Dark Genome

Cosmologists are very troubled by the fact that they can’t account for (depending on whom you ask) 90% to 99% of the mass and energy of the universe. The nature of this “Dark Matter” is the most pressing problem of their field. However, biologists don’t seem nearly as perturbed by the fact that the purpose of a similar fraction of the mammalian genome is completely unknown. They are so unconcerned that only a small fraction of the genome is in the genes that code for proteins that much of the non-coding region is simply called junk DNA.

It has always perplexed me why most of our DNA would be junk. I can’t believe that 90% of the DNA has no use whatsoever. It would seem much more likely that this so-called junk DNA is necessary for genetic regulation. After all, the main reason I am different from another person is not in the differences in the proteins I carry but in how and when they are expressed. Darwin himself recognized that much of the variation in nature must be due to regulation.

A very nice paper by Peter Andolfatto in the October 20 issue of Nature shows that in the fruit fly between 40% to 70% of the DNA nucleotides situated between genes are under selection pressure by evolution. He showed this in a very clever way. He analyzed the DNA of two species of DrosophilaD. melanogaster and D. simulans and looked at the level of polymorphism (differences within a species) and divergence (differences between species) in the genome. As a control he looked at synonymous sites (region in the coding region of DNA where a change in the nucleotide does not change the amino acid it codes for because of redundancies in the nucleotide triplet code).

Andolfatto found that the rate of mutation in non-coding regions is slightly lower than in synonymous sites indicating these sites have undergone negative selection pressure. Additionally, he found that the divergence rate in selected sites was increased relative to the polymorphism indicating that they also experience positive selection pressure. In other words, most mutations in these regions are deleterious and thus are selected against but every once in a while a nucleotide substitution confers some advantage and this is selected for. The bottom line is that these non-coding regions are crucial for the survival of the organism.

What these non-coding regions are for is unknown. The current dogma says that gene expression is controlled by sets of transcription factors that act on various promoter regions. According to Alex Kondrashov in the accompanying News and Views piece, current estimates of the fraction of functionally important segments of mammalian non-coding DNA is less than 15%. Although, an equivalent study still needs to be done in mammals, I’m betting that a significant portion of what is thought of as junk DNA is used for regulation and in a completely novel way.

One thought on “Dark Genome

  1. “PostGenes” are no “junk”.See the “JunkDNA Portal” at http://www.junkdna.comNow, there is even an International PostGenetics Society (see http://www.postgenetics.org) with the sole agenda of putting “non-coding DNA” (maiden name “junkDNA”) into its proper first priority.Reasons:1) Humans are different from the rest *not* in their genes (99.9% of the genes of homo sapiens and the chimp are identical, but there is a full 4% difference in their “PostGenes”.2) Millions and millions of people suffer/die *not* because they have anything wrong with their “genes”, but there are (in many cases) identified and well documented glitches in the “junk”.3) For (protein-based) Nanotechnology, it is absolutely crucial to find the engineering principles of how “postgenes” contribute to natural/artificial protein synthesis, since even in bacteria it is *not* true that the DNA is “devoid of junk”. Non-coding DNA is an essential component and no living organism has been shown without at least about 4% “junkDNA”.4) Genomics seemed to be stuck with “Genetics” over-focusing on the “genes”. Developing countries are leapfrogging in Genomics by directly plungin into the R&D of “junkDNA” (PostGenetics) – just like they skipped land-line telephones and went “cellular”. (The – presently – 15 Founders represent 11 countries on 4 continents…)Nascence of PostGenetics is perhaps the biggest “disruption” of the 21st Century.One of the specific mathematical (fractal geometrical) paradigm to explain the Genes and PostGenes Synthesis is FractoGene, see http://www.fractogene.comDr. Andras Pellionisz(408) 732-9319


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