Genes 2 Brains 2 Mind 2 Me

For more than a decade, we’ve known that at least 95% of the human genome is junk – or junque – if you’re offended by the thought that “you” emerged from a single cell whose genome is mostly a vast pile of crap – or crappe – if you insist.  Hmmm, what is this crap?  It turns out to be a lot of random repeating sequences and a massive collection of evolutionary artifacts left over from the evolution of earlier genomes – mainly bits of retroviruses who once inserted themselves irreversibly into our ancestors’ genomes.  One subset of this type of – can we upgrade it from crappe to “relic” now? – is something we’ve labelled “autonomously mobile DNA sequences” or more specifically, “long interspersed nuclear elements (LINEs or L1s)”.  This class of DNA relic comprises more than 15% of the human genome (that’s about 3-5x more than the relevant genomic sequence from which you emerge) and retains the ability to pick itself up out of the genome – via an RNA intermediate – and insert itself into new places in the genome.  This has been observed to happen in the germ line of humans and a few L1 insertions are even responsible for genetic forms of humn disease (for example in the factor VIII gene giving rise to haemophilia).  The mechanism of transposition – or “jumping” as these elements are sometimes called “jumping genes” – involves the assembly of a certain type of transcriptional, transport and reverse-transcription (RNA back to DNA) apparatus that is known to be available in stem cells, but hardly ever  in somatic cells.

Except, it would seem, for the brain – which as we’ve covered here before – keeps its precious neurons and glia functioning under separate rules.  Let’s face it, if a liver cell dies, you just replace it without notice, but if neurons die, so do your childhood memories.  So its not too surprising, perhaps, that brain cells have special ‘stem-cell-like’ rules for keeping themselves youthful.  This seems to be borne out again in a paper entitled, “L1 retrotransposition in human neural progenitor cells” by Coufal et al., [doi:10.1038/nature08248].  Here the team shows that L1 elements are able to transpose themselves in neural stem cells and that there are more L1 elements (about 80 copies more per cell) in the hippocampus than in liver or heart cells.  So apparently, the hippocampus, which does seem to contain a niche of stem cells, permits the transposition or “jumping” of L1 elements in a way that the liver and heart do not.  Sounds like a fun place to be a gene!

Read Full Post »