The above image is a segment of exon 4 from the human gene for the Oxytocin receptor (Oxtr). But this ain’t no ordinary exon. This particular segment is in fact a remnant of what is known as a LINE1 (L1) transposable element.
To “transpose” means to transfer from one place to another and so as you might infer, a transposable element is a segment of DNA which is capable of moving from one location in the genome to another, usually a nearby location. Transposable elements occur in two main forms, transposons and retrotransposons. A transposon is simply a segment of DNA that is capable of excising itself from its location within the genome and reinserting itself elsewhere. A retrotransposon, however, doesn’t actually excise itself but transcribes an RNA version which is subsequently used to reverse transcribe into its DNA form. That DNA then inserts itself into another segment of genome. This is basically how a retrovirus like HIV works.
About 50% of the human genome contains transposable elements, although the majority have mutated such that they are no longer capable of transposition or retrotransposition . There are four main categories of mobile elements in humans: the long interspersed elements (LINE), the short interspersed elements (SINE), the long terminal repeats (LTR) which also includes many retroviruses, and DNA transposons; all but the last category are retrotransposons. Only two subcategories remain transpositionally active in the human genome, the LINE1’s and Alu’s, the latter a remarkably successful SINE. You will often see SINE’s occurring in close relation to LINE’s because SINE’s are what are known as non-autonomous elements, meaning that they do not actually code for any gene products and are therefore dependent on latching onto a LINE in order to piggyback their way into the genome.
Using the Oxtr gene as an example, because this L1 has managed to latch itself onto the tail end of an exon (though it doesn’t actually overlap with any protein-coding sequence) we can easily see how our own cell’s transcription machinery has been exapted to transcribe an RNA copy of this L1 element. One can only wonder what this particular L1 transcript might be doing within the cell, for good, bad, or neutral. I have no doubt many such transcripts litter our cells, taking part in incalculable interactions. In future we’ll see whether that prediction stands the test of time.
I’m currently working on a paper involving transposable elements, focusing on how even extinct mobile content may be affecting genetic stability and confounding disease susceptibility. We have some very exciting results and I look forward to sharing them once we’re accepted for publication. However, what I can say now is that there do seem to be distinctly positive links between mobile element content and overall gene instability.
And I’ll leave you with that cliff hanger for now… 😉