Last month Rob Crowther wrote about a news article in Nature that opposed junk-DNA thinking. According to a new Nature News story, “The code within the code: Computational biologists grapple with RNA’s complexity,” scientists are just beginning to understand the complexity of the processes that create proteins in our cells. The article reports that the distinction we normally see in human technology between hardware and software breaks down in biology, where molecules like RNA can both carry messages and help process those messages — a “second genetic code,” or the “splicing code”:
One of the most beautiful aspects of the genetic code is its simplicity: three letters of DNA combine in 64 different ways, easily spelled out in a handy table, to encode the 20 standard amino acids that combine to form a protein.
But between DNA and proteins comes RNA, and an expanding realm of complexity. RNA is a shape-shifter, sometimes carrying genetic messages and sometimes regulating them, adopting a multitude of structures that can affect its function. In a paper published in this issue (see page 53), a team of researchers led by Benjamin Blencowe and Brendan Frey of the University of Toronto in Ontario, Canada, reports the first attempt to define a second genetic code: one that predicts how segments of messenger RNA transcribed from a given gene can be mixed and matched to yield multiple products in different tissues, a process called alternative splicing. This time there is no simple table — in its place are algorithms that combine more than 200 different features of DNA with predictions of RNA structure.
The article further explains that many small RNAs may regulate gene expression:
Much of the enthusiasm for understanding RNA is motivated by the discovery of small RNAs that do not code for protein, yet can regulate gene expression. The hunt is on to catalogue these RNAs and their targets — a quest aided by advances in algorithm design and the accumulation of genome sequences. This allows researchers to search the vast stretches of noncoding DNA between genes: the conservation of sections in many species could suggest that they have important functions.
Rebutting those who claim that much of our genome is useless, the article reports that “95% of the human genome is alternatively spliced, and that changes in this process accompany many diseases.” The actual research paper reports that much of this activity helps determine cell and tissue types, and the complexity of this “splicing code” is mind-boggling:
Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.
(Yoseph Barash, John A. Calarco, Weijun Gao, Qun Pan, Xinchen Wang, Ofer Shai, Benjamin J. Blencowe, & Brendan J. Frey, “Deciphering the splicing code,” Nature, Vol. 465:53-59 (May 6, 2010).)
A summary of this article also titled “Breaking the Second Genetic Code” in the print edition of Nature summarized this research thusly: “At face value, it all sounds simple: DNA makes RNA, which then makes protein. But the reality is much more complex. … The code is likely to work in a cell-autonomous manner and, consequently, may need to account for more than 200 cell types in mammals.” So what we’re finding in biology are:
- “beautiful” genetic codes that use a biochemical language;
- Deeper layers of codes within codes showing an “expanding realm of complexity”;
- Information processing systems that are far more complex than previously thought (and we already knew they were complex), including “the appearance of features deeper into introns than previously appreciated”
While Nature‘s articles on the splicing code are reporting evidence of protein-generating functions in our cells that require complex computer algorithms just to understand, what’s incredible is that a Nature piece published just two days earlier was titled “What a shoddy piece of work is man.” You read that right. Amazingly, it used purported deficiencies in the same protein-generating processes to argue against intelligent design (ID):
The ubiquity of introns — sequences that must be expensively excised from transcribed genes before translation to proteins — seems to be a potentially harmful encumbrance. And numerous regulatory mechanisms are needed to patch up problems in gene activity; for example, by silencing or destroying imperfectly transcribed mRNA — the template for protein synthesis. Regulatory breakdowns may cause disease.
Apparently forgetting that Scientific American argued that “[t]he failure to recognize the importance of introns ‘may well go down as one of the biggest mistakes in the history of molecular biology'” and that the paper by Baresh et al. furthered this trend by finding “features deeper into introns than previously appreciated,” the “What a shoddy piece of work is man” editorial goes on to argue that “botches are … precisely what we would expect from Darwinian evolution,” and asks, “Why design a genome so poorly that it needs all this surveillance?”
As an attorney who studied product liability law in law school, I’ve always been amazed by the fallacies in such spectacularly shallow critiques of ID. Tort law recognizes various classes of product defects that can render manufacturers liable. One class is the design defect, where the design itself is fundamentally flawed. Another is a manufacturing defect — where the standard design might work perfectly fine but occasionally a unit rolls off the production line with a mistake.
While manufacturers are typically held strictly liable in either situation, obviously the former case — a fundamental, ubiquitous design flaw — will wreak far more havoc on consumers than the latter case — the occasional manufacturing mistake. Yet the “breakdowns” that “cause disease” cited by Nature are akin to the latter, less severe type of manufacturer’s error, where the design might be fundamentally optimal but sometimes things break.
To argue that such breakdowns or disease refute ID is no better than citing the age-old theological objection regarding the problem of evil. In fact, this is exactly what Nature admits it’s doing, quoting a scientist contending that design flaws “extend the age-old theodicy challenge, traditionally motivated by obvious imperfections at the levels of human morphology and behavior, into the innermost molecular sanctum of our physical being.” But this argument has zero impact upon scientific arguments for ID (nor does it refute traditional theistic views of God unless you turn a blind eye to millennia of theological solutions to this problem). Does the presence of manufacturing defects necessarily mean that there is no intelligently designer — the manufacturer — behind the process? Of course not.
And when manufacturers use error-checking mechanisms — like what Nature disparages as undesigned “surveillance” mechanisms in the cell — aren’t those quality-control procedures also intelligently designed? How does the existence of a quality-control mechanism refute design? It’s hard to see how the existence of a quality control mechanism refutes design when all such mechanisms are, themselves, products of design.
The lesson here is that Nature is much more deliberately careful when expounding the complex details of biochemistry than it is when dealing with ID. One day Nature claims that error-checking mechanisms in the protein-creation process entail unnecessary “surveillance” that refutes ID. Two days later, it’s marveling at the “beautiful aspects of the genetic code” and the “expanding realm of complexity” we’re uncovering as we learn more about the inner workings of the processes that generate proteins.
The bottom line is that the more we learn about biology, the more we’re finding evidence of mass amounts of hidden functions for DNA and RNA. We’re also discovering a dramatic increase in the known complexity of the processes that create proteins, tissues, and cell-types. While Nature is eager to use fallacious arguments that attack ID (what they call with great bias, “the pseudo-scientific face of religious creationism”) it’s missing the huge evidence for ID that’s starting it in the face.
Nonetheless, if admitting your problem is the first step towards getting over it, then there’s a glimmer of hope. The article, “What a shoddy piece of work is man,” states:
However — although heaven forbid that this should seem to let ID off the hook — it is worth pointing out that some of the genomic inefficiencies Avise lists are still imperfectly understood. We should be cautious about writing them off as ‘flaws’, lest we make the same mistake evident in the labelling as ‘junk DNA’ genomic material that seems increasingly to play a biological role. There seems little prospect that the genome will ever emerge as a paragon of good engineering, but we shouldn’t too quickly derogate that which we do not yet understand.
By acknowledging that it was a mistake to “labe[l] as ‘junk DNA’ genomic material that seems increasingly to play a biological role,” Nature is beginning to see that a Darwinian mindset which apparently denigrates the complexity of biology is known to lead science down the wrong path.
One thing is clear: Nature shouldn’t expect its readers to take seriously editorial assertions like “[t]here seems little prospect that the genome will ever emerge as a paragon of good engineering” when two days later it publishes a second article reporting a “code within the code” of our DNA.
With such willfully blind and biased treatments of ID coming from the world’s most prestigious scientific journal, no wonder journals like BIO-Complexity are necessary to give ID the chance for a fair hearing. Heaven forbid we should let Nature off the hook for refusing to take ID the least bit seriously.