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Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation (U) appears in theories of nucleotide divergence and polymorphism, the evolution of sex and recombination, and the evolutionary consequences of inbreeding. However, estimates of U based on changes in allozymes or DNA sequences and fitness traits are discordant. Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography. From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u among the three mutation-accumulation-line genotypes. By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila, we estimate that U is 1.2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction.

The mutation rate per genome for local affecting fitness is crucial in theories of the evolution of sex and recombination and of outbreeding mechanisms. Mutational variation in fitness may also be important in the evolution of mate choice in animals. No information is available on the rate at which spontaneous mutations with small effects on fitness arise, although viability (probability of survival to adulthood) has been studied in Drosophila melanogaster. These experiments involved the accumulation of spontaneous mutations in the virtual absence of natural selection, in a set of independently maintained lines with a common origin. The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation (U) and the average homozygous effect of a new mutation of minor effect(s). For the second chromosome of D. melanogaster, the value of U is at least 0.17 (ref. 7), and (1-h)s is less than 0.02, where hs is the average decline in fitness of heterozygotes. As the second chromosome is about 40% of the genome, these data indicate a mutation rate per haploid genome of at least 0.42 for viability. Here we present similar data on the effects of homozygous spontaneous mutations on a measure of fitness in D. melanogaster.

ESTIMATES of the rate of mutation to mildly deleterious alleles are fundamental to the testing of theories of the maintenance of sexual reproduction1 and recombination2,3. There are, however, few estimates of this parameter4,5. We suggest that data on inbreeding depression in highly self-fertilizing populations might provide such estimates. The effect of inbreeding in reducing genetic load and inbreeding depression is well known6,7, but little attention has been paid to the magnitude of these quantities in highly inbred natural populations. Modelling of mutational load shows that highly self-fertilizing populations should still have some genetic load and inbreeding depression8–10. In such populations, inbreeding depression is the converse of heterosis and its magnitude can be estimated from the increase in fitness-related characteristics in individuals produced by intercrossing different strains. Here we derive the inbreeding depression expected in completely inbred populations, and use it to estimate mutation rates per genome for some plant species.

Repetitive DNA sequences form a large portion of the genomes of eukaryotes. The 'selfish DNA' hypothesis proposes that they are maintained by their ability to replicate within the genome. The behaviour of repetitive sequences can result in mutations that cause genetic diseases, and confer significant fitness losses on the organism. Features of the organization of repetitive sequences in eukaryotic genomes, and their distribution in natural populations, reflect the evolutionary forces acting on selfish DNA.

Two attractive theories for the evolution of senescence are based on the principle that the force of natural selection decreases with age. The theories differ in the type of age-specific gene action that they assume. Antagonistic pleiotropy postulates that pleiotropic genes with positive effects early in life and negative effects of comparable magnitude late in life are favoured by selection, whereas genes with the reverse pattern of action are selected against. Mutation accumulation assumes that deleterious mutant alleles with age-specific effects will equilibrate at a lower frequency if their effects are expressed early rather than late in life. Explicit models demonstrate that both mechanisms can lead to the evolution of senescent life histories under reasonable conditions. Antagonistic pleiotropy has gained considerable empirical support, but the evidence in support of mutation accumulation is more sparse. Here we report that the genetic variability of mortality in male Drosophila melanogaster increases greatly at very late ages, as predicted by the mutation accumulation hypothesis. The rate of increase in mortality with age exhibits substantial genetic and environmental variability. This result provides a possible explanation for recent observations of non-increasing mortality rates in very old flies.

Richard Dawkins takes the gloves off, so to speak, in his new book The God Delusion. The demerits of religion are the subject of the book, not just a sidebar as in previous works. Dawkins' latest, and biographies of Francis Crick and Jane Goodall, feature in this week's book reviews special.

In a recent News and Views1, J. P. Stoye discussed the potential health risks associated with the spread of endogenous proviruses from pigs and primates through the use of their organs for transplantation into humans. Although the risks to patients and the public from horizontal transmission may be as manageable as he represents, we would like to comment on his reference to the presence of vertically transmitted proviruses in the genomes of all mammals as “mementos”.

Nature 359, 58-60 (1992) IT has come to our attention that an important stock used in this paper was probably contaminated during the experiments we reported. We accumulated spontaneous mutations in the virtual absence of natural selection on many copies of a single second chromosome of Drosophila melanogaster.

Life History Invariants: Some Explorations of Symmetry in Evolutionary Ecology . By Eric L. Charnov. Oxford University Press: 1993. Pp. 167. £25, $32.50 (hbk); £13.50, $16.95 (pbk)

Caste and Ecology in the Social Insects. By G. F. Oster and E. O. Wilson. Pp. 352. (Princeton University Press: Princeton, New Jersey, and Guildford, UK, 1979.) Hardback £12.50; paperback £4.70.

There has been extensive theoretical study of the evolution of self-fertilization in hermaphroditic or monoecious flowering plants because self-compatible species with high rates of self-fertilization are often derived from outcrossing ancestors1–4. Such studies have shown that a gene causing an increased rate of self-fertilization has an advantage because the mother transmits genes via both pollen and egg to selfed progeny5, and thereby evades the ‘cost of meiosis’6–8. Selfing also may be advantageous if the amount of pollen available to fertilize ovules by outcrossing is limited1,2,4,6. However, these advantages are offset, at least partially, if the fitness of selfed progeny is lower than that of outcrossed progeny, due to inbreeding depression1,2,6,7,9,10. Biogeographical evidence suggests that reduced pollinator activity may be sufficient to counteract this disadvantage and permit the evolution of selfing in populations in ecologically marginal areas1–4, but direct evidence is usually lacking. Here we show that the self-fertile homostyle variant of the primrose Primula vulgaris, which reaches high frequencies in certain populations11, experiences a fertility advantage, in terms of seeds per plant, as a result of its high rate of self-fertilization.

FISHER'S theory of the evolution of dominance is based on the fact that heterozygotes for rare deleterious alleles, maintained by recurrent mutation from the wild-type allele at the locus, greatly outnumber homozygotes in a random-mating population at equilibrium1. The fitness of a heterozygote carrying a mutant and the wild-type allele can be written as 1 − hs (1 ⩾ h ⩾ 0), compared with fitnesses of 1 and 1 − s for wild-type and mutant homozygotes respectively. Fisher postulated that mutant alleles were originally semidominant, so that h > 0. He explained the fact that most mutations are observed to be recessive or nearly recessive to wild type as the result of selection for modifier genes which increase the fitness of the heterozygotes alone. He pointed out that selection to improve the fitness of the mutant homozygotes is likely to be relatively ineffective because of their rarity compared with the heterozygotes, and also because the presence of the wild-type allele in heterozygotes renders them more amenable to selection towards the wild type. Using this theory, the level of dominance of the mutant alleles, h, is gradually reduced towards zero, while s remains constant. Wright2 criticised this because the heterozygotes for mutant alleles are so rare that the intensity of selection on a gene which modifies h is of the same order as the rate of mutation, u, to deleterious alleles at the locus undergoing dominance modification. He suggested that such a weak selection pressure is unlikely to overcome the effects of random genetic drift, or the selective consequences of pleiotropic effects of the dominance modifier. Later theoretical work3,4 has confirmed Wright's conclusion about the intensity of selection on dominance modifiers, so that many geneticists have come to doubt the validity of Fisher's theory3. The principle of dominance modification when applied to balanced polymorphisms (for example, Batesian mimicry5) is not, of course, subject to this objection and is generally accepted. Fisher1, however, believed that the recessivity of mutant genes demonstrated the ability of even a minute selection pressure to cause significant evolutionary change. The issue cannot be settled by purely theoretical considerations, and it is evident that some empirical evidence capable of providing a critical test is required. (Demonstrations that dominance can be modified by artificial selection6,7, although of great interest, are not relevant to the question of the efficacy of selection pressures as small as those postulated in Fisher's theory.) This paper points out recent experimental evidence on the heterozygous effects of mutations affecting viability in Drosophila8 that seems to be inconsistent with Fisher's theory, and also looks at two alternative theories proposed by Haldane9.