Almost half of the human genome is made up of transposable elements (TEs). I’ve always been fascinated (and amazed) by this fact, partly because it seems dangerous and messy. This is because it IS dangerous and messy: TEs are essentially all viruses, capable in principle of being reanimated to do what they love to do, which is invade other parts of a genome. When they do this, they can (and do) cause damaging mutations. That’s one way they can blow up a perfectly good cell or embryo; another way is to destabilize the genome through their interactions with other TEs (numbering, let’s remember, in the millions). And so, multiple molecular systems are devoted to suppressing the activity of these parasites. (This must be annoying to the intelligent designers who wove the genomes together, but that’s a topic for the “Argument Clinic.”)
But wait, there’s another way that a retroelement (fancy word for a retrovirus-like parasite in a genome) can cause suffering and chaos, just reported this month in Nature Genetics. Paper is open access.
Abstract:
Transposable elements (TEs) are scattered across mammalian genomes. Silencing of TEs prevents harmful effects caused by either global activation leading to genome instability or insertional mutations disturbing gene transcription. However, whether the activation of a TE can cause disease without directly affecting gene expression is largely unknown. Here we show that a TE insertion can adopt nearby regulatory activity, resulting in the production of cell-type-specific viral-like particles (VLPs) that affect embryo formation. Failure to silence an LTR retrotransposon inserted upstream of the Fgf8 gene results in their co-expression during mouse development. VLP assembly in the Fgf8-expressing cells of the developing limb triggers apoptotic cell death, resulting in a limb malformation resembling human ectrodactyly. The phenotype can be rescued by mutating the retrotransposon coding sequence, thus preventing its full endogenous retroviral cycle. Our findings illustrate that TE insertions can be incorporated into the local genomic regulatory landscape and that VLP production in post-implantation embryos can cause developmental defects.
The paper shows that a certain TE can get itself expressed (activated) by tagging along with legit genes (a limb-development gene in this case, Fgf8) and then actually make viral particles that then cause massive cell death.