequencies from large numbers.

For the ERVs that do get passed down, koalas have an inbuilt DNA repair mechanism. This keeps the rate of mutation very low. As a result, Roca’s team was able to estimate it was about 50,000 years ago when the KoRVs were first integrated into the koala’s germ line. This is relatively recent in comparison with other species, which have ERVs that are more than a million years old and have accumulated mutations over time.

The endogenization process of the retrovirus is not without some consequence on the koalas. According to Roca, it is likely that the koala host has suffered a decrease in fitness since the thousands of years that the virus has been integrated. The adaptation process between the host and the newly internalized virus is not a smooth one and can be painful for the host — something our human ancestors have experienced multiple times in the past. 

However, the retroviruses are not always detrimental to the hosts. As the virus gradually becomes a part of the host, it evolves characteristics that are beneficial to not only itself, but also, in effect, the host. For example, in mammals ERVs are associated with placental development and the protection of the host against other harmful exogenous viruses. At the end of the day, the advantages of having an ERV outweigh the costs, thus ensuring this trait is passed on from generation to generation.