Strands of Life. - Review - book review

Reason, August, 2000 by Ronald Bailey

Genome: The Autobiography of a Species in 23 Chapters, by Matt Ridley, New York: HarperCollins, 344 pages, $26.00

The race to find and map all human genes will likely end this year. This is years ahead of the original schedule set by the government-funded Human Genome Project, but stiff competition from the private sector, particularly from Celera Genomics, is now setting the pace of scientific discovery. Celera announced in April that it had completed the sequencing phase of an individual human being's genome and had now begun to assemble the genome segments into their proper order. In other words, Celera has completely read all of the 3.2 billion DNA base pairs that make up a person's genome.

The four DNA bases--adenine, thymine, cytosine, and guanine (ATCG)--combine into 64 three-letter genetic "words" called "codons" that specify a set of 20 amino acids and three "stop" signals. These amino acids, when linked together by reading the DNA that form the various genes, create the thousands of different proteins that make up the human body. These billions of DNA bases are located on 23 pairs of chromosomes which are harbored in nearly every human cell. Such genetic information is really packed into us: If all of the DNA in a single human cell were stretched out, it would reach six feet in length.

By the time you read this, both Celera and the Human Genome Project likely will have completed draft versions of the human genome. What's more, Celera is sequencing the genomes of six men and women of differing ethnic backgrounds to find single nucleotide polymorphisms (SNPs). The SNPs are single-letter variations in genes that differ among people and that determine, among other things, susceptibility to disease and the ability to combat illness. The British Wellcome Trust and various pharmaceutical companies are also searching for SNPs by funding an "SNP Consortium" that plans to identify at least 300,000, and perhaps as many as 1,000,000, of the most common SNPs in human populations.

The speed with which all this is happening is fantastic. Just consider what has happened in half a year. In the December issue of Nature, the Human Genome Project published the genetic sequence of the first human chromosome to be fully mapped, chromosome 22. Chromosome 22 contains 545 known genes and perhaps as many as 1,000 in total. Some 27 human maladies, including one involved with schizophrenia, are linked to changes in genes on chromosome 22.

In March, Celera, working with the Berkeley Drosophila Genome Project, published the complete genome of that most important genetic research animal, the fruit fly Drosophila melanogaster. (Because fruit flies have relatively large, easy-to-see chromosomes and multiply so quickly, scientists have long used them to track genetic processes.) Writing in Science, the researchers identified nearly 14,000 genes, making the fruit fly genome the largest so far sequenced. The fruit fly is also the first insect and the first organism with a central nervous system to be sequenced. (The genomes of several bacteria and the nematode worm C. elegans had been sequenced earlier.) In April, the Human Genome Project announced that it had assembled "working drafts" of human chromosomes 5, 16, and 19. Working drafts mean that 90 percent of the DNA in the three chromosomes have been "read" at least five times. Each reading--or, if you will, each spell-checking--increases the accuracy of the sequences; reading a sequence 10 times i s considered necessary for complete accuracy.

In the May Nature, the Human Genome Project published the complete sequence for the smallest human chromosome, chromosome 21. Chromosome 21 contains only 225 genes, but those genes are important: Inheriting three copies of the chromosome causes Down Syndrome, the most common form of mental retardation, affecting one out of every 700 live births.

Based on the gene frequencies found on chromosomes 21 and 22, some researchers now believe that the total number of genes that it takes to make a human being might be as few as 40,000, rather than the 70,000 to 140,000 predicted earlier. In fact, there is now a betting pool among genomic scientists as to exactly how many genes go into human beings. (The bets cost $1 per guess this year, $5 next year, and $20 in 2002.) The result will be officially announced in 2003, on the 50th anniversary of the publication of James Watson and Francis Crick's famous double-helix paper, which first described the structure of DNA.

Because so much exciting progress is being made in genomic research, one wants a sure guide to help one understand where the science is going. Fortunately, that guide is at hand: Matt Ridley's excellent Genome: The Autobiography of a Species in 23 Chapters. Ridley, a zoologist and former American editor for The Economist, is both a knowledgeable scientist and an easy-to-read writer. Each of his chapters tours one of our 23 chromosome pairs, the structures inside our cells' nuclei on which our genes are located. By focusing on a particular gene at a time, Ridley is able to illustrate how genes cause disease, direct the production of proteins, or influence intelligence.