Saturday, 24 July 2010

Genome not as useless as previously thought (was there any doubt?)

I had written earlier that only 4% of the human genome actually codes for proteins, relegating the rest to “junk DNA”. This is only partly true, at least according to a new study in Nature by Dr. Laura Poliseno et al, which suggests that approximately 40% plays a physical, regulatory role.

While many biologists tentatively accepted the 96%-junk-DNA figure, persuaded that the vast amount of parasitism at the organismal level could be mirrored at the DNA level, the concept has been quite unsettling. Poliseno’s hypothesis returns some sanity to our most fundamental unit of self.

According to Poliseno and team, plenty of the junkish pseudo-genes resemble other protein-coding genes, just enough that they attract and bind to floating bits of complimentary micro-RNA. The soup of complimentary DNA snippets would otherwise bind to the gene proper, and hinder the normal protein-producing machinery, thereby down-regulating the proper gene’s expression. He tested this idea using the PTEN tumour suppressor gene and its pseudogene PTENP1.

While knocking down one tenet, it does promote another—that gene expression is a complex, graded process, with nuances and interactions with the environment, that make any sort of one-to-one mapping of genome-to-phenotype, incredibly difficult.

However, this study does not entirely vindicate the genome as some well-ordered, perfectly designed recipe. 40% still leaves a lot of unexplained DNA. One of the more interesting bits are the LINE-1’s (which I wrote about in You are descended from Viruses) making up 20% of our genome, and seem to come from retroviruses, being good for nothing else but replicating and reinserting themselves in our genome.

Or are they? Dr. Gage noticed that LINE1s were more active in the brain tissue of developing mice than in other parts. He admits that they do not code for anything and really are just a random self-replicating nuisance. But could natural selection have taken advantage of such randomness as a beneficial process unto itself? Gage (GAYJuh) points out that developing brains a) have much more active LINE1s then other tissue, and b) they are over-resourced, with an initially superfluous number of neurons and connections which mostly deteriorate with age, leaving the core synapses for the more mature brain. Gage suggests that this deterioration is a sort of “survival of the fittest” of cells whose genes have been scrambled up by hyper-active LINE1s. Mostly, the random insertions of LINE1s will lead to neutral rearrangements, but sometimes they’ll disrupt another gene, and perhaps they may have a beneficial effect, and these he suggests are ones which survive to maturity.

Such a process occurs entirely in somatic cells, and is not passed on through gametes to the next generation. Rather, it is a sort of micro-natural selection that promotes an optimized network within a developing individual. Its an intriguing suggestion, and harkens suspiciously to the idea that complex networks themselves beget consciousness—an idea which is being explored more in computer science and problem solving, as in artificial neural networks.

Whether this study hypothesis bares out in the long run, it does suggest more scrutiny should be paid to the role of viruses in evolution and development. They are, after all, the most distilled essence of life possible.

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