A STRUCTURED COALESCENT PROCESS FOR SEASONALLY FLUCTUATING POPULATIONS

Many short‐lived organisms pass through several generations during favorable growing seasons, separated by inhospitable periods during which only small hibernating or estivating refugia remain. This induces pronounced seasonal fluctuations in population size and metapopulation structure. The first generations in the growing season will be characterized by small, relatively isolated demes whereas the later generations will experience larger deme sizes with more extensive gene flow. Fluctuations of this sort can induce changes in the amount of genetic variation in early season samples compared to late season samples, a classical example being the observations of seasonal variation in allelism in New England Drosophila populations by P.T. Ives. In this article, we study the properties of a structured coalescent process under seasonal fluctuations using numerical analysis of exact state equations, analytical approximations that rely on a separation of timescales between intrademic versus interdemic processes, and individual‐based simulations. We show that although an increase in genetic variation during each favorable growing season is observed, it is not as pronounced as in the empirical observations. This suggests that some of the temporal patterns of variation seen by Ives may be due to selection against deleterious lethals rather than neutral processes.     

Distribution of Gene Frequency as a Test of the Theory of the Selective Neutrality of Polymorphisms

The variation in gene frequency among populations or between generations within a population is a result of breeding structure and selection. But breeding structure should affect all loci and alleles in the same way. If there is significant heterogeneity between loci in their apparent inbreeding coefficients F=s_p²/p(1-p), this heterogeneity may be taken as evidence for selection. We have given the statistical properties of F and shown how tests of heterogeneity can be made. Using data from human populations we have shown highly significant heterogeneity in F values for human polymorphic genes over the world, thus demonstrating that a significant fraction of human polymorphisms owe their current gene frequencies to the action of natural selection. We have also applied the method to temporal variation within a population for data on Dacus oleae and have found no significant evidence of selection.     

On Measures of Gametic Disequilibrium

Various measures have been proposed for characterizing the statistical association that arises between alleles at different loci. Hedrick has compared these measures with the standardized measure D' proposed by Lewontin on the grounds that this latter measure is independent of allele frequency. Although D' has the same range for all allelic frequencies, in fact, D' is not "independent" of allele frequency, and no measure with that general property is possible for the multilocus association problem. The insolubility of this problem arises from the ill-defined nature of general "association."     

Distinguishing the Forces Controlling Genetic Variation at the Xdh Locus in Drosophila Pseudoobscura

Fifty-eight isochromosomal lines sampled from two natural populations of Drosophila pseudoobscura in California and one from Bogota, Colombia, were examined using four-cutter restriction mapping. A 4.6-kb region of the xanthine dehydrogenase locus was probed and 66 of 135 restriction sites scored were polymorphic. This predicts that on average every 12th bp would be polymorphic in this region for the genes surveyed if polymorphism occurred randomly along the coding region. In addition, there were 12 insertion/deletion polymorphisms. Forty-nine distinct haplotypes were recognized in the 58 lines examined. The most common haplotype obtained a frequency of only 5%. Measures of base pair heterozygosity (0.0097) and linkage disequilibrium lead to a predicted population size in the range of 1.2-2.4 X 10(6) for the species. High levels of recombination (including gene conversion) can be inferred from the presence of all four gametic types in the data set.     

The Sensitivity of Gel Electrophoresis as a Detector of Genetic Variation

Three experiments based on an idea of YOUDERIAN have been performed to determine the proportions and kinds of amino acid substitutions that are detected by gel electrophoresis when applied to surveys of protein variation in populations. The experiments involved applying the sequential method of electrophoresis under several conditions of pH and gel concentration to a large sample of human hemoglobins with known amino acid substitutions. In the first experiment, a random sample of 20 different hemoglobin variants was studied, and these were separated into 17 distinct electrophoretic classes by three sequential gel conditions, thus giving a detectability of 85%. A single pass under standard conditions detected eight classes. The second experiment compared groups of substitutions that were chemically identical, but in different positions in the alpha and beta chains, while the third experiment compared pairs of substitutions that were charge equivalent, but chemically different at the same chain position. The sequential method distinguished 90% of all chemically identical substitutions when they were at different chain locations, and four out of five charge equivalent but chemically different substitutions at the same site. Examination of the location of each substitution in the three-dimensional structure of hemoglobins showed that interior substitutions usually are less different from Hb A than are surface substitutions and that local interactions with chain and spatial neighbors are sufficient to distinguish substitutions in very similar positions on the outside of the molecule. The "charge ladder" model of electrophoretic classes is clearly incorrect, and it appears that sequential gel electrophoresis as practiced in our Drosophila surveys has detected a substantial fraction of amino acid substitutions if hemoglobin is regarded as a model. This estimate may be modified as other molecules beside hemoglobin are subjected to similar calibration experiments.