A “domesticated” viral gene incorporated into the genome of mammals millions of years ago helps protect human embryos from infections, research in the journal Science suggests.
The viral envelope gene Suppressyn prevents embryonic viral infections by expressing a protein in the human placenta.
This counteracts vulnerabilities caused by an even older domesticated viral gene incorporated over 100 million years ago, which was essential for the emergence of the placenta during evolution.
That ancient viral genetic material created the Syncytin gene, which promotes the fusion of cells needed for placental function but also potentially exposes embryos to infection.
“This evolutionary innovation may have been key to the emergence, diversification, and success of placental mammals,” explain Ricky Padilla Del Valle and Richard N. McLaughlin Jr. from Pacific Northwest Research Institute in a perspective article accompanying the research.
“However, domestication of tools created by viral pathogens comes with an unavoidable cost.”
John A. Frank, from Cornell University, and colleagues conducted their study after noting the importance of identifying host factors that protect against viral infection.
Using computers, they screened the human genome and identified 1507 stretches of DNA sequence called open reading frames (ORFs) that could encode viral envelope proteins.
This was far more than previously appreciated, noted Del Valle and McLaughlin, and of these ORFs many exhibited tissue-specific transcription.
One of these was Suppressyn, and the researchers found it was expressed throughout human embryonic development, in contrast to many embryonic genes that are transcribed in specific developmental windows.
This indicated that it played a vital role in a cellular function, providing antiviral protection that is separate from the development of the embryo yet essential to it.
In addition, the alanine, serine, cysteine-preferring transporter 2 (ASCT2) receptor, which binds primate Syncytin-1, must be expressed to allow the formation of an essential placental barrier.
This barrier enables transfer of nutrients from maternal to fetal blood but prevents viruses accessing the fetus.
However, viruses that use Syncytin-1–like envelope genes can still recognize and bind ASCT2, and Suppressyn helps to counteract this unwanted effect as its encoded protein occupies the ASCT2 receptor.
“We predict the adaptive benefits of [envelope] ORFs to be generally transient, unless they have broader antiviral activity or gain additional cellular function,” the researchers say.
They speculate: “The human genome may hold many other retrovirus-derived proteins with protective effects against viral infection.”