Good for Us, Good for Them?

In the age of comparative biology, human beings will know their animal relatives—and themselves—like never before.

ALEX LASH

In coming decades, we�ll remember 2003 as a pivotal year in genetic science and in the way human beings think about their place in the natural world.

It is now three years since a draft of the human genome sequence was released to much fanfare. But the gene map was only completed this past year. And just as the final pieces of the human puzzle were falling into place, other genome projects were underway, such as the dog, the honeybee, and our closest living relative, the chimpanzee. By the time you read this, the chimp genome will have been sequenced and made public, adding to the more than 150 genomes now laid bare for scientific research.

The chimp genome is estimated to be 98% to 99% identical to our own. The slight differences should be quite revealing in many ways. Indeed, the genes we have and that chimps lack, and vice versa, could crack open several mysteries of what it means to be human: to think creatively, to walk upright, to adapt to practically every ecosystem on earth, and to read and write articles in science publications.

Far more urgently, the chimp genome may also help us solve a mystery of AIDS—how the human immunodeficiency virus (or at least the particular HIV strain that has claimed more than 20 million lives) jumped from chimpanzees to humans.

Before going further, it�s important to understand that a genome, even a complete one like the human genome, with its 3.2 billion base pairs of nucleotides, does no good unless we can interpret it. Imagine unearthing a vast tome of Egyptian hieroglyphics; they mean nothing until value is assigned to the characters and their arrangements. We are well on our way to giving the genome meaning: our several billion pairs of nucleotides—adenine, thymine, cytosine, and guanine—are strung together to form patterns, some of which we recognize as genes that carry instructions for proteins, the building blocks of life; some of which seem to have other functions, like signaling to the genes to start and stop making proteins. Some of the patterns seem to be nonfunctional legacies of our ancestors, and many others remain a mystery. We have the entire set of hieroglyphs, and we know what some of them mean when put together in certain ways. We even know that a small percentage of them actually contain direct instructions for daily life, while a larger subset have regulatory functions, like instructions on how to arrange and read the instructions.

“Having the whole genome creates a resource for asking more sophisticated questions,” says Kerstin Lindblad-Toh, codirector for sequence and analysis on the chimp genome project and a veteran of other genome projects. Before sequencing the genome, “many people did lots of great work, but they had to look at one gene by itself and work hard to get the sequence.”

So how can we say, before the full chimpanzee genome has been published, that it differs from ours by only 1% or 2%? (Likewise, how do we know that we differ 2% to 3% from the gorilla and 3% to 4% from the orangutan?)

One answer is that we don�t know for sure. Laying bare genome sequences has provided scientists with a few surprises. For example, the human gene count was estimated to be at over 100,000, but the actual number is about 30,000. And the mouse, whose genome was cracked in 2002, has roughly the same number of genes as man.

Yet our predictive powers are sophisticated. We can look at parts of a genome and make reasonable assumptions about the whole. And with each completed genome, our ability to draw conclusions from incomplete sequences grows more accurate. As Dr. Lindblad-Toh says, many people have done great work to make current genomic elucidation not only possible but “semipredictive.” (She says she doesn�t expect “all that much change” as the analysis of the chimp genome gets under way.)

Given the year�s developments, it figures that 2003 would produce a book detailing the previous two decades of genetic investigation. For any person interested in the influence of genetics on zoölogy, AIDS research, criminal forensics, endangered species conservation, and public environmental policy, Stephen O�Brien�s Tears of the Cheetah and Other Tales from the Genetic Frontier is highly recommended reading.

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