6mA(ce) in the hole. m6-A is utilized by the cells to curb the activities of young active transposons on ChrX (green lines). Kristin Robertshaw, Pacific Biosciences

The remnant of an ancient virus DNA on the sex chromosome in mammals has been found to influence the sex ratio, with an overrepresentation of it causing twice as many males to be born as females. The virus is among the many others that has insinuated itself into the human genome over a million years ago.

The Yale University team found a mechanism by which the embryo turns off the virus on the X chromosome. When the level of this virus DNA fragment on X is normal, the chromosome remains active and females and males are born in equal ration. However, if it is high then the X chromosome is silenced and more males are born.

Besides the embryo, this virus is active in tumours and neurons.

"Basically, these viruses appear to allow the mammalian genome to continuously evolve, but they can also bring instability," said Andrew Xiao of the Department of Genetics and Yale Stem Cell Center, senior author of the paper published online March 30 in the journal Nature.

In the co-evolution of humans and viruses, the virus-generated DNA was copied and passed along down generations leading to a significant percent of human DNA coming from viruses. Most often these fragments are inactive. But as in the present finding, they seem to play some important roles in mammalian evolution. The virus influencing sex ratio in mouse models was a relatively recent one and was enriched on the X chromosome.

The Yale-led team found the mechanism that disables the virus and this came as a surprise in a modification of the adenine nucleotide by adding a methyl bond. It was believed that modification of cytosine alone caused gene silencing in mammals. Such epigenetics modifies DNA by turning on or off certain genes without actually altering the sequences of genes.

This modification could also be possibly used to suppress cancer, which has been known to hijack the same virus to spread, said Xiao. In other organisms, such as C elegans and the fruit fly Drosophila, this mechanism plays an entirely opposite role by activating genes instead of suppressing them.

Pacific Biosciences of Menlo Park provided the technology used in the discovery.

The human DNA has borrowed genes from many other species, owing to common ancestors dating back to million years. Last year, biologists from the University of Texas at Austin showed that hundreds of genes from a common ancestor live on nearly unchanged in yeast and humans. The human genome and that of the chimp's match to around 96 percent.
