Viral fossils that integrated into our genetic code millions of years ago could be responsible for some subtypes of autism, a new study has suggested. Experiments in mouse models revealed a possible role for these endogenous viral elements and suggest that this should be an avenue for further research.
The human genome is littered with sequences derived from viruses that infected our ancient ancestors. Called endogenous retroviruses (ERVs), these genetic elements make up about 8 percent of our genome, and originated from the ancestors of modern retroviruses like HIV.
Most of the time, ERVs remain dormant, silenced by the body’s sophisticated regulatory machinery. There have been tentative claims that these sequences could be involved in some cases of sporadic amyotrophic lateral sclerosis (ALS); there is also some evidence to suggest that they may play a protective role during embryonic development. Overall, though, they remain largely mysterious relics of our genetic history.
A new study, from an international team led by researchers at Kobe University in Japan, has uncovered a possible role for ERVs in the development of autism.
The experiments were performed using a mouse model of idiopathic autism – that’s autism with no known genetic or environmental cause. Brain scans on two different but related strains of mice, called BTBR/J and BTBR/R, revealed structural differences in 33 brain regions. The most stark was in the corpus callosum, the bundle of nerves that connects the two hemispheres of the brain together.
Further investigations revealed that the BTBR/R mice had significantly higher levels of ERVs compared with non-autistic mice, and genetic analysis suggested that these ERVs had been activated. The authors suggest that this is down to a failure of the mechanisms that usually keep ERVs sitting quietly in the genome, and found that the activation led to increased copy number variants (CNVs) – repeated genetic sequences that vary in number between individuals – in the autistic mice. The study concluded that ERV activation during fetal development could increase the likelihood of autism.
The team also performed extensive behavioral tests on their two different groups of autistic mice. BTBR/R mice displayed less anxiety than the BTBR/J mice. They also performed almost as well as neurotypical mice in a maze test (similar to the one in the video below), showing they have a near-typical level of spatial learning ability. However, the BTBR/R mice also showed more repetitive behaviors and less willingness to interact socially with other mice, which the researchers refer to as the “core symptoms” of autism.
Links between the corpus callosum and autism have been made before. However, what the researchers found intriguing here was that the BTBR/R mice – which had more of the classical autistic behavioral traits – actually had a typical corpus callosum, according to their brain scans.
Therefore, even though these two mouse strains have shared ancestry, they show distinct differences in both brain structure and behavior.
The authors suggest that BTBR/R, which is the lesser-used mouse model, is actually a more accurate representation of idiopathic autism, and could therefore be important for future study.
They also point to the need for further research into how ERV activation could predispose individuals to developing autism, particularly in the light of previous research that has found distinctive human ERV signatures in autistic people. It is hoped that, in the future, scientists may be able to build a better classification system for the different types of autism.
“Taken together with the demonstrated roles of ERV in CNV formation, our observation of the two BTBR strains provides a vivid model to describe how the genome evolves toward [autism] susceptibility,” the study concludes.
The study is published in Molecular Psychiatry.
Source Link: Ancient Viruses Could Be Drivers Of Autism, New Research Suggests
