A recent article in ScienceDaily based on a publication in the journal Cell Reports describes a hot topic in neurobiology: the contribution of endogenous retroviruses (ERVs) towards human brain development (1,2). Perhaps the most famous retrovirus is HIV, the Human Immunodeficiency Virus, shown in Figure 1. Unlike HIV, however, ERVs are non-pathogenic. Moreover, a large percentage of our DNA—about 10%—is constituted by retroviruses that have gradually found their way into our genome over millions of years of evolution (1,2). Previously, the ERV portion of our DNA was long considered useless and termed “junk DNA”. In this study, senior author Johan Jakobbson and his group show that the ERVs incorporated in our genome are not useless. In fact, the thousands of retroviruses inherent in human DNA alter gene expression, influence brain development, and contribute to the expression of neurological diseases.
Endogenous retroviruses constitute a greater proportion of our genome than genes that control protein production, which comprise only 2% of our DNA. Researchers working in Dr. Jacobsson’s group reported in a new discovery that the DNA made of ERVs also influences the production of proteins, albeit indirectly (1,2). The thousands of retroviruses embedded in our DNA are docking platforms for a protein called TRIM28. The researchers discovered that besides repressing retroviral DNA, TRIM28 can regulate expression of standard genes that lie adjacent to retroviral DNA. Thus, via the TRIM28 mechanism, retroviral DNA indirectly controls the expression of normal human DNA expression.
ERV DNA exists in different places in different individuals’ genomes, so the switching-off mechanism affects different people differently, making ERVs tools for introducing genetic diversity.
Retroviruses in humans are very different from retroviruses in other species, besides gorillas and chimpanzees, who are our closest relatives from evolutionary history. Prior studies on retroviral DNA incorporated into host DNA were often done in mice. The applicability of these prior studies to humans was limited, but the recent study reported by Dr. Jacobsson’s group was done with human cells (1,2). These investigators concluded that since ERVs influence gene expression through the TRIM28 mechanism, a phenomenon that is particularly apparent in brain cells, ERVs affect the development of the human brain.
- Lund University. “Viruses in genome important for our brain.” ScienceDaily. ScienceDaily, 12 January 2017. <www.sciencedaily.com/releases/2017/01/170112110840.htm>.
- Per Ludvik Brattås, Marie E. Jönsson, Liana Fasching, Jenny Nelander Wahlestedt, Mansoureh Shahsavani, Ronny Falk, Anna Falk, Patric Jern, Malin Parmar, Johan Jakobsson. TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells. Cell Reports, 2017; 18 (1): 1 DOI: 1016/j.celrep.