The sex of all mammalian babies, including people, may be determined by a simple modification of a virus that insinuated itself into the mammalian genome as recently as 1.5 million years ago.
“Why mammalian sex ratios are determined by a remnant of ancient virus is a fascinating question.”
“Basically, these viruses appear to allow the mammalian genome to continuously evolve, but they can also bring instability,” says Andrew Xiao of the genetics department at Yale University. “Aside from the embryo, the only other places people have found this virus active is in tumors and neurons.”
In a recent paper published in the journal Nature, researchers describe a mechanism by which the early embryo turns off this virus on the X chromosome, which ultimately determines the sex of an organism. If the level of this molecular marker is normal, X chromosomes remain active, and females and males will be born at an equal ratio. If the marker is overrepresented, X chromosomes will be silenced, and males will be born twice as often as females.
“Why mammalian sex ratios are determined by a remnant of ancient virus is a fascinating question,” Xiao says.
[Female cells use RNA to turn off X chromosome]
Tens of millions of years ago viruses invaded genomes and duplicated themselves within the DNA of their hosts. Researchers estimate that more than 40 percent of the human genome is made up of such remnants of viral duplications.
In most cases, these remnants remain inactive, but recently scientists have discovered they sometimes take on surprising roles in developing embryos and may even push mammalian evolution. The virus active in the mouse genome that influences sex ratios is relatively recent—in evolutionary terms—and is enriched on the X chromosome.
The researchers found the mechanism that disables the virus and say the newly discovered modification in mammals is a surprising expansion of the epigenetic toolbox. Epigenetics modulates gene expression during development without actually altering the sequences of genes.
In the new marker, a methyl bond is added to adenine—one of the four nucleotides that comprise base pairs in DNA—allowing it to silence genes. For decades, most researchers assumed that a modification of the nucleotide cytosine was the only form of gene silencing in mammals.
It’s possible that this mechanism might also be used to suppress cancer, which has been known to hijack the same virus to spread. Further, in other organisms, such as C. elegans and the fruit fly Drosophila, the mechanism plays an entirely opposite role and activates genes, not suppresses them.
“Evolution often uses the same piece but for different purposes and that appears to be the case here,” Xiao says.
The National Institutes of Health funded the work.
Source: Yale University
