Wednesday, August 28, 2013

The Dark Matter of ENCODE.

Now for something a bit different.

I suppose the latest advances in molecular biology and genetics are not really subject of interest to the majority of the manosphere. But, for its more religious and traditionalist members, some of the recent findings of the ENCODE project look like they will have more than just scientific significance.

One of the curious paradoxes of modern genetics is that most of genome seems to be composed of of what appeared to be non-functional "junk" . Roughly, mainstream scientific wisdom has determined that about 4% of genetic material codes for the proteins that build up our body, the rest of the stuff.............well....... we don't know. Scientists, in attempting to work out what this DNA does have performed experiements where they have "knocked out" some of this junk DNA, with the  offspring animals not seeming to suffer any ill effects from the deletion, confirming the notion of junk DNA.  Molecular Darwinism too,  is Ok with the idea, since it the random nature of genetic mutations would imply that not all our DNA be functional. My understanding of the matter is that mathematical models of Darwinian evolution predict fifteen percent of DNA to be "functional" and the rest to be junk.

Indeed, our favorite mass-man/cognitive miser evolutionary theoretician Richard Dawkins loved junk DNA. He used its existence to bash away at those who supported some from of intelligent design. Thundering from the pulpit, in 2009 he said;
"It stretches even their creative ingenuity to make a convincing reason why an intelligent designer should have created a pseudogene -- a gene that does absolutely nothing and gives every appearance of being a superannuated version of a gene that used to do something -- unless he was deliberately setting out to fool us... 
Leaving pseudogenes aside, it is a remarkable fact that the greater part (95 percent in the case of humans) of the genome might as well not be there, for all the difference it makes."
Now, this idea of junk DNA has always struck me as odd. One thing that struck me in my undergraduate years in biology was the notion that there was still so much to learn about, especially with regard to genetics, and that any definitve pronouncements on the matter were likely to be rash. But medicine and science have a good tradition of confidently pronouncing on subjects they woefully ignorant in. In the old days, when doctors didn't know about the functioning of the spleen or thymus, they declared these organs vestigial and non-functional and removed them with abandon; it was only years later that they were discovered to be vital for the development of immunity and the protection against certain types of the disease. My studies left me with the impression, which I still hold to this day, that there is very little waste when it comes to molecular machinery and that the system is very efficient.

Some other people must have had this notion as well and they decided to go "poking around" this junk DNA. In 2007 the U.S. National Human Genome Project Research Institute started and investigation called ENCODE program. It involved over four hundred scientists and its findings, released late last year, are simply stunning. Roughly 80% of the junk is "functional". (The other 20% was "silent" most likely, in my opinion, due to technical limitations and in due time will eventually be found to be "functional"). It appears from the project that  there is very little "junk." and the "junk DNA is responsible for the regulation of our genes through through a variety of mechanisms. One of the major ones being the the production  non coding RNA, a class of molecules whose significance has only appreciated recently.

The findings have unleashed some uncharacteristically sarcastic and bitter responses from the Darwinian pit bulls, such as is not seen in the clinical and staid world of molecular genetics. But they have a point, and the point concerns the definition of "functionality".  The Darwinians assert that the only thing that the ENCODE project have discovered is biochemical activity in bits of the junk DNA and not actual biochemical function. What they are arguing is that the discovered activity is nothing more than "transcriptional noise" or random biochemical activity. What's really surprising is the vehemence with which they are making their claims. The ENCODE scientists concede that they haven't demonstrate "function" as yet but it's very likely that the activity is functional.

But the data is beginning to surge in.

Prader Willi Syndrome and some variants of autism have now been found to be due to defects in the production of long non coding RNA as have other illnesses. Long non coding RNA seems to determine our brain architecture and neurological functioning.  As well as our embryonic development. Several cancers have now been linked to abnormalities of ncRNA expression.

More importantly, what appears to be one of the most damning papers for the Darwinians has just been released. (You're at the cutting edge of science here!) It appears to strongly vindicate the researchers of ENCODE and the abstract deserves to be quoted in full:
Known protein coding gene exons compose less than 3% of the human genome. The remaining 97% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic RNAs are functional. Here we directly observed with a large set of RNA-seq data covering a wide array of human tissue types that the majority of the genome is indeed transcribed, corroborating recent observations by the ENCODE project. Furthermore, using de novo transcriptome assembly of this RNA-seq data, we found that intergenic regions encode far more long intergenic noncoding RNAs (lincRNAs) than previously described, helping to resolve the discrepancy between the vast amount of observed intergenic transcription and the limited number of previously known lincRNAs. In total, we identified tens of thousands of putative lincRNAs expressed at a minimum of one copy per cell, significantly expanding upon prior lincRNA annotation sets. These lincRNAs are specifically regulated and conserved rather than being the product of transcriptional noise [ED]. In addition, lincRNAs are strongly enriched for trait-associated SNPs suggesting a new mechanism by which intergenic trait-associated regions may function. These findings will enable the discovery and interrogation of novel intergenic functional elements.
Game. Set. Match.

The vehemence which the Darwinian Atheists have attacked the ENCODE project is more than just a matter of defending a competing hypothesis, rather, what perceptive players have recognised is that deep philosophical issues are at stake here. Make no mistake, this is a Galileo moment.

John Mattick, a world renowned Australian researcher at the forefront of non-coding RNA research replied to the critics of ENCODE:
There may also be another factor motivating the Graur et al. and related articles (van Bakel et al. 2010; Scanlan 2012), which is suggested by the sources and selection of quotations used at the beginning of the article, as well as in the use of the phrase “evolution-free gospel” in its title (Graur et al. 2013): the argument of a largely non-functional genome is invoked by some evolutionary theorists in the debate against the proposition of intelligent design of life on earth, particularly with respect to the origin of humanity. In essence, the argument posits that the presence of non-protein-coding or so-called ‘junk DNA’ that comprises >90% of the human genome is evidence for the accumulation of evolutionary debris by blind Darwinian evolution, and argues against intelligent design, as an intelligent designer would presumably not fill the human genetic instruction set with meaningless information (Dawkins 1986; Collins 2006). [Ed] This argument is threatened in the face of growing functional indices of noncoding regions of the genome, with the latter reciprocally used in support of the notion of intelligent design and to challenge the conception that natural selection accounts for the existence of complex organisms (Behe 2003; Wells 2011). 
In any case, that our understanding of the remarkably complex processes underlying the molecular evolution of life, including the likely evolution of evolvability (Mattick 2009c), is incomplete should not be surprising. With the emergence of transformative technologies, such as massively parallel sequencing, which provide tools to view the inner molecular workings of the genome that were inconceivable less than a decade ago, it is as important as ever that we as scientists remain open to observations that challenge even the most fundamental paradigms that exist within biology today [Ed]
Mattick is not a creationist, he believes that these new findings are compatible with the "broad tenants" of evolutionary theory, but he does recognise the current Darwinian evolutionary understandings are seriously flawed. Make no mistake, one of the foundations of modernism has been seriously undermined by the latest findings in molecular genetics.

And what of our friend Mr Dawkins, what's his take on the new findings with regard to junk DNA?
"I have noticed that there are some creationists who are jumping on [the ENCODE results] because they think that's awkward for Darwinism. Quite the contrary it's exactly what a Darwinist would hope for[ED: See above quote], to find usefulness in the living world....

Whereas we thought that only a minority of the genome was doing something, namely that minority which actually codes for protein, and now we find that actually the majority of it is doing something. What it's doing is calling into action the protein-coding genes. So you can think of the protein-coding genes as being sort of the toolbox of subroutines which is pretty much common to all mammals -- mice and men have the same number, roughly speaking, of protein-coding genes and that's always been a bit of a blow to self-esteem of humanity. But the point is that that was just the subroutines that are called into being; the program that's calling them into action is the rest [of the genome] which had previously been written off as junk."
Seriously, sometimes you've just got to stand back and let them hang themselves.

HT: Egnorance blog for the Dawkins quotes

Finally, this post is dedicated to Simon Grey who feels there may be a bit of defeatism in my recent writings. Rest assured. There's still some fight in the old bastard.

Bonus.  John Mattick on Vimeo