James F. Crow

Anecdotal, Historical and Critical Commentaries on Genetics

Gene mutation rates are higher in males than in females and increase with paternal age. In his Perspective, [Crow][1] explains unexpected results from a study of a congenital disease called Apert's syndrome in which the likelihood of a child developing the disease increases with the age of the father ([ Goriely et al .][2]). The results of the new work imply that rather than sperm having a higher mutation rate, the harmful mutation may be positively selected perhaps because it confers some benefit within the cellular environment of the testis. [1]: http://www.sciencemag.org/cgi/content/full/301/5633/606 [2]: http://www.sciencemag.org/cgi/content/short/301/5633/643

The germline mutation rate in human males, especially older males, is generally much higher than in females, mainly because in males there are many more germ-cell divisions. However, there are some exceptions and many variations. Base substitutions, insertion-deletions, repeat expansions and chromosomal changes each follow different rules. Evidence from evolutionary sequence data indicates that the overall rate of deleterious mutation may be high enough to have a large effect on human well-being. But there are ways in which the impact of deleterious mutations can be mitigated.

▪ Abstract In the first half-century of genetics, 1900 to 1953, the main techniques were breeding experiments and microscopy. Emphasis was on transmission genetics and cytogenetics, and during the half-century these became mature sciences. But the gene remained elusive. In 1953, thanks to Watson and Crick, the nature of the gene was no longer a mystery. In the second half of the century, the techniques became more chemical and computers played an indispensable role. The emphasis was then on gene action and, in the human, on increasingly accurate gene mapping and the soon-to-be-completed DNA sequence. During the first half-century, human genetics was very primitive, but by the end of the century it was comparable to that of the best-studied species. This trend will surely extend to the next century. The humanitarian possibilities of new techniques are enormous, but social judgments about their use and the problems of an increasingly crowded planet temper our optimism.

TOM Jukes accepted our invitation to write a Perspectives on the early history of molecular evolution, and in August 1999 he sent a rough beginning containing some now-forgotten early history. He planned an extensive revision and continuation, but on November 1 his death intervened. We have decided to publish his early draft, realizing that it was but a start toward the article that he had planned.