borhood of 1×10–6. Westergaard (1955) also stresses the possibility that the doubling dose may be low, in the neighborhood of 3–6r.

15.4Estimates of the number of genes in man.—The haploid gene number in Drosophila is commonly placed at 5,000 to 10,000 (cf. Muller, 1935). The existence of the relatively enormous salivary gland cell chromosomes in Drosophila, and the usual correspondence between a genetic locus and a visible “band” in these chromosomes, provides an unusual opportunity for gene number estimates in this species. No corresponding situation has been established in man or any other mammal. It is commonly argued that man, because of his greater physiological complexity, must have more genes than Drosophila. There exists only one piece of objective evidence in support of this argument. Spuhler (1948) has pointed out that the mean total length of the chromosomes in late prophase nuclei in man is some 8.5 times that of Drosophila. If one assumes that the spacing of the genes in the chromosomes is similar in the two species, this permits an estimate of the haploid gene number in man of between 42,000 and 85,000. Current treatments of the problem use estimates of the haploid gene number of from 100,000 (Evans, 1949) to 5,000 (Muller, 1950; Slatis, 1955). The data, then, permit competent students of the problem to make assumptions varying by a factor of 20.

15.5The “accumulation factor.”—The term “accumulation factor” is applied to the ratio of “recessive” genes already present in the population to those arising spontaneously each generation through mutation. Evans (1949), the first to make use of this factor in calculations, assumed, “somewhat arbitrarily,” a value of 50. No discussion of the basis for this estimate is given. With his assumptions concerning average mutation rate (1×10-5) and haploid gene number (1×105), the total mutation rate per zygote would be 2.0, and the average number of accumulated “recessive” genes per individual would be 100.

Muller (1950), on the other hand, after an extensive discussion of the evidence regarding the average degree of dominance of Drosophila genes, arrives at an “accumulation factor”— his p value—of 40, writing at the same time that there is “such a lamentable paucity of numerical values for human beings, or for any vertebrates, of a type which would throw light on the actual values of these factors, that we cannot feel too secure in regarding even 40 as a lower limit for p” (p. 141). The total mutation rate per gamete t), i.e., the product of gene number×average mutation rate, is set for purposes of calculation at 0.1. Introducing a factor of 2 to make allowance for the fact that selection probably operates predominantly on heterozygotes, the average number of “recessive” deleterious genes carried by a human being is placed at 2×0.1×40=8. In a later calculation, Muller (1954) adopts a figure of 0.3 as the total mutation rate, and suggests a figure of 100 for p. This leads to an estimate of 60 for the average number of recessive deleterious genes for which each individual is heterozygous.

Slatis (1954) has attempted a direct calculation of the frequency of abnormal autosomal recessive genes in man, from a consideration of the outcome of first cousin marriages. Data are presented on 17 sibships, in nine of which defects occur that are attributed to recessive inheritance. This leads to the estimate that “the average person is heterozygous for eight abnormal genes” (p. 418). Although the method is a valuable contribution, the data are unfortunately so biased as to be practically worthless for a calculation of this type. As Slatis points out, five of these nine families were ascertained because of the abnormality. Furthermore, two of the four remaining traits (polydactyly, distal webbing of the digits) are frequently due to dominant genes of irregular penetrance. If one discards those sibships, the data remaining are insufficient for a calculation of this type. The extensive data on the children born to consanguineous parents which were collected in the course of the present study, although still incompletely analyzed, are at marked variance with those of Slatis as regards frequency of appearance of genetic defect in the offspring.

In his later discussion of the results of the induction of mutations by irradiation, Slatis (1955) uses this figure of 8 for the average number of recessive deleterious genes present in man. Muller's above-quoted estimate of 60 is dismissed as “obviously too high,” on the basis of a calculation which assumes that each of these recessive genes has a clear-cut and readily demonstrable effect. While we hold no particular brief for either Evans' estimate of 50 nor Muller's of 60, Slatis' rejection of estimates of this magnitude appears to be based on the mis



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