Evolution Encoded

New discoveries about the rules governing how genes encode proteins have revealed nature's sophisticated "programming" for protecting life from catastrophic errors while accelerating evolution

On April 14, 2003. scientists announced to the world that they had finished sequencing the human genome - logging the three billion pairs of DNA nucleotides that describe how to make a human being. But finding all the working genes amid the junk in the sequence remains a further challenge, as does gaining a better understanding of how and when genes are activated and how their instructions affect the behavior of the protein molecules they describe.So it isno wonder that Human Genome Project leaderFrancis S. Collins has called the groups accomplishment only "the end of the beginning".

Collins was also alluding to an event commemorated that same week: the beginning of the beginning. 50 years earlier, when James D. Watson and Francis H. Crick revealed the structure of the DNA molecule itself. That, too, was an exciting time. Scientists knew that the molecule they were finally able to visualize contained nothing else than the secret of life, which permitted organisms to store themselves as a set of blueprints and convert this stored information back into live metabolism. In subsequent years, attempts to figure out how this conversion took place captivated the scientific world. DNA's alphabet was known to consist of only four types of nucleotide.So the information encoded in the double helix had to be decoded according to some rules to tell cells which of 20 amino acids to string together to constitute the thousands of proteins that make up billions of life-forms. Indeed, the entire living world had to be perpetually engaged in frenetic decryption, as eggs hatched, seeds germinated, fungus spread and bacteria divided.

But so little was understood at the time about the cellular machinery translating DNA's message that attempts to crack this genetic code focused on the mathematics of the problem. Many early proposals proved wrong, a few spectacularly, although their sheer ingenuity and creativity still provide fascinating reading. In fact, when the actual code was finally deciphered during the 1960s, it nearly disappointed. Nature's version looked less elegant than several of the theorists' hypotheses.

Only in recent years have new discoveries about the code revealedjust how sophisticated a piece of programming it really is. Why nature chose these basic rules and why they have survived three billion or so years of natural selection have started to become clear. We can now show that the code's rulesmay actually speed evolution while protecting life from making disastrous errors in protein synthesis. Studying the code is also providing clues to solving some of those remaining challenges facing laboratories in the post-genome era. In going back to the very beginning to understand the rules of life's underlying code, we are discovering tools for future research.

When we speak of the "code" and"decoding", we are being quite literal. Genetic instructions are stored in DNA and RNA. both made of one type of biochemical molecule, nucleic acid. But organisms are mostly built from (and by) a vary different type of molecule, protein. So although a gene is traditionally defined as the sequence of nucleotides that describes asingle protein, the genetic sentence containing that description must first be translated from one system of symbols into an entirelv different kind of system, rather like converting from Morse code to English.

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