“[The ENCODE scientists have] . . . reported the elephant in the room and then chosen to otherwise ignore it.” ~Prof. John Mattick, Director of the Garvan Institute of Medical Research.
Since September, scientists have been in an uproar following Ewan Birney’s promulgation of the ENCODE Consortium findings, stating that 80% of the human genome can be considered “biochemically functional”. From there, scientific journalists expounded with phrases like, “The Death of Junk DNA” and other such simplifications. In short, a poor way to present the nuances of genetics.
While a great number of molecular scientists have beaten down the findings with numerous and fervent protestations, ferociously attempting to claim back paradigms lost, I for one think that the elephant in the room is not only here to stay but that ten years down the line Ewan Birney’s faux pas will be looked upon more kindly. As a new generation of scientists inherit the laboratory, those who have not been so brutally brow-beaten with the Central Dogma of Biology but have instead been taught findings of the myriad RNA alongside the geneticist’s beloved protein, this new generation may be more willing to follow unwandered avenues wherever their data may lead.
I personally believe a new paradigm shift is coming. The trend has grown over previous years as more and more papers litter the search engines proclaiming more and more functions of various ribozymal transcripts, and finally with the results of the ENCODE Consortium I think we are marking a new era. Already it was admitted by even the stubbornest of opponents that:
“… vast portions of the genome are transcribed into RNA. A small amount of that RNA encodes protein, and some serves a regulatory role…” 
Ah, but what’s interesting is that it goes on to say that:
“… the rest of it is chock-full of seemingly nonsensical repeats, remnants of past viruses and weird little bits that shouldn’t serve a purpose.”
Shouldn’t they? Let’s take the case of retroviruses: even though their gene products may not be in the interest of their host, they still nevertheless may serve a purpose. And such transposable elements (TE) have been with us for millions, if not billions, of years. These elements, whether originally foreign or native, have developed ways for transposition; who is to say that even in the case of extinct elements which are no longer able to retrotranspose or transcribe functional copies of themselves, that their mutated gene products do not still have some regulatory function, either to the benefit of the TE’s themselves or some gene product our own cells have taken advantage of? In fact, many of those TE’s have provided the precise regulatory elements which these scientists so often study. How many enhancers have been born out of extinct mobile elements? Answers to these questions are still in their infancy and they are by no means studied by the majority of genetic scientists, which is truly a tragedy. To be literally blind to elements which may be vital to present-day cellular life and which also undoubtedly contributed to its evolution. True, a given scientist can’t be an expert in every field of life science, but for only such a small community of scientists to be studying mobile elements is a true crime.
Mobile elements aside, let’s rewind the tape even further to the early forms of life, proto-life. Even though many Origins of Life scientists support the theory that the first form of self-replication centered around RNA, not DNA, it’s currently unknown whether RNA was indeed the first form of life. Nevertheless, it was certainly an early form of life. (For more, see Gilbert, 1986, Nature, 319, 618 for starters.)
So picture this: you have an early form of proto-life which contains not a DNA genome but an RNA genome. At first you might think such an image well and good but then you realize a problem: How does this RNA replicate itself? In current cellular machinery, even within the circular double helices of prokaryotes, transcription is dependent upon not just the available genetic template but enzymes. Well, crap. There goes the RNA World Theory. –But wait! You suddenly remember that Frank Westheimer discovered back in 1986 that certain RNA transcripts are capable of possessing enzymatic qualities. Brilliant! And since that time, more and more scientists have reported similar findings .
What’s the point of my reviewing RNA World Theory? If our cells truly were originally based off of RNA and only later began producing protein products which in some cases may have succeeded the function of previous ribozymal transcripts, then it is quite rational to conclude that RNA transcription is deeply rooted into the foundation of our cellular makeup. Would it then be surprising to find that, not only a large portion of the genome is transcribed, but a surprising portion may serve some biochemical function?
I have taken the time to look at a variety of genes in my work, to pick them apart nucleotide by nucleotide, to locate remnants of transposable elements within them, to see the relationship of their exons, introns, and promoters, to mark every potential CpG island and its relationship to these other elements. And while there is an incredible degree of repetition (that in itself a fascination of mine), patterns begin to emerge. The relationship between different mobile elements and the segment of genome they had originally targeted for insertion, it’s not random and I don’t believe it’s solely demarcated by a few specific local nucleotides either. I can’t yet support it with hard data (although I’m currently working on it), but I do honestly suspect that there is a rhyme and a reason to the conformation of the genome, just as much as there’s purpose in the primary sequence of proteins which give rise to particular functional secondary and tertiary conformations.
I should state that I believe the overall structure of the local and semi-local DNA is what gives it its function. Within reason, mutations may occur which do not adversely affect production of a given gene, provided key single nucleotides are not targeted. But even the insertion or deletion of a few trinucleotides can forever change whether a gene product is transcribed and make the difference between a stable and unstable region.
In my view, Genetics requires a more holistic approach than has previously been applied. We must study primary structure alongside secondary and tertiary topologies; we must continue to study RNA both as transcript and enzyme; we must study active and extinct mobile elements within the genome and how they relate to overall DNA topology and potentially affect transcription; and for those scientists who wish to understand not just the how but the why, we must better acquaint ourselves with Origins of Life research. Not every problem can be solved by the information before us. Sometimes we need to look backwards to find a reason.
This entry is a combination of science and editorial, heavier on the editorial, but every person must decide for themselves. And I realize that not all– perhaps even the majority– agree with my views. But were you to ask me whether I consider intergenic and intronic regions as “junk”, I would answer a resounding “NO”.
Junk DNA is this scientist’s treasure.
Pingback: Professional Publications & Positions « Emily L. Williams – Curriculum Vitae·