DNA variation at the Sod locus of Drosophila melanogaster: An unfolding story of natural selection

Patterns of variation at the Sod locus of Drosophila melanogaster suggest that the protein polymorphism at this locus has very recently arisen. In addition, it appears that a previously rare DNA variant has been recently and rapidly driven to intermediate frequency. From the size of the region (>20 kb) that has been swept along with this rare variant, and patterns of linkage disequilibrium in the region, it is inferred that strength of selection was large (s > 0.01) and that the sweep occurred more than 25,000 generations ago. In addition, there are striking similarities to patterns of variation observed at the Est6 and Est-P loci, which are located approximately 1,000 kb from Sod.

Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions

The evolution of novelty in tightly integrated biological systems, such as hormones and their receptors, seems to challenge the theory of natural selection: it has not been clear how a new function for any one part (such as a ligand) can be selected for unless the other members of the system (e.g., a receptor) are already present. Here I show—based on identification and phylogenetic analysis of steroid receptors in basal vertebrates and reconstruction of the sequences and functional attributes of ancestral proteins—that the first steroid receptor was an estrogen receptor, followed by a progesterone receptor. Genome mapping and phylogenetic analyses indicate that the full complement of mammalian steroid receptors evolved from these ancient receptors by two large-scale genome expansions, one before the advent of jawed vertebrates and one after. Specific regulation of physiological processes by androgens and corticoids are relatively recent innovations that emerged after these duplications. These findings support a model of ligand exploitation in which the terminal ligand in a biosynthetic pathway is the first for which a receptor evolves; selection for this hormone also selects for the synthesis of intermediates despite the absence of receptors, and duplicated receptors then evolve affinity for these substances. In this way, novel hormone-receptor pairs are created, and an integrated system of increasing complexity elaborated. This model suggests that ligands for some “orphan” receptors may be found among intermediates in the synthesis of ligands for phylogenetically related receptors.

A demographic approach to selection

The concepts of demography provide a means of combining the ecological approach to population growth with the genetical approach to natural selection. We have utilized the demographic theory of natural selection developed by Norton and Charlesworth to analyze life history schedules of births and deaths for populations of genotypes in Drosophila pseudoobscura. Our populations illustrate a stable genetic equilibrium, an unstable genetic equilibrium, and a case of no equilibrium. We have estimated population growth rates and Darwinian fitnesses of the genotypes and have explored the role of population growth in determining natural selection. The age-specific rates of births and deaths provide insights into components of selection. Both viability and fertility are important components in our populations.

Rapid decline of fitness in panmictic populations of Drosophila melanogaster maintained under relaxed natural selection

The parameters of the spontaneous deleterious mutation process remain poorly known, despite their importance. Here, we report the results of a mutation accumulation experiment performed on panmictic populations of Drosophila melanogaster without any genetic manipulations. Two experimental populations were kept for 30 generations under relaxed natural selection. Each generation, 100 pairs were formed randomly, and every fecund pair contributed a son and a daughter to the next generation. Comparison with two controls, one cryopreserved and the other kept as the experimental populations but with long generation time, showed that the number of surviving offspring per female declined by 0.2% and 2.0% per generation under benign and harsh, competitive conditions, respectively. Thus, the mutational pressure on fitness may be strong and depends critically on the conditions under which fitness is assayed.

A unified theory of carcinogenesis based on order–disorder transitions in DNA structure as studied in the human ovary and breast

Fourier transform-infrared/statistics models demonstrate that the malignant transformation of morphologically normal human ovarian and breast tissues involves the creation of a high degree of structural modification (disorder) in DNA, before restoration of order in distant metastases. Order–disorder transitions were revealed by methods including principal components analysis of infrared spectra in which DNA samples were represented by points in two-dimensional space. Differences between the geometric sizes of clusters of points and between their locations revealed the magnitude of the order–disorder transitions. Infrared spectra provided evidence for the types of structural changes involved. Normal ovarian DNAs formed a tight cluster comparable to that of normal human blood leukocytes. The DNAs of ovarian primary carcinomas, including those that had given rise to metastases, had a high degree of disorder, whereas the DNAs of distant metastases from ovarian carcinomas were relatively ordered. However, the spectra of the metastases were more diverse than those of normal ovarian DNAs in regions assigned to base vibrations, implying increased genetic changes. DNAs of normal female breasts were substantially disordered (e.g., compared with the human blood leukocytes) as were those of the primary carcinomas, whether or not they had metastasized. The DNAs of distant breast cancer metastases were relatively ordered. These findings evoke a unified theory of carcinogenesis in which the creation of disorder in the DNA structure is an obligatory process followed by the selection of ordered, mutated DNA forms that ultimately give rise to metastases.

Evolutionary theory predicts late-life mortality plateaus

Most demographic data indicate a roughly exponential increase in adult mortality with age, a phenomenon that has been explained in terms of a decline in the force of natural selection acting on age-specific mortality. Scattered demographic findings suggest the existence of a late-life mortality plateau in both humans and dipteran insects, seemingly at odds with both prior data and evolutionary theory. Extensions to the evolutionary theory of aging are developed which indicate that such late-life mortality plateaus are to be expected when enough late-life data are collected. This expanded theory predicts late-life mortality plateaus, with both antagonistic pleiotropy and mutation accumulation as driving population genetic mechanisms.

Relative effects of female fecundity and male mating success on fertility selection in Drosophila pseudoobscura.

The fertility component of natural selection acting on chromosomal inversions in two experimental populations of Drosophila pseudoobscura was subdivided into the effects of female fecundity and male mating success. The offspring of the three female genotypes could be distinguished by their mitochondrial DNA haplotypes, thus permitting a direct measurement of the relative fecundities of the female genotype. The effects of male mating success on inversion frequency were measured by comparing inversion frequencies in parents and their offspring. Selection by fertility caused significant changes in inversion frequency in both populations. In one population, the changes in inversion frequency due to female fecundity and to male mating success were comparable. In the other population, however, the changes in inversion frequency due to male mating success were considerably larger than those due to female fecundity. The difference between the two populations underscores the intrinsic variability of the fertility component of fitness.

Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning.

We used [3H]thymidine to document the birth of neurons and their recruitment into the hippocampal complex (HC) of juvenile (4.5 months old) and adult blackcapped chickadees (Parus atricapillus) living in their natural surroundings. Birds received a single dose of [3H]thymidine in August and were recaptured and killed 6 weeks later, in early October. All brains were stained with Cresyl violet, a Nissl stain. The boundaries of the HC were defined by reference to the ventricular wall, the brain surface, or differences in neuronal packing density. The HC of juveniles was as large as or larger than that of adults and packing density of HC neurons was 31% higher in juveniles than in adults. Almost all of the 3H-labeled HC neurons were found in a 350-m-wide layer of tissue adjacent to the lateral ventricle. Within this layer the fraction of 3H-labeled neurons was 50% higher in juveniles than in adults. We conclude that the HC of juvenile chickadees recruits more neurons and has more neurons than that of adults. We speculate that juveniles encounter greater environmental novelty than adults and that the greater number of HC neurons found in juveniles allows them to learn more than adults. At a more general level, we suggest that (i) long-term learning alters HC neurons irreversibly; (ii) sustained hippocampal learning requires the periodic replacement of HC neurons; (iii) memories coded by hippocampal neurons are transferred elsewhere before the neurons are replaced.

Strong natural selection causes microscale allozyme variation in a marine snail.

Natural selection is one of the most fundamental processes in biology. However, there is still a controversy over the importance of selection in microevolution of molecular traits. Despite the general lack of data most authors hold the view that selection on molecular characters may be important, but at lower rates than selection on most phenotypic traits. Here we present evidence that natural selection may contribute substantially to molecular variation on a scale of meters only. In populations of the marine snail Littorina saxatilis living on exposed rocky shores, steep microclines in allele frequencies between splash and surf zone groups are present in the enzyme aspartate aminotransferase (allozyme locus Aat; EC. 2.6.1.1). We followed one population over 7 years, including a period of strong natural perturbation. The surf zone part of the population dominated by the allele Aat100 was suddenly eliminated by a bloom of a toxin-producing microflagellate. Downshore migration of splash zone snails with predominantly Aat120 alleles resulted in a drastic increase in surf zone frequency of Aat120, from 0.4 to 0.8 over 2 years. Over the next four to six generations, however, the frequency of Aat120 returned to the original value. We estimated the coefficient of selection of Aat120 in the surf zone to be about 0.4. Earlier studies show similar or even sharper Aat clines in other countries. Thus, we conclude that microclinal selection is an important evolutionary force in this system.