I've tried to make this accessible, so I'll need double forgiveness. My medical school readers, pardon me for explaining what DNA does... again. I know you're paying attention in MoBio. For my non-med school readers, I apologize for all the jargon I don't know is jargon. If anything is unclear, please tell me so I can remember how normal humans talk outside of the kingdom of Medschoolandia.
I know it's long, but comments would be much appreciated.]
As you probably know DNA is our code. We used to think that DNA only coded for protein. Proteins are the machines in our cells which do everything from contract our muscles to filtering our blood and everything in between. We have about 25,000 proteins encoded in our body to do every conceivable function. The strange part is that these protein coding sequences are only a few percent of the total genome. The mystery thirty years ago was: why do we have a 3 billion-letter code when we only need 60 million for proteins?
The initial answer came from the theory of evolutionary. If we evolved by random and accidental processes, it is reasonable to believe that seemingly useless codes are actually useless, vestigial organs or genetic fossils. If there were no designer concerned about the elegance and efficiency of his code, then one ought not expect elegance.
This was formally postulated in the early years of DNA sequencing. This view was first offered by Susuma Ohno who wrote in a 1972 article titled So Much ‘Junk DNA’ in our Genome, “Our view is that [junk DNA segments] are the remains of nature’s experiments which failed. The earth is strewn with fossil remains of extinct species; is it a wonder that our genome too is filled with the remains of extinct genes?”
This was the dogma for almost three decades. Searching the literature (ISI Web of Knowledge; a database of most of the peer-reviewed science writing) for the phrase “Junk DNA,” one finds it used initially in 1972, then used throughout the 80’s and 90’s. Scientists built their theories on it and operated under the assumption that the ‘junk’ was useless.
One group even made a computer simulation to prove that evolution predicts junk DNA. In an article in the journal Science (one of the two superpowers in the scientific world) “Computer Genome'' Is Full of Junk DNA the author writes, “The simulation clearly shows that eukaryotic genomes…will evolve to a large size most of which sequences are vestigial in some way” (everything more advanced than a yeast cell is ‘eukaryotic,’ including humans). He continues to say that, “Most of the DNA in eukaryotic genomes…did nothing at all.” Then he waxes poetic to conclude, “Molecular maps … of DNA are characterized by islands of transcribed sequences [proteins code] in a sea of silent DNA.” This captures the mood of the era.
As an aside, there is something you should know about biologists: they, like most scientists, are loathed to challenge dogma (It surprised me to find that they actually admit to this diction in scientific papers and say things like “…consistent with the postulate of the ‘central dogma,’” and “…without infringing Crick's central doctrine…”). There were very early, weak suggestions that junk DNA might have some purpose (when you screw it up, it screws up the animal), but nothing to speak of until the 90’s.
The first explicit attack on the Junk DNA notion wasn’t from a biologist (who, above all else, seemed terrified of boat-rocking), but a cryptographer named Simon Shepherd. He figured, “nature would not go to all that trouble [to copy junk DNA] without reason.” In 1993, he used signal analysis to guess at a purpose for junk DNA. His conclusion, with absolutely no background in biology and analyzing only sections of the genome (the human genome project wasn’t finished yet), was that the non-coding sections between genes was an error correcting code making sure that proteins came out properly (The cryptographer who took a crack at 'junk' DNA. New Scientist, 26 June 1993; it turns out that he correctly guessed one of the purposes of it). Though significant historically speaking, the journal he published in doesn’t have much say in where science goes.
Quiet support for the theory of useful junk built up in the late 80’s and early 90’s, but no one openly and seriously challenged the term ‘junk DNA,’ at least not in the scientific literature. Then finally in 1994 a pair of articles in Science challenged, for the first time in the mainstream scientific literature, the notion of Junk DNA (“Mining Treasure from ‘Junk DNA,’” Vol. 263, No. 5147 pp. 608-610 published in February and “Hints of a Language in Junk DNA,” Vol. 266. no. 5189, p. 1320 published in November). In the earlier article, several possible functions of non-coding DNA were suggested by reputable researchers, (who published their work without using the term ‘junk DNA’). The article concludes with this: “Enough gems have already been uncovered in the genetic midden to show that what was once thought to be waste is definitely being transmuted into scientific gold.” The latter article concludes with a quotation from the Harvard biologist Walter Gilbert, “I think what we call ‘junk DNA’ will have a number of uses.”
1994 was the year the dam broke. Once there was mainstream support for “Junk DNA,” biologists jumped right on the bandwagon. Once Science said it was OK to say that Junk DNA had a purpose, many articles were published to that effect. Throughout the 90’s and into the new millennium, people began to find role after role for junk DNA. Everyone was bashing Junk DNA starting 1994 and lasting a decade. Here is a brief history of article titles throughout the years:
1972 - “So Much ‘Junk DNA’ in our Genome,” Brookhaven Symposium on BioLOGY
1986 - “’Computer Genome’ Is Full of Junk DNA,” SCIENCE
1994 - “Hints of a Language in Junk DNA” SCIENCE,
1998 - “Should scientists scrap the notion of junk DNA?,” J. NAT’L CANCER INSTITUTE
2006 - “Regulatory RNAs and the demise of 'junk' DNA,” GENOME BIOLOGY
In 2006, it seemed that people finally realized that the junk DNA horse was actually dead, and whipping it was no longer nearly as much fun as had been in the late 90’s. Unfortunately the term ‘junk DNA’ proved too sticky and did not un-stick, even to this day (people call it ‘junk DNA’ believing it has a purpose… that’s the trouble with catchy nicknames). It is interesting to notice the time gap between 1994 and 2006. In a little over a decade we went from ‘A hint of language’ to the ‘demise of junk DNA.’
Now it is believed that non-coding sequences may even be more important than the actual ‘coding’ regions. We have seen non-coding DNA control how proteins are expressed. In other words, non-coding DNA tells the cell how much protein to make. If the coding DNA is like the blueprint for a car, the non-coding DNA is the factory foreman telling deciding to make 1000 cars instead of 10). The non-coding DNA that does this is sometimes immediately around a code, sometimes interspersed between the code, and sometimes even tens of thousands of letters away (like a boss in New York ordering the Detroit factory to slow down production). We’ve seen RNAs which don’t ever turn into proteins further regulating things and doing things we thought only proteins could do. The “Crick Doctrine” and every other dogma we held about DNA have been overturned. Having overcome the arrogant assumption that what we don’t understand isn’t important, we have discovered a whole new world which we are just now beginning to explore.
So what did we learn from this little history lesson? Firstly, that science makes mistakes. BIG mistakes. Going from 3% useful DNA to over 30% useful DNA (and climbing) is a BIG mistake (a tenfold error). Secondly, that science can correct itself, and it can do so relatively quickly. Making a 180 like that in a matter of a decade is laudable. Not that this is a good thing overall. I mean that we should praise a science as we praise a child when he apologizes for hitting his sister. It is a shameful thing that happened, but better than if the apology never came.
And that is the story on Junk DNA. So let us continue our discussion by looking at what got us into this mess to begin with: a bad theory. The bad theory was that we arose by a sloppily process. We theorized that the mechanism by which we came about was a messy one with a lot of errors and inefficiencies. It has turned out that this, at least when it comes to DNA, was simply and clearly wrong.
May I humbly suggest another theory? I propose we think of the life as arising from an elegant process instead of a sloppy one. We ought to form a better theory, one that conforms to our data: that whatever formed life as we know it behaves as if it was an artist, an engineer and a designer.
When we see a genetic code, let’s not dismiss the 97% of the code as ‘junk’ when we don’t understand it. When we see a new protein, we ought to first assume it is part of an elegant system, not a useless piece of trash left over by an idiotic process. When we see an organ that we don’t understand, instead of first assuming a useless piece of flesh handed down by a process too stupid to take it out, let us be agnostic on its purpose and encourage ambitious scientists to try to figure it out. We have asserted our assumption when there is no data. We’ve pointed at the poor little organ and, for a century, shouted at it, “Useless!” I wouldn’t work under those conditions either.
It’s a good thing Duke researchers are leading the way by rejecting the old theory, or at least behaving like they did. Last year, they showed that the appendix has a useful role in repopulating good bacteria in the intestines and may be important in surviving intestinal diseases like Cholera (Hampton, T. A Use for the Appendix? JAMA. 2007; 298(21):2474).
You may think that all this talk about theories is simply an academic point, that we can agree to disagree, and that you can believe your way and I mine. But this is truly a life-and-death issue.
There was a huge reluctance to spend time or money studying non-coding DNA because of the assumption that it was junk. It turns out now that many diseases are actually caused by mutations in non-coding DNA. We can now do genetic counseling preventing transmission and are beginning to develop treatments. But this has only happened very recently because, until about a decade ago, we were still comfortable in our assumption that non-coding DNA was useless. The same goes for the appendix; 321,000 Americans were hospitalized in 2005 because of the appendix. How many lives may have been saved if we tried to figure out how the organ worked fifty years ago instead of dismissing it as another mistake by our sloppy friend evolution? How many people have died because of our stubbornness in clinging to a bad scientific theory?
Even if we were to assume atheistic evolution, I'm only suggesting that maybe we don't know who evolution really is, deep down. Maybe it is a process misunderstood. We may look at a man's desk and say he is sloppy and stupid, but that man may turn out to be a genius whose brilliance is hidden under a messy desk. Maybe, just maybe, evolution is that genius. We should, upon seeing the brilliance of evolution, reject the notion of it being stupid and embrace and even expect its genius.