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Seek Function in Genomic Dark Matter, and Ye Shall Find

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The Department of Energy is very interested in finding new sources of fuel. Thinking that bacteria in cow's stomachs probably know some secrets to extracting energy from plant mass, they sent some biologists from Washington and California on a quest: look into the unknown genes of those microbes, and find ones that know how to break down cellulose.

The biologists went to work, focusing on the genes with unknown functions. Their paper in Biotechnology & Bioengineering describes their strategy for identifying "novel biomass-degrading enzymes from genomic dark matter."

Although recent nucleotide sequencing technologies have significantly enhanced our understanding of microbial genomes, the function of ?35% of genes identified in a genome currently remains unknown. To improve the understanding of microbial genomes and consequently of microbial processes it will be crucial to assign a function to this "genomic dark matter." Due to the urgent need for additional carbohydrate-active enzymes for improved production of transportation fuels from lignocellulosic biomass, we screened the genomes of more than 5,500 microorganisms for hypothetical proteins that are located in the proximity of already known cellulases. We identified, synthesized and expressed a total of 17 putative cellulase genes with insufficient sequence similarity to currently known cellulases to be identified as such using traditional sequence annotation techniques that rely on significant sequence similarity. The recombinant proteins of the newly identified putative cellulases were subjected to enzymatic activity assays to verify their hydrolytic activity towards cellulose and lignocellulosic biomass. Eleven (65%) of the tested enzymes had significant activity towards at least one of the substrates. This high success rate highlights that a gene-context based approach can be used to assign function to genes that are otherwise categorized as "genomic dark matter" and to identify biomass-degrading enzymes that have little sequence similarity to already known cellulases. (Emphasis added.)

They used a smart method, in other words, to cut to the chase: if an unknown gene sits near a gene with a known function, it probably has a similar function. Surprisingly, a high percentage did. Of unknown genes in proximity to cellulase enzymes (those that can act on cellulose), 65% showed functional activity in the presence of the cellulose. This doesn't mean that the other 6 genes (35%) did not have a function -- those functions remain to be discovered -- but by assuming function was there, they shed more light on "genomic dark matter."

The Department of Energy's Joint Genome Institute says there's a lot of room for future discoveries. "As much as a third of the genes identified in most genomes currently remain unknown, hindered in part by the inability of existing algorithms to assign functions to these genes and proteins." The fault, then, is not with the genes, but with previous strategies for finding out what they do. "This approach may also have utility in exploring genomic dark matter for additional enzymes of relevance to DOE interests in bioenergy and the environment."

Is This a Case of ID?

The researchers apparently made no use of evolutionary theory to make their discoveries. "Intelligent design" was not mentioned, either, but it is implicit: clearly, these scientists went looking for function in these unknown genes. That was the stated purpose: "exploring genomic dark matter for additional enzymes" -- proteins that do useful work. They figured that "hypothetical proteins" generated from these genes might have functions. Many of them did.

There's more evidence this is design-based research. The genes, in themselves, have no activity on cellulose: they are just sequences of DNA bases. Their function is to store information. It's only when the genes are transcribed and translated by molecular machines (each functional individually) that the function of the protein product (the ability to break down cellulose) can be assessed. It's function all the way down.

This story provides further evidence that design-based science is testable, productive, and useful: testable, because assuming design, these scientists predicted that function would be found, and tested that prediction; productive, because having found function in "genomic dark matter," they not only increased our understanding of biology, but constructed a method for finding more function; and useful, because the function they found leads to applications that can improve our lives by increasing the efficiency of biofuel generation.

We have no idea what these particular researchers believe, but you don't have to advocate intelligent design to do design-based science. Arguably that's how most science is done anyway.

Photo credit: Dieter van Baarle/Flickr.