Ethnohistory, genetics, and cancer mortality in Europeans

Geographic variation in cancer rates is thought to be the result of two major factors: environmental agents varying spatially and the attributes, genetic or cultural, of the populations inhabiting the areas studied. These attributes in turn result from the history of the populations in question. We had previously constructed an ethnohistorical database for Europe since 2200 B.C., permitting estimates of the ethnic composition of modern European populations. We were able to show that these estimates correlate with genetic distances. In this study, we wanted to see whether they also correlate with cancer rates. We employed two data sets of cancer mortalities from 42 types of cancer for the European Economic Community and for Central Europe. We subjected spatial differences in cancer mortalities, genetic, ethnohistorical, and geographic distances to matrix permutation tests to determine the magnitude and significance of their association. Our findings are that distances in cancer mortalities are correlated more with ethnohistorical distances than with genetic distances. Possibly the cancer rates may be affected by loci other than the genetic systems available to us, and/or by cultural factors mediated by the ethnohistorical differences. We find it remarkable that patterns of frequently ancient ethnic admixture are still reflected in modern cancer mortalities. Partial correlations with geography suggest that local environmental factors affect the mortalities as well.     

Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci

Using the generalized stepwise mutation model, we propose a method of estimating the relative mutation rates of microsatellite loci, grouped by the repeat motif. Applying ANOVA to the distributions of the allele sizes at microsatellite loci from a set of populations, grouped by repeat motif types, we estimated the effect of population size differences and mutation rate differences among loci. This provides an estimate of motif-type-specific mutation rates up to a multiplicative constant. Applications to four different sets of di-, tri-, and tetranucleotide loci from a number of human populations reveal that, on average, the non-disease-causing microsatellite loci have mutation rates inversely related to their motif sizes. The dinucleotides appear to have mutation rates 1.5–2 times higher than the tetranucleotides, and the non-disease-causing trinucleotides have mutation rates intermediate between the di- and tetranucleotides. In contrast, the disease-causing trinucleotides have mutation rates 3.9–6.9 times larger than the tetranucleotides. Comparison of these estimates with the direct observations of mutation rates at microsatellites indicates that the earlier suggestion of higher mutation rates of tetranucleotides in comparison with the dinucleotides may stem from a nonrandom sampling of tetranucleotide loci in direct mutation assays.     

Reduced inbreeding depression after species range expansion

Many species expanded their geographic ranges from core “refugium” populations when the global climate warmed after the Pleistocene. The bottlenecks that occur during such range expansions diminish genetic variation in marginal populations, rendering them less responsive to selection. Here, we show that range expansion also strongly depletes inbreeding depression. We compared inbreeding depression among 20 populations across the expanded range of a common European plant, and found that marginal populations had greatly reduced inbreeding depression. Similar patterns were also revealed by multilocus computer simulations. Low inbreeding depression is predicted to ease conditions for the evolution of self-fertilization, and selfing is known to be particularly frequent in marginal populations. Therefore, our findings expose a remarkable aspect of evolution at range margins, where a history of expansion can reverse the direction of selection on the mating system, providing a parsimonious explanation for the high incidence of selfing in marginal populations.     

Genetic Differentiation Within and Between Species of the Drosophila willistoni Group

We describe allelic variation at 28 loci in six Caribbean populations of four sympatric species of Drosophila. Within any one species the allelic frequencies are very similar from population to population, although there is evidence of local as well as regional genetic differentiation. The genetic distance is greater between populations from different islands than between populations of the same island. When the allelic frequencies are compared between different species, a remarkable pattern appears. In any pair of species nearly half of the loci have essentially identical allelic frequencies, while nearly the other half of the loci have different alleles and in different frequencies. The loci with nearly identical allelic frequencies are different when different pairs of species are compared. The patterns of allelic variation within and between species are inconsistent with the hypothesis that the variation is adaptively neutral. Migration or mutation cannot explain the patterns of genetic variation, either. Balancing natural selection is the main process maintaining protein polymorphisms in natural populations.     

Detecting immigration by using multilocus genotypes

Immigration is an important force shaping the social structure, evolution, and genetics of populations. A statistical method is presented that uses multilocus genotypes to identify individuals who are immigrants, or have recent immigrant ancestry. The method is appropriate for use with allozymes, microsatellites, or restriction fragment length polymorphisms (RFLPs) and assumes linkage equilibrium among loci. Potential applications include studies of dispersal among natural populations of animals and plants, human evolutionary studies, and typing zoo animals of unknown origin (for use in captive breeding programs). The method is illustrated by analyzing RFLP genotypes in samples of humans from Australian, Japanese, New Guinean, and Senegalese populations. The test has power to detect immigrant ancestors, for these data, up to two generations in the past even though the overall differentiation of allele frequencies among populations is low.     

Domestication of a Mesoamerican cultivated fruit tree, Spondias purpurea

Contemporary patterns of genetic variation in crops reflect historical processes associated with domestication, such as the geographic origin(s) of cultivated populations. Although significant progress has been made in identifying several global centers of domestication, few studies have addressed the issue of multiple origins of cultivated plant populations from different geographic regions within a domestication center. This study investigates the domestication history of jocote (Spondias purpurea), a Mesoamerican cultivated fruit tree. Sequences of the chloroplast spacer trnG-trnS were obtained for cultivated and wild S. purpurea trees, two sympatric taxa (Spondias mombin var. mombin and Spondias radlkoferi), and two outgroups (S. mombin var. globosa and Spondias testudinus). A phylogeographic approach was used and statistically significant associations of clades and geographical location were tested with a nested clade analysis. The sequences confirm that wild populations of S. purpurea are the likely progenitors of cultivated jocote trees. This study provides phylogeographic evidence of multiple domestications of this Mesoamerican cultivated fruit tree. Haplotypes detected in S. purpurea trees form two clusters, each of which includes alleles recovered in both cultivated and wild populations from distinct geographic regions. Cultivated S. purpurea populations have fewer unique trnG-trnS alleles than wild populations; however, five haplotypes were absent in the wild. The presence of unique alleles in cultivation may reflect contemporary extinction of the tropical dry forests of Mesoamerica. These data indicate that some agricultural habitats may be functioning as reservoirs of genetic variation in S. purpurea.     

Y chromosome diversity,human expansion,drift, and cultural evolution

The relative importance of the roles of adaptation and chance in determining genetic diversity and evolution has received attention in the last 50 years, but our understanding is still incomplete. All statements about the relative effects of evolutionary factors, especially drift, need confirmation by strong demographic observations, some of which are easier to obtain in a species like ours. Earlier quantitative studies on a variety of data have shown that the amount of genetic differentiation in living human populations indicates that the role of positive (or directional) selection is modest. We observe geographic peculiarities with some Y chromosome mutants, most probably due to a drift-related phenomenon called the surfing effect. We also compare the overall genetic diversity in Y chromosome DNA data with that of other chromosomes and their expectations under drift and natural selection, as well as the rate of fall of diversity within populations known as the serial founder effect during the recent “Out of Africa” expansion of modern humans to the whole world. All these observations are difficult to explain without accepting a major relative role for drift in the course of human expansions. The increasing role of human creativity and the fast diffusion of inventions seem to have favored cultural solutions for many of the problems encountered in the expansion. We suggest that cultural evolution has been subrogating biologic evolution in providing natural selection advantages and reducing our dependence on genetic mutations, especially in the last phase of transition from food collection to food production.     

Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism.

Restriction maps of 145 human mtDNAs representing samples from five geographic regions were used to construct multilocus genotypes for 28 genetic loci of the mitochondrial genome. Alleles were defined as distinct combinations of the presence or absence of polymorphic restriction sites within each locus. The 28 loci included 13 genes encoding proteins, 10 genes specifying tRNAs, 2 genes specifying rRNAs, and 3 noncoding regions consisting of the D loop, the light strand origin of replication, and the 5' noncoding sequence. In 35 comparisons of allele frequency distributions to expected distributions predicted by neutral mutation theory (assuming an infinite alleles model), the results revealed that most genetic diversity values (71%) fell within the range predicted by the neutral model; however, excesses in the frequencies of common alleles and in the number of singleton alleles within populations were observed at specific loci. Departures from the neutral mutation model are most readily explained by the effects of the recent expansion of the human population and the action of purifying selection. Coefficients of population differentiation suggest that gene flow of mtDNA types between certain geographic regions may be limited.     

Gene duplication in tetraploid fish: model for gene silencing at unlinked duplicated loci.

Several groups of fishes, including salmonids and catastomids, appear to have originated through genome duplication events. However, these two groups retain approximately 50% of the loci examined as functioning duplicates, despite the passage of 50 million years or more of mutation and selection. Although other effects are not excluded, this apparently slow rate of duplicate silencing can be explained in terms of the effects of selection against defective double homozygotes to unlinked duplicates. We have derived a computer simulation of genetic drift that affords direct evaluation of the effects of population size (N), mutation rate (micron), initial allele frequencies, back mutation, fitness, and time on the probability of fixation for null alleles at unlinked duplicate loci. The results show that this probability is approximately linearly related to population size for N greater than or equal to 10(3). Specifically, for naive populations, the time for 50% probability of gene silencing is approximately equal to 15N + micron-3/4 generations. The retention of 50% of the loci as functional duplicates may therefore result from the large effective size of salmonid and catastomid populations. The results also show that, under most conditions for populations of 2000--3000 or larger, unlinked duplicate loci will be sustained in the functional state longer than tandem (linked) duplicates and hence are available for evolution of new functions for a longer time.     

High amounts of genetic differentiation between populations of the malaria vector Anopheles arabiensis from West Africa and eastern outer islands.

Polymorphism at nine microsatellite loci was examined to assess the level of genetic differentiation between four Anopheles arabiensis populations from Senegal, the high plateau of Madagascar, and Reunion and Mauritius islands. Eight of nine loci showed great polymorphism (2-16 alleles/locus) and significant genetic differentiation was revealed between all four populations by F- and R-statistics, with Fst estimates ranging from 0.080 to 0.215 and equivalent Rst values ranging between 0.022 and 0.300. These high amounts of genetic differentiation are discussed in relation to geographic distance including large bodies of water, and history of mosquito settlement, and insecticide use on the islands. The results suggest that historical events of drift rather than mutation are probably the forces generating genetic divergence between these populations, with homogenization of the gene pool by migration being drastically restricted across the ocean.     

Global variation in the genetic and biochemical basis of diamondback moth resistance to Bacillus thuringiensis

Insecticidal proteins from the soil bacterium Bacillus thuringiensis (Bt) are becoming a cornerstone of ecologically sound pest management. However, if pests quickly adapt, the benefits of environmentally benign Bt toxins in sprays and genetically engineered crops will be short-lived. The diamondback moth (Plutella xylostella) is the first insect to evolve resistance to Bt in open-field populations. Here we report that populations from Hawaii and Pennsylvania share a genetic locus at which a recessive mutation associated with reduced toxin binding confers extremely high resistance to four Bt toxins. In contrast, resistance in a population from the Philippines shows multilocus control, a narrower spectrum, and for some Bt toxins, inheritance that is not recessive and not associated with reduced binding. The observed variation in the genetic and biochemical basis of resistance to Bt, which is unlike patterns documented for some synthetic insecticides, profoundly affects the choice of strategies for combating resistance.     

Genetics and the origin of bird species

External (environmental) factors affecting the speciation of birds are better known than the internal (genetic) factors. The opposite is true for several groups of invertebrates, Drosophila being the outstanding example. Ideas about the genetics of speciation in general trace back to Dobzhansky who worked with Drosophila. These ideas are an insufficient guide for reconstructing speciation in birds for two main reasons. First, speciation in birds proceeds with the evolution of behavioral barriers to interbreeding; postmating isolation usually evolves much later, perhaps after gene exchange has all but ceased. As a consequence of the slow evolution of postmating isolating factors the scope for reinforcement of premating isolation is small, whereas the opportunity for introgressive hybridization to influence the evolution of diverging species is large. Second, premating isolation may arise from nongenetic, cultural causes; isolation may be affected partly by song, a trait that is culturally inherited through an imprinting-like process in many, but not all, groups of birds. Thus the genetic basis to the origin of bird species is to be sought in the inheritance of adult traits that are subject to natural and sexual selection. Some of the factors involved in premating isolation (plumage, morphology, and behavior) are under single-gene control, most are under polygenic control. The genetic basis of the origin of postmating isolating factors affecting the early development of embryos (viability) and reproductive physiology (sterility) is almost completely unknown. Bird speciation is facilitated by small population size, involves few genetic changes, and occurs relatively rapidly.     

Preliminary data on the genetic differentiation of Onchocerca volvulus in Africa (Nematoda: Filarioidea)

Data are reported on the genetic structure of three Onchocerca volvulus populations, respectively from Mali (savanna), Ivory Coast (forest), and Zaire (forest gallery in savanna). Electrophoretic analysis, carried out on 25 gene-enzyme systems, has shown a remarkable genetic heterogeneity existing within O.volvulus. Zaire and West Africa populations appear chiefly differentiated at Mdh-1 and 6Pgdh loci, their average Nei's genetic distance being 0.11. In West Africa Nei's D found between the savanna and forest samples is 0.04. The savanna population from Zaire is more similar to the savanna one from Mali (D = 0.09) than to the forest one from Ivory Coast (D = 0.13). This appears mainly due to the loci Ldh and Hbdh (possibly linked), some alleles of which seem to be selected for in forest populations (Ldh110, Hbdh108), while others in the savanna ones (Ldh100, Hbdh100). The hypothesis that the discrepant epidemiological patterns of human onchocerciasis are related to intrinsic differences in the parasite seems supported by the obtained data. The differences in allele frequencies found at the reported loci appear strong enough to allow biochemical identification of O. volvulus populations from different geographic regions and different habitats.     

Evolution of codon usage bias in Drosophila

We first review what is known about patterns of codon usage bias in Drosophila and make the following points: (i) Drosophila genes are as biased or more biased than those in microorganisms. (ii) The level of bias of genes and even the particular pattern of codon bias can remain phylogenetically invariant for very long periods of evolution. (iii) However, some genes, even very tightly linked genes, can change very greatly in codon bias across species. (iv) Generally G and especially C are favored at synonymous sites in biased genes. (v) With the exception of aspartic acid, all amino acids contribute significantly and about equally to the codon usage bias of a gene. (vi) While most individual amino acids that can use G or C at synonymous sites display a preference for C, there are exceptions: valine and leucine, which prefer G. (vii) Finally, smaller genes tend to be more biased than longer genes. We then examine possible causes of these patterns and discount mutation bias on three bases: there is little evidence of regional mutation bias in Drosophila, mutation bias is likely toward A+T (the opposite of codon usage bias), and not all amino acids display the preference for the same nucleotide in the wobble position. Two lines of evidence support a selection hypothesis based on tRNA pools: highly biased genes tend to be highly and/or rapidly expressed, and the preferred codons in highly biased genes optimally bind the most abundant isoaccepting tRNAs. Finally, we examine the effect of bias on DNA evolution and confirm that genes with high codon usage bias have lower rates of synonymous substitution between species than do genes with low codon usage bias. Surprisingly, we find that genes with higher codon usage bias display higher levels of intraspecific synonymous polymorphism. This may be due to opposing effects of recombination.     

Genetic and morphological variations in populations of Oncomelania spp in China

Oncomelania snails are the intermediate hoste of Schistosoma japonicum in Asian countries. In order to understand the genetic and morphological variation of Oncomelania snails in mainland China, field snails from 31 localities were collected and investigated by means of allele enzyme electrophoresis and numerical taxonomical technics. Results demonstrated that out of 17 loci examined, seven polymorphic loci were presented. Genetic distance (Nei, 1978) among the populations varied from 0.03 to 0.27. The phenogenetic tree based on UPGMA cluster analysis showed that genetic diversity corresponded to geographic distribution along the Yangtze River, which provided supplementary genetic data about the evolution of Oncomelania spp. A morphological study showed that Mahalanobis' morphological distance ranged from 1.53 to 346.7. Both genetic and morphological data indicated that the diversity among populations of smooth shelled snails was higher than that among populations of ribbed shelled snails. A positive correlation (r = 0.80) between Mahalanobis' morphological distance and genetic distance supports the hypothesis that the different shell phenotypes represent different species or subspecies.     

Why hunter-gatherer populations do not show signs of Pleistocene demographic expansions

The mitochondrial DNA diversity of 62 human population samples was examined for potential signals of population expansions. Stepwise expansion times were estimated by taking into account heterogeneity of mutation rates among sites. Assuming an mtDNA divergence rate of 33% per million years, most populations show signals of Pleistocene expansions at around 70,000 years (70 KY) ago in Africa and Asia, 55 KY ago in America, and 40 KY ago in Europe and the Middle East, whereas the traces of the oldest expansions are found in East Africa (110 KY ago for the Turkana). The genetic diversity of two groups of populations (most Amerindian populations and present-day hunter-gatherers) cannot be explained by a simple stepwise expansion model. A multivariate analysis of the genetic distances among 61 populations reveals that populations that did not undergo demographic expansions show increased genetic distances from other populations, confirming that the demography of the populations strongly affects observed genetic affinities. The absence of traces of Pleistocene expansions in present-day hunter-gatherers seems best explained by the occurrence of recent bottlenecks in those populations, implying a difference between Pleistocene (approximately 1,800 KY to 10 KY ago) and Holocene (10 KY to present) hunter-gatherers demographies, a difference that occurred after, and probably in response to, the Neolithic expansions of the other populations.     

Dynamic patterns of adaptive radiation

Adaptive radiation is defined as the evolution of ecological and phenotypic diversity within a rapidly multiplying lineage. When it occurs, adaptive radiation typically follows the colonization of a new environment or the establishment of a "key innovation," which opens new ecological niches and/or new paths for evolution. Here, we take advantage of recent developments in speciation theory and modern computing power to build and explore a large-scale, stochastic, spatially explicit, individual-based model of adaptive radiation driven by adaptation to multidimensional ecological niches. We are able to model evolutionary dynamics of populations with hundreds of thousands of sexual diploid individuals over a time span of 100,000 generations assuming realistic mutation rates and allowing for genetic variation in a large number of both selected and neutral loci. Our results provide theoretical support and explanation for a number of empirical patterns including "area effect," "overshooting effect," and "least action effect," as well as for the idea of a "porous genome." Our findings suggest that the genetic architecture of traits involved in the most spectacular radiations might be rather simple. We show that a great majority of speciation events are concentrated early in the phylogeny. Our results emphasize the importance of ecological opportunity and genetic constraints in controlling the dynamics of adaptive radiation.     

Mutations arising in the wave front of an expanding population

The ability to infer the time and place of origin of a mutation can be very useful when reconstructing the evolutionary histories of populations and species. We use forward computer simulations of population growth, migration, and mutation in an analysis of an expanding population with a wave front that advances at a constant slow rate. A pronounced founder effect can be observed among mutations arising in this wave front where extreme population bottlenecks arise and are followed by major population growth. A fraction of mutations travel with the wave front and generate mutant populations that are on average much larger than those that remain stationary. Analysis of the diffusion of these mutants makes it possible to reconstruct migratory trajectories during population expansions, thus helping us better understand observed patterns in the evolution of species such as modern humans. Examination of some historical data supports our model.     

中国大陆钉螺种群遗传学研究——Ⅲ.遗传变异与地理分布的关系

本研究目的是通过检测中国大陆钉螺不同种群的等位基因频率,研究种群遗传变异与相应地理分布之关系,以确定流行区现场钉螺的种群结构。结果显示,7个多态基因位点的等位基因频率地理分布呈现3种类型:均衡、分散和非连续变向分布。3个主要多态基因位点(Est—4、Got和Mdh—2)均显示了非连续变向。样本种群间遗传距离与地理距离的回归分析表明,Logistic S曲线回归为最佳拟合曲线。结合其它数据,认为分裂亚群模型是中国大陆钉螺种群的基因结构模型。     

Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans

Theory concerning the evolution of sex and recombination and mutation load relies on information on rates and distributions of effects of deleterious mutations. Direct information on the genomic mutation rate in Drosophila implies that an accumulation of mildly deleterious mutations reduces viability of populations by at least 1% per generation. We carried out an experiment to measure the deleterious mutation rate in Caenorhabditis elegans, in which independent sublines were maintained with one hermaphrodite parent per generation, conditions that minimize the opportunity for natural selection and lead to random fixation of deleterious mutations. After 60 generations of mutation accumulation, negligible changes in mean reproductive output and lifespan occurred, but the genetic variance increased at rates typical for life history traits in other species. The estimated deleterious mutation rate per haploid genome for fitness, U, was 0.0026, a figure two orders of magnitude smaller than previously measured for viability in Drosophila.