Retrotransposons (known informally as “jumping genes”) are like viruses that are permanently encoded in a genome. They are genetic elements that can cause additional copies of themselves to be added to the genome. Because of this ability, they make up a large part of the noncoding (“junk”) DNA in a genome. About 42% of human DNA is active or inactive retrotransposons. In other mammals the percentage may be even higher. Even more of our genomes may represent traces of retrotransposon activity in the distant past.
As far as biologists can tell, retrotransposons generally serve no useful purpose. They exist, like parasites, simply because they can. However, the view that they have no use may need to be revised in light of new research. On the other hand, retrotransposon activity that isn’t adequately suppressed may be responsible for neurological diseases from dementia to Parkinson’s to schizophrenia, and perhaps cancer too.
Determination of whether human retrotransposons are beneficial or detrimental is yet to be made. All that’s now been shown, in the new research, is that retrotransposons are active in brain tissue, especially in parts of the brain responsible for learning and memory – specifically the hippocampus and the caudate nucleus.
Mobile DNA molecules that jump from one location in the genome to another may contribute to neurological diseases and could have subtle influences on normal brain function and behavior, according to a study published October 30 in Nature. …
Researchers from the Roslin Institute in Edinburgh, Scotland, have now comprehensively mapped retrotransposon insertion sites in the genomes of normal human brain cells for the first time.
They used state-of-the-art DNA sequencing technology to screen for retrotransposons in tissue samples taken postmortem from three individuals who were healthy when alive and had no neurological disease or signs of abnormality in their brain tissue. Focusing on two brain regions—the hippocampus and caudate nucleus—they identified nearly 25,000 different sites for the three main retrotransposon families.
How do retrotransposons work? Much like a retrovirus, such as HIV. A retrotransposon is encoded as normal DNA, and it can be transcribed into RNA in the usual way under suitable conditions. Once it is in the form of RNA, it can be converted back to DNA by a reverse transcriptase enzyme that is encoded in the DNA/RNA of the retrotransposon. (This is unlike normal messenger RNA, which is translated into proteins.) The new DNA can then be inserted elsewhere in the genome with an integrase enzyme also encoded in the retrotransposon.
Since it’s quite possible that retrotransposon DNA might be copied into the middle of essential genes, and thereby destroy them, there are cellular mechanisms that normally suppress retrotransposon transcription, by epigenetic means such as methylation or RNA inhibition. However, since significant retrotransposon activity is found (as the research demonstrates) in some brain cells, suppression of the activity may be relaxed if there’s some useful purpose – as yet unknown – to be served.
From the research abstract:
At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.