Page 91

hemoglobin are the following. What is the evolutionary relationship between three related a, ß, and g hemoglobin genes? What is the evolutionary relationship between the hemoglobin molecules from various organisms? What do these sequences tell us about the evolutionary history of humans, chimpanzees, and gorillas? Each of these questions can be approached, if not always entirely solved, by sequence comparison.

Sequence comparison is of tremendous interest to molecular biologists because it is becoming easy to determine DNA and protein sequences, whereas it remains difficult to determine molecular structure or function by experimental means. Thus, functional and structural clues from sequence analysis can save years of work at the laboratory bench. An important early example illustrates the point. Some years ago, molecular biologists compared the protein sequence encoded by a cancer-causing gene (or oncogene) called v-sis to the available database of protein sequences. Remarkably, a computer search revealed that the sequence showed more than 90 percent identity to the sequence of a previously discovered gene encoding a growth-stimulating molecule, called platelet-derived growth factor (PDGF). Instantly, cancer researchers had a precise hypothesis about how this oncogene causes unregulated cell growth. Subsequent experiments confirmed the guess.

Nowadays, molecular biologists routinely carry out such computer searches against the current databases (which now contain both protein and DNA sequences) and are rewarded with striking and suggestive matches at a high frequency (perhaps 20 to 30 percent for a new gene). In some cases, the matches extend across the entire length of the protein. In other cases, there is a strong match across a restricted domain—examples include particular sequences at the catalytic site of enzymes that hydrolyze adenosinetriphosphate (ATP) or at the DNAbinding site of proteins that regulate the activity of genes. The frequency with which such strong matches are found is a tribute to the tremendously conservative nature of evolution: many of the basic building blocks of proteins and DNA have been reused in hundreds of different ways.

For the majority of new sequences, however, there is no striking match in the database. Although this may change with time (some molecular biologists believe that there are only a few thousand or a few tens of thousands of basic architectural motifs for proteins and that it is



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement