The emergence of life for the first time on this planet constitutes the classic question of what came first; the chicken or the egg?! Did a self-replicating DNA system occur before transcription or translation evolved (the DNA World) or did a self-replicating RNA system first emerge (the RNA world) or did self-replicating protein system first emerge (the Protein World)…or … let’s just leave it there for now.
This much is clear; DNA was an evolutionary afterthought. RNA served a dual function of Genetic Material as well as enzyme. This begs yet again another chicken egg problem! How could RNA’s role as a catalyst evolve, if there was nothing yet available to catalyze except RNA? The answer could be The Metabolism-First World, which even preceded RNA. But that is a different story for another time.
In brief, “Retroelements” are relics of the so-called ancient “RNA-world”! Their sequences represent more than half the human genome. Evolution is essentially a saga of subduing and eventually co-opting or rehabilitating Retrotransposons/Retroviruse jumping as a means of gene regulation. The hero of that story is a heroine named Barbara McClintock. (Everybody please stand up and please reverently bow your heads at the mere mention of her name!)
That said mobile elements directly can still cause three kinds of problems:
1. A functional gene is interrupted and no longer functional
2. A second copy of a gene is relocated to a different region of DNA, perhaps even a different chromosome. Expression of this gene is now subject to different regulation due to its new location creating all sorts of potential problems including gene dosage effects.
3. The transposition (especially the terminal repeats) may include enhancers which now activate neighboring genes inappropriately.
Mobile elements indirectly contribute to two kinds of other kinds of genetic disorder commonly clumped together as “indel”s, separately considered as inversion and deletion events. Actually, mobile elements can also contribute to a third type of genetic disorder called translocations.
Of course, everything that was identified as potentially problematic is also potential grist for evolution’s mill. Retroelements are undoubtedly the origin of introns and multiple promoters and enhancers in eukaryotes.
The generation of antibody and T-Cell receptor diversity is a direct consequence of co-opting Retrotransposons/Retroviruse jumping to rearrange the DNA before mRNA transcripts are even generated. Ditto the 800 genes in humans and 1400 genes in mice for olfactory receptors.
It is even possible that commitment steps in cellular differentiation similarly employ DNA rearrangement rendering precluding totipotency in certain cell lineages (at least some of the time).
François Jacob (of lac-Operon fame) once remarked that “Nature is a tinkerer and not an inventor…” new sequences are adapted from pre-existing sequences rather than created de novo. Domains are the common material used by nature to generate new sequences, they can be thought of as genetically mobile units in a fluid genome. Protein domains often correlate strongly with exons in multiple eukaryotic genomes and new genes emerge as a result of gene duplication and exon shuffling. It would appear that eukaryotic genomes are pretty fluid!
All of the above heralds the RNAi story, which in fact was discovered in bacteria first! CRISPR in Bacteria and DICER in Eukaryotes can also bind transcribed single-stranded RNAs that fold back on themselves to generate small regions of double-stranded RNA, those so-called “stem-loops” that allow a host cell to defend against any “retroelement”. Boy does this is all beginning to sound repetitive!
It now turns out that Bacteria can also take ‘RNA mug shots’ of threatening RNA-viruses! Life needed to defend itself against parasitic RNA before needing to defend itself against parasitic DNA. It was an easy bet to wager an RNA version of CRISPR would be discovered in bacteria. Sure enough, just check out the latest version of SCIENCE.