DNA at 60: Still Much to Learn

On the diamond jubilee of the double helix, we should admit that we don't fully understand how evolution works at the molecular level

By Philip Ball and Nature magazine

Image: Wikimedia Commons/Yikrazuul

This week's diamond jubilee of the discovery of DNA's molecular structure rightly celebrates how Francis Crick, James Watson and their collaborators launched the 'genomic age' by revealing how hereditary information is encoded in the double helix. Yet the conventional narrative ? in which their 1953 Nature paper led inexorably to the Human Genome Project and the dawn of personalized medicine ? is as misleading as the popular narrative of gene function itself, in which the DNA sequence is translated into proteins and ultimately into an organism's observable characteristics, or phenotype.

Sixty years on, the very definition of 'gene' is hotly debated. We do not know what most of our DNA does, nor how, or to what extent it governs traits. In other words, we do not fully understand how evolution works at the molecular level.

That sounds to me like an extraordinarily exciting state of affairs, comparable perhaps to the disruptive discovery in cosmology in 1998 that the expansion of the Universe is accelerating rather than decelerating, as astronomers had believed since the late 1920s. Yet, while specialists debate what the latest findings mean, the rhetoric of popular discussions of DNA, genomics and evolution remains largely unchanged, and the public continues to be fed assurances that DNA is as solipsistic a blueprint as ever.

The more complex picture now emerging raises difficult questions that this outsider knows he can barely discern. But I can tell that the usual tidy tale of how 'DNA makes RNA makes protein' is sanitized to the point of distortion. Instead of occasional, muted confessions from genomics boosters and popularizers of evolution that the story has turned out to be a little more complex, there should be a bolder admission ? indeed a celebration ? of the known unknowns.

DNA dispute
A student referring to textbook discussions of genetics and evolution could be forgiven for thinking that the 'central dogma' devised by Crick and others in the 1960s ? in which information flows in a linear, traceable fashion from DNA sequence to messenger RNA to protein, to manifest finally as phenotype ? remains the solid foundation of the genomic revolution. In fact, it is beginning to look more like a casualty of it.

Although it remains beyond serious doubt that Darwinian natural selection drives much, perhaps most, evolutionary change, it is often unclear at which phenotypic level selection operates, and particularly how it plays out at the molecular level.

Take the Encyclopedia of DNA Elements (ENCODE) project, a public research consortium launched by the US National Human Genome Research Institute in Bethesda, Maryland. Starting in 2003, ENCODE researchers set out to map which parts of human chromosomes are transcribed, how transcription is regulated and how the process is affected by the way the DNA is packaged in the cell nucleus. Last year, the group revealed that there is much more to genome function than is encompassed in the roughly 1% of our DNA that contains some 20,000 protein-coding genes ? challenging the old idea that much of the genome is junk. At least 80% of the genome is transcribed into RNA.

Some geneticists and evolutionary biologists say that all this extra transcription may simply be noise, irrelevant to function and evolution. But, drawing on the fact that regulatory roles have been pinned to some of the non-coding RNA transcripts discovered in pilot projects, the ENCODE team argues that at least some of this transcription could provide a reservoir of molecules with regulatory functions ? in other words, a pool of potentially 'useful' variation. ENCODE researchers even propose, to the consternation of some, that the transcript should be considered the basic unit of inheritance, with 'gene' denoting not a piece of DNA but a higher-order concept pertaining to all the transcripts that contribute to a given phenotypic trait.

Source: http://rss.sciam.com/click.phdo?i=22468e1a163e79ec52d768c51bb020a7

ozzie guillen ozzie guillen buster posey eric holder eric holder carole king crystal renn