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10 May 2008

Genesis

We are close to figuring out what we are made of, or are we?
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Chaitali Bhattacharjee
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What makes a human a human? Why are we so different from all other animals? What is it that makes us tick? These are questions that intrigued the human mind always. However, the answer kept eluding us till a series of momentous discoveries led one to believe that the answer lay in the unique genetic composition that every organism had. Finally, an extremely ambitious project was undertaken — that of mapping the whole human genome (the entire hereditary information of a given organism encoded in its DNA). What that meant was that one would exactly know every bead that formed the DNA of a human being. The task was (technically) completed amid a lot of excitement in the year 2000.

Though the whole genome got mapped, the result turned out to be a lesson in humility rather than a moment of exultation. There were approximately 30,000 odd genes that were identified in humans, a number rather close to that of genes found in the roundworm, Caenorhabditis elegans. This appeared humiliating. We shared the such a large number of genes with some ‘lowly’ worms! And yet, we claim to be more evolved, more advanced. If we at all had to substantiate our claim, we desperately needed answers.

What was it that we had missed or overlooked? The answers that we got were far too less as compared to the 'great expectations'. One could still not answer questions that would solve some of the mystery that had baffled humanity forever. For example, one still could not answer questions as to how one gene got activated at a particular point of life and not at other times — a question crucial to the understanding of physiology and pathologies.

About 35 per cent of C. elegans genes are closely related to human genes. Should we say, "Spot the differences!"

So, the search for the answers continued. There appeared some light at the end of the tunnel when scientists looked at what they had so far chosen to ignore: huge stretches of DNA that served no apparent purpose. In fact, the coding region (region that codes for proteins) accounts for only three per cent of the entire genome. The popular theory that held till now was that the rest of the DNA (called junk DNA) was nothing but an evolutionary artefact — stretches of DNA that might have had some purpose to serve in the past, but have no purpose to serve now. The rather disappointing news about the number of genes that the human genome encodes, as had been just learnt, forced scientists to look once more at the genome, this time with a more open mind.

It does not make much sense prima facie. Why would a cell waste so much of energy trying to replicate — make a ‘faithful’ copy of — the whole genome? In fact, the cell apparently wastes even more energy meticulously making RNA using the DNA template (a process called transcription) after which it simply cuts and throws away parts that it does not need and stitches the rest of the pieces together to get a final copy of the functional RNA (called mRNA), which can now be used as a template to make proteins. Making huge stretches just to throw away? Why would a cell do that? No, there definitely is something that we were missing.

We just started solving those problems when we saw that some parts of the DNA that did not code for proteins were found to code for the RNA which played a regulatory role in many processes. This in itself was a revelation. One of the most important (rather hyped) molecule is DNA. It is known today that DNA is nothing but a series of coded messages that a cell reads and deciphers in order to tell a cell what it should exactly do. Enter the interlocutor, RNA, which translates this message for the cell so that proteins, the building blocks of a cell, can be made. That was what was known — that RNA is nothing more than a messenger molecule that acted as an interlocutor for the complex language of the DNA, resulting in the production of proteins.

Now, this seemingly innocuous molecule has in the recent past been found to do much more than just that. It dictates terms to the DNA, telling it whether it should go ahead and make the proteins, in what levels to make them and so on. This has suddenly changed our perceptions of how important a macromolecule it actually is. The whole scenario is becoming more and more interesting. The answers that have trickled in, still do not account for about 92 per cent of the DNA that a cell is forced to carry. More questions? Sure! And seemingly more answers.

We now know that the non-coding DNA is, after all, not a barren stretch that a cell is forced to carry from generation to generation as an obligation. We have not solved the riddle fully yet, but there are answers out there — teasers that can drive you nuts or make you ecstatic marvelling at them. After all, this is the puzzle of life and this curtain raiser boosts the hope of life scientists to bring forth answers that can change our perceptions for all times to come. We seem to be just a wee bit closer to understanding the puzzle of life… Or are we?

The writer is a post-doctoral fellow at the Institute of Genomics and Integrative Biology, New Delhi

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Surajit Dasgupta treats no individual, organisation or institution as a holy cow.