Here's what Athena Andreadis has to say on the Scientific American website: Junk DNA, Junky PR. Athena is a professor in the Department of Cell and Developmental Biology at the University of Massachusetts Medical School.
A week ago, a huge, painstakingly orchestrated PR campaign was timed to coincide with multiple publications of a long-term study by the ENCODE consortium in top-ranking journals. The ENCODE project (EP) is essentially the next stage after the Human Genome Project (HGP). The HGP sequenced all our DNA (actually a mixture of individual genomes); the EP is an attempt to define what all our DNA does by several circumstantial-evidence gathering and analysis techniques.That's exactly right, Athena! The PR campaign was deliberate and misleading and it's true that most science journalists were ill-prepared to write about junk DNA.
The EP results purportedly revolutionize our understanding of the genome by “proving” that DNA hitherto labeled junk is in fact functional and this knowledge will enable us to “maintain individual wellbeing” but also miraculously cure intractable diseases like cancer and diabetes.
Unlike the “arsenic bacteria” fiasco, the EP experiments were done carefully and thoroughly. The information unearthed and collated with this research is very useful, if only a foundation; as with the HGP, this cataloguing quest also contributed to development of techniques. What is way off are the claims, both proximal and distal.
A similar kind of “theory of everything” hype surrounded the HGP but in the case of the EP the hype has been ratcheted several fold, partly due to the increased capacity for rapid, saturating online dissemination. And science journalists who should know better (in Science, BBC, NY Times, The Guardian, Discover Magazine) made things worse by conflating junk, non-protein-coding and regulatory DNA.
Let’s tackle “junk” DNA first, a term I find as ugly and misleading as the word “slush” for responses to open submission calls. Semantic baggage aside, the label “junk” was traditionally given to DNA segments with no apparent function. Back in the depths of time (well, circa 1970), all DNA that did not code for proteins or proximal regulatory elements (promoters and terminators) was tossed on the “junk” pile.Oops! That's not quite true. Back then we knew about tRNA genes, ribosomal RNA genes, origins of replication, and centromeres. It wasn't long before we learned about introns, small functional and regulatory RNAs, and telomeres.
However, in the eighties the definition of functional DNA started shifting rapidly, though I suspect it will never reach the 80% used by the EP PR juggernaut. To show you how the definition has drifted, expanded, and had its meaning muddied as a term of art that is useful for everyone besides the workaday splicers et al who are abreast of trendy interpretations that may elude the laity, let’s meander down the genome buffet table.Hmmm ... this could get interesting. It still looks to me like 90% of the genome is junk [What's in Your Genome?]. I didn't see any rapid shifting the the 1980s. Let's see where this is headed.
Protein-coding segments in the genome (called exons, which are interrupted by non-protein-coding segments called introns) account for about 2% of the total. That percentage increases a bit if non-protein-coding but clearly functional RNAs are factored in (structural RNAs: the U family, r- and tRNAs; regulatory miRNAs and their cousins).Okay, we may have known about some of those things in the 1970s but I'll acknowledge that we learned lot's more in the 1980s. What I won't acknowledge is that we can assign function to 25% of our genome. Where does that number come from?
About 25 percent of our DNA is regulatory and includes signals for: un/packing DNA into in/active configurations; replication, recombination and meiosis, including telomeres and centromeres; transcription (production of heteronuclear RNAs, which contain both exons and introns); splicing (excision of the introns to turn hnRNAs into mature RNAs, mRNA among them); polyadenylation (adding a homopolymeric tail that can dictate RNA location), export of mature RNA into the cytoplasm; and translation (turning mRNA into protein).
All these processes are regulated in cis (by regulatory motifs in the DNA) and in trans (by RNAs and proteins), which gives you a sense of how complex and layered our peri-genomic functions are. DNA is like a single book that can be read in Russian, Mandarin, Quechua, Maori and Swahili. Some biologists (fortunately, fewer and fewer) still place introns and regions beyond a few thousand nucleotides up/downstream of a gene in the “junk” category, but a good portion is anything but: such regions contain key elements (enhancers and silencers for transcription and splicing) that allow the cell to regulate when and where to express each protein and RNA; they’re also important for local folding that’s crucial for bringing relevant distant elements in correct proximity as well as for timing, since DNA-linked processes are locally processive.Well, I'm one of those biologists who think that most intron sequences are junk [Junk in Your Genome: Intron Size and Distribution]. And I'm one of those biologists who think that regulatory sequences are usually near the genes they regulate and don't take up a lot of DNA sequence [Junk in Your Genome: Protein-Encoding Genes].
The expression of a typical gene may be controlled by the binding of a dozen or so activators and repressors but the minimal amount of DNA required for their proper function isn't much more than 1000 bp. or so. The fact that they may be spread out over several thousand base pairs interspersed with dead transposons and other flotsam doesn't mean that all the DNA is functional.
But what of the 70% of the genome that’s left? Well, that’s a bit like an attic that hasn’t been cleaned out since the mansion was built. It contains things that once were useful – and may be useful again in old or new ways – plus gewgaws, broken and rusted items that can still influence the household’s finances and health… as well as mice, squirrels, bats and raccoons. In bio-jargon, the genome is rife with duplicated genes that have mutated into temporary inactivity, pseudogenes, and the related tribe of transposons, repeat elements and integrated viruses. Most are transcribed and then rapidly degraded, processes that do commandeer cellular resources. Some are or may be doing something specific; others act as non-specific factor sinks and probably also buffer the genome against mutational hits. In humans, such elements collectively make up about half of the genome.I agree with the gist of this description but I would never say that junk DNA is "subject to evolutionary scrutiny." By my definition, junk DNA has no function and it should be evolving at the rate expected of neutral DNA (i.e. the mutation rate). In fact, that's what the data shows.
So even bona fide junk DNA is not neutral and is still subject to evolutionary scrutiny – but neither does every single element map to a specific function. We know this partly because genome size varies very widely across species whereas the coding capacity is much less variable (the “C-value paradox”), partly because removal of some of these regions does not affect viability in several animal models, including mice. It’s this point that EP almost deliberately obfuscated by trumpeting (or letting be trumpeted) that “junk DNA has been debunked”, ushering in “a view at odds with what biologists have thought for the past three decades.”
All in all, this is a good article because it focuses on the fact that the ENCODE results were misinterpreted by the consortium and by the press.
The EP results are important and will be very useful – but they’re not paradigm shifters or miracle tablets and should not pretend to be.