Why deciphering DNA code is so challenging?

DNA methylation
Christoph Bock (Max Planck Institute for Informatics)
wikimedia

BBC Future Health November 2 2012 has a clearly written and highly educational article by Ed Young "Will we ever ... reveal all the secrets of life from DNA?"

The difficulty lies in the fact often forgotten by us laymen that the DNA code is not just long complex sequences of amino acids but the 3D SHAPE is of crucial importance. This is another ballgame altogether.

As our technologies and understanding advance, will we eventually be able to look at a pile of raw DNA sequence and glean all the workings of the organism it belongs to? Just as physicists can use the laws of mechanics to predict the motion of an object, can biologists use fundamental ideas in genetics and molecular biology to predict the traits and flaws of a body based solely on its genes? Could we pop a genome into a black box, and print out the image of a human? Or a fly? Or a mouse?

Not easily. In complex organisms, some traits can be traced back to specific genes. If, for instance, you’re looking at a specific variant of the MC1R gene, chances are you’ve got a mammal in front of you, and it has red hair. Indeed, people have predicted that some Neanderthals were red-heads for precisely this reason. “But beyond that, predicting [if something is] a mouse or a whale or a armadillo, we still wouldn’t do well,” says Kruglyak.

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Genes encode the instructions for assembling proteins, molecular machines that perform vital jobs in our cells. A protein is a long chain of amino acids, and we can predict that chain with perfect precision.

But the chain also folds, origami-like, into a complex three-dimensional shape, and the shape dictates everything that the protein does, from the chemical reactions it speeds up to the other molecules it sticks to.

Discerning those shapes is laborious work, involving growing pure crystals of the proteins, and bombarding them with X-rays. And despite having hundreds of these structures, even the most powerful computers struggle to accurately compute a protein’s shape from the DNA sequences that produce them. “I see that challenge as the stifling one,” says Palsson.
Read the entire article here