Up to eight percent of our DNA is viral in origin. These ancient fossils of our ancestors’ infections are both parasitic, linked with a whole host of diseases, and symbiotic in nature. The latter part of this message now seems to be clearer than ever, with the discovery that these remnants are critical for human development.
Published in Nature Genetics, scientists from Stanford University discovered that molecules originating from these viral sequences are required for early embryo cells to acquire the ability to generate the cells that ultimately make up the body. Without them, embryonic development comes to a standstill very early on.
“We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit,” study author Vittorio Sebastiano said in a statement. “In this manner, they may have even contributed species-specific characteristics and fundamental cell processes, even in humans.”
How a single fertilized egg goes on to become an entire body is through the acquisition of a property called pluripotency: the ability of a cell to transform into any other type belonging to an organism. Scientists have managed to bestow non-pluripotent cells in the lab with this property by bathing them in a cocktail of specific molecules present very early on in the development, but the finer details of this process remained hazy.
More specifically, scientists have found that molecules of RNA – DNA’s chemical cousin – play a crucial role. DNA is a template for RNA, strands of which can then either be used to direct protein synthesis or for a variety of other roles in the cell, including modulating the expression of genes.
These molecules are not modest in number in the cell, so to narrow their search the team began by looking at those that are specific to embryonic stem cells, leading to the discovery of 146 such sequences. To whittle this down even further, they focused on those that were most strongly expressed. Of the resulting 23, named HPAT1-23, 13 predominantly comprised sequences from a well-known family of viral elements collectively known as HERV-H.
Long ago, these stretches of genetic material were a type of virus called a retrovirus, the same family to which HIV belongs. Part of their life cycle involves slotting their genome into that of the host so that the infected individual inadvertently ends up copying the virus’ genetic material along with their own. If such an event happens to occur in an organism’s germ line – their sperm or egg cells – then the sequence can be inherited by future generations.
Although most of these sequences have acquired so many mutations over time that they are effectively defunct, some can be expressed and even result in the production of virus-like particles. Looking for those that are expressed very early on in development, during the blastocyst phase, three HPATs piqued the interest of the researchers: 2, 3, and 5. These, they discovered, display high expression levels within the region of the blastocyst that goes on to become the fetus.
Further examination revealed that these molecules interact with a family of small RNAs called let-7, which is associated with pluripotency and development transitions. Corroborating their roles in development, the scientists found that blocking them in specific cells of a developing embryo prevented these from going on to form the mass of cells that ultimately becomes a fetus.
“What’s really interesting,” said Sebastiano, “is that these sequences are only found in primates, raising the possibility that their function may have contributed to unique characteristics that distinguish humans from other animals.”