Intraspecific variability in fractional composition of the serum proteins of the sturgeon Acipenser stellatus]

Comparative studies on fractional composition of the blood serum proteins in two sympatric populations of the sturgeon A. stellatus (South-Caspian and North-Caspian) have been made by means of polyacrylamide gel disc-electrophoresis. Serum proteins are fractionated into 13-18 electrophoretic components, the heterogeneity of proteins being somewhat higher in the North-Caspian population than in the South-Caspian one. Most pronounced differences were found in the relative content of albumins and beta-globulins. Special interest is attracted to different heterogeneity of albumins and beta-globulins (transferrins) in the two populations of the Caspian sturgeon.     

Estimation of past demographic parameters from the distribution of pairwise differences when the mutation rates vary among sites: application to human mitochondrial DNA.

Distributions of pairwise differences often called "mismatch distributions" have been extensively used to estimate the demographic parameters of past population expansions. However, these estimations relied on the assumption that all mutations occurring in the ancestry of a pair of genes lead to observable differences (the infinite-sites model). This mutation model may not be very realistic, especially in the case of the control region of mitochondrial DNA, where this methodology has been mostly applied. In this article, we show how to infer past demographic parameters by explicitly taking into account a finite-sites model with heterogeneity of mutation rates. We also propose an alternative way to derive confidence intervals around the estimated parameters, based on a bootstrap approach. By checking the validity of these confidence intervals by simulations, we find that only those associated with the timing of the expansion are approximately correctly estimated, while those around the population sizes are overly large. We also propose a test of the validity of the estimated demographic expansion scenario, whose proper behavior is verified by simulation. We illustrate our method with human mitochondrial DNA, where estimates of expansion times are found to be 10-20% larger when taking into account heterogeneity of mutation rates than under the infinite-sites model.     

Population differences of aspartate aminotransferase and peptidase in the bay mussel Mytilus edulis.

This investigation has demonstrated considerable heterogeneity among populations and some heterogeneity within populations in the distribution of alleles at two variant loci of Mytilus edulis. Although the causes of this variation remain obscure, some speculations have been made on the basis of available data. A cline for aspartate aminotransferase (AAT) alleles has been observed on the Pacific Coast. An immigration model has been proposed to explain the atypical ecological and genetic characteristics of large mussels found on Amchitka Island, Alaska. Marked differences were found in the distribution of peptidase alleles among collections from Southern California, the North Pacific Ocean, and New Jersey. Deviations from random distribution of phenotypes observed in comparisons made between large and small mussels from the New Jersey collection may reflect selection operating on these loci in this population.     

The stability of the G‐matrix: The role of spatial heterogeneity

The temporal stability of the genetic variance‐covariance matrix ( G ) has been discussed for a long time in the evolutionary literature. A common assumption in all studies, including empirical ones, is that spatial heterogeneity is minor such that the population can be represented by a single mean and variance. We use the well‐established allocation‐acquisition model to analyze the effect of relaxing of this assumption, simulating a case where the population is divided into patches with a variance in quality between patches. This variance can in turn differ between years. We found that changes in spatial variance in patch quality over years can make the G ‐matrix vary substantially over years and that the estimated genetic correlations, evolvability, and response to selection are different dependent on whether spatial heterogeneity is taken into account or not. This will have profound implications for our ability to predict evolutionary change and understanding of the evolutionary process.     

A mathematical and computational approach for integrating the major sources of cell population heterogeneity

Several approaches have been used in the past to model heterogeneity in bacterial cell populations, with each approach focusing on different source(s) of heterogeneity. However, a holistic approach that integrates all the major sources into a comprehensive framework applicable to cell populations is still lacking.In this work we present the mathematical formulation of a cell population master equation (CPME) that describes cell population dynamics and takes into account the major sources of heterogeneity, namely stochasticity in reaction, DNA-duplication, and division, as well as the random partitioning of species contents into the two daughter cells. The formulation also takes into account cell growth and respects the discrete nature of the molecular contents and cell numbers. We further develop a Monte Carlo algorithm for the simulation of the stochastic processes considered here. To benchmark our new framework, we first use it to quantify the effect of each source of heterogeneity on the intrinsic and the extrinsic phenotypic variability for the well-known two-promoter system used experimentally by Elowitz et al. (2002). We finally apply our framework to a more complicated system and demonstrate how the interplay between noisy gene expression and growth inhibition due to protein accumulation at the single cell level can result in complex behavior at the cell population level.The generality of our framework makes it suitable for studying a vast array of artificial and natural genetic networks. Using our Monte Carlo algorithm, cell population distributions can be predicted for the genetic architecture of interest, thereby quantifying the effect of stochasticity in intracellular reactions or the variability in the rate of physiological processes such as growth and division. Such in silico experiments can give insight into the behavior of cell populations and reveal the major sources contributing to cell population heterogeneity.     

Genetic Heterogeneity in Algerian Human Populations

The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region.     

HLA antigens and clinical subgroups of schizophrenia

Frequencies of HLA A, B, C, and DR antigens were studied in 100 schizophrenic patients and 919 controls from South Sweden. The patients were diagnosed according to the DSM III criteria and divided into four clinical subgroups (hebephrenic, paranoid, residual, and undifferentiated). In the schizophrenic patients as a whole significant increases were found for A2, A3, B17, B27, and Cw2 and decreases for A1, A11, and B8. A previous positive association with A9 from the same population was not confirmed. A significant heterogeneity between the four clinical subgroups was found for A3 and Bw35. Most of the associations between HLA antigens and schizophrenia reported in the literature appear to be fortuitous and dependent on the large number of trials made. However, confirmed increases have been found for A9 and B17, and confirmed decreases have been observed for A1 and B7. Some evidence for a heterogeneity between clinical subgroups was found in the present as well as in previous investigations.     

Evaluation of heterogeneity of DNA ploidy in early gastric cancers.

DNA ploidy has been shown to be a predictive parameter for prognosis in various solid tumours. The prognostic value of DNA-ploidy in gastric cancers is still a matter of controversy. A possible explanation for the discrepant results reported in the literature could be sampling error in tumours with multiple stemlines differing in DNA-ploidy. In order to determine whether or not such heterogeneity exists in early gastric carcinoma, we have performed DNA cytophotometry on multiple samples of a group of 17 early gastric carcinomas, of which 8 were pure intramucosal and 9 were infiltrating into the submucosa. We found an aneuploid DNA-stemline in 8 (47%) early gastric cancers, more often in tumours invading into the submucosa (5/9) than in purely mucosal tumours (3/8). Multiple DNA-stemlines were found more frequently in submucosally infiltrating tumours (4/5). These results confirm the presence of DNA-aneuploid early gastric carcinoma which are frequently heterogeneous and suggest that heterogeneity occurs more frequently in tumours invading the submucosa. This heterogeneity is best detected by analysing multiple samples of tumours for DNA-ploidy.     

Investigations on the variability of four genetic serum protein markers in Poland.

198 unrelated male and female Poles from Ostrów Wielkopolski (Central Poland) and 228 unrelated male and female Kashubes from Ko?cierzyna (Northern Poland) have been typed for four polymorphic serum protein systems: HP, TF, GC, and PI. Phenotype and allele frequencies of all these four polymorphic systems are quite different between Poles and Kashubes. Comparisons with some other Central and East European population samples (Slovaks, Hungarians, Matyos, Gypsies) revealed a considerable genetic heterogeneity among them. Genetic distance analysis showed that Hungarians and Matyos as well as Poles and Slovaks are found in two subclusters, which are linked up to one cluster. Gypsies and especially Kashubes exhibit a distinct position from this cluster. This genetic distance pattern can be explained satisfactorily considering the ethnohistory of the population groups under study.     

Population differences of aspartate aminotransferase and peptidase in the bay mussel Mytilus edulis

This investigation has demonstrated considerable heterogeneity among populations and some heterogeneity within populations in the distribution of alleles at two variant loci of Mytilus edulis. Although the causes of this variation remain obscure, some speculations have been made on the basis of available data. A cline for aspartate aminotransferase (AAT) alleles has been observed on the Pacific Coast. An immigration model has been proposed to explain the atypical ecological and genetic characteristics of large mussels found on Amchitka Island, Alaska. Marked differences were found in the distribution of peptidase alleles among collections from Southern California, the North Pacific Ocean, and New Jersey. Deviations from random distribution of phenotypes observed in comparisons made between large and small mussels from the New Jersey collection may reflect selection operating on these loci in this population.     

Growth regulation of the interstitial cell population in hydra. III. Interstitial cell density does not control stem cell proliferation

The interstitial cells of hydra contain a stem cell population which produces several classes of differentiated cell types. A model has been proposed which governs the growth rate of the interstitial cell population. This model, based on the density of interstitial cells in the tissue, makes specific predictions about the relationships among this density, the proportion of stem cells in the interstitial cell population, the growth rate of the interstitial cell population, and the amount of nematocyte differentiation. Hydroxyurea treatments were used to experimentally reduce interstitial cell numbers, and the validity of these expected correlations was tested. The results demonstrate that the predictions of the interstitial cell density model were not upheld. Furthermore, the findings suggest that the interstitial cells are a heterogeneous population, containing some cells which are no longer stem cells but which do retain a limited capacity for proliferation. In the following paper (S. Heimfeld and H.R. Bode, 1986, Dev. Biol. 115, 59-68) we have proposed an alternative mechanism to explain the observed correlations, which incorporates this heterogeneity into amplification divisions of interstitial cells already committed to differentiation.     

Molecular diversity after a range expansion in heterogeneous environments

Recent range expansions have probably occurred in many species, as they often happen after speciation events, after ice ages, or after the introduction of invasive species. While it has been shown that range expansions lead to patterns of molecular diversity distinct from those of a pure demographic expansion, the fact that many species do live in heterogeneous environments has not been taken into account. We develop here a model of range expansion with a spatial heterogeneity of the environment, which is modeled as a gamma distribution of the carrying capacities of the demes. By allowing temporal variation of these carrying capacities, our model becomes a new metapopulation model linking ecological parameters to molecular diversity. We show by extensive simulations that environmental heterogeneity induces a loss of genetic diversity within demes and increases the degree of population differentiation. We find that metapopulations with low average densities are much more affected by environmental heterogeneity than metapopulations with high average densities, which are relatively insensitive to spatial and temporal variations of the environment. Spatial heterogeneity is shown to have a larger impact on genetic diversity than temporal heterogeneity. Overall, temporal heterogeneity and local extinctions are not found to leave any specific signature on molecular diversity that cannot be produced by spatial heterogeneity.     

Individual heterogeneity in reproductive rates and cost of reproduction in a long‐lived vertebrate

Individual variation in reproductive success is a key feature of evolution, but also has important implications for predicting population responses to variable environments. Although such individual variation in reproductive outcomes has been reported in numerous studies, most analyses to date have not considered whether these realized differences were due to latent individual heterogeneity in reproduction or merely random chance causing different outcomes among like individuals. Furthermore, latent heterogeneity in fitness components might be expressed differently in contrasted environmental conditions, an issue that has only rarely been investigated. Here, we assessed (i) the potential existence of latent individual heterogeneity and (ii) the nature of its expression (fixed vs. variable) in a population of female Weddell seals (Leptonychotes weddellii), using a hierarchical modeling approach on a 30‐year mark–recapture data set consisting of 954 individual encounter histories. We found strong support for the existence of latent individual heterogeneity in the population, with “robust” individuals expected to produce twice as many pups as “frail” individuals. Moreover, the expression of individual heterogeneity appeared consistent, with only mild evidence that it might be amplified when environmental conditions are severe. Finally, the explicit modeling of individual heterogeneity allowed us to detect a substantial cost of reproduction that was not evidenced when the heterogeneity was ignored.     

Modeling the evolution of the human mitochondrial genome.

Mitochondrial DNA data have been used extensively to study evolution and early human origins. These applications require estimates of the rate at which nucleotide substitutions occur in the DNA sequence. We consider the problem of estimating substitution rates in the presence of site-to-site rate variation. A coalescent model is presented that allows for different substitution rates for purines and pyrimidines, as well as more detailed models that allow fast and slow rates within each of the purine and pyrimidine classes. A method for estimating such rates is presented. Even for these simple models of site heterogeneity, there are, typically, insufficient data to obtain reliable estimates of site-specific substitution rates. However, estimates of the average rate across all sites appear to be relatively stable even in the presence of site heterogeneity. Simulations of models with site-to-site variation in mutation rate show that hypervariable sites can produce peaks in the pairwise difference curves that have previously been attributed to population dynamics.     

Human immunodeficiency virus type 1 variability and long-term non-progression.

A high heterogeneity is found in the HIV-1 genome in vivo, not only between individuals, but also within a single individual. Different types of genetic heterogeneity of HIV-1 can be analyzed: the extension and the evolution of the viral quasispecies in blood, the variation between the virus obtained from different body compartment, the differences between isolates from diverse individuals and between HIV-1 subtypes. The virus population during primary HIV-1 infection is generally homogeneous and the intrahost viral evolution is thought to be forced (in absence of antiviral therapy) by the immune system pressure and is generally related to the length of the immunocompetent period. A group of 12 Italian and Swedish well characterized HIV-1 infected long-term nonprogressors (LNTP) have been analyzed for the viral heterogeneity, calculated in the nef gene and in the long terminal repeat (LTR). The intra-sample variations in LTNP were found comparable with those from 8 progressor patients, while a lower inter-individual diversity was observed in the former. In one LTNP the viral evolution during a four-years period was extremely low suggesting that other factors than the host immune pressure may be involved in modulating the intra- and inter-sample HIV-1 diversity.     

Immunoblotting technique to study release of melanophore-stimulating hormone from individual melanotrope cells of the intermediate lobe of Xenopus laevis.

The melanotrope cells in the pars intermedia in the pituitary of Xenopus laevis synthesize and release the melanophore-stimulating hormone (alpha MSH), a small peptide that causes skin darkening during the process of background adaptation. Evidence has been found for a heterogeneity in biosynthetic activity of the melanotrope cells. In the present study two questions were addressed: (1) does the melanotrope cell population also show heterogeneous alpha MSH-release, and (2) can this heterogeneity be changed by extracellular messengers? Since dopamine is known to inhibit alpha MSH-release, this messenger is used to study the regulation of the heterogeneity. To quantify alpha MSH-release from individual cells, a cell blotting procedure has been developed for the binding and relative quantification of the small alpha MSH peptide. The immunoblotting procedure involves binding of the cells to a carrier slide and binding of released alpha MSH to a nitrocellulose filter. After immunostaining, the amount of alpha MSH per cell was quantitated by image analysis. Untreated melanotrope cells reveal a distinct variability in alpha MSH-release, some cells showing low secretory activity, whereas others are strongly secreting, indicating heterogeneity of alpha MSH-release. Dopamine treatment strongly inhibits alpha MSH-release from individual cells, resulting in a clearly less pronounced melanotrope cell heterogeneity. The effect of dopamine appears to be dose-dependent as a low dopamine concentration has only a moderate effect on the alpha MSH-release. It is proposed that dopamine is a physiological regulator of the degree of melanotrope cell heterogeneity in alpha MSH-release.     

New data on coat color gene frequencies in cats: 1. the Armavir population

The population of domestic cats from the city of Armavir has been examined. A high frequency of gene O was revealed in the population. Differences among three subpopulations estimated using two genetic distances showed heterogeneity of the Armavir cat population. The extreme samples showed highly significant differences (P < 0.01; chi2[6] = 24.67), likely explained by the structural features of the synantropous population and human-driven frequency- dependent selection operating in it. The feline population of Armavir underwent significant changes during the past two decades. The d(ij) coefficient in it was 0.093; D(p) = 0.05. The frequencies of genes orange and Long-hair have increased in the general population. The frequency of gene dilution has decreased. These changes may have occurred because of genetic exchange with purebred domestic cats that have become more popular as pets in the recent years.     

Is heterogeneity of catchability in capture–recapture studies a mere sampling artifact or a biologically relevant feature of the population?

The heterogeneity of catchability (HC) among the individuals encountered during a capture–recapture study has long been regarded as a liability. However, heterogeneous capture probabilities may reflect interesting but hidden features of the population, such as social status. The difficulty is to distinguish between this intrinsic heterogeneity and the extrinsic heterogeneity induced by the study itself. So far, population ecologists have not been able to distinguish between these two sources of variation in capture heterogeneity because, in the presence of heterogeneity of capture in the data, they have frequently used a too simple approach. This traditional approach, which consists of incorporating two common sources of lack of fit (transience and trap-dependence), does not directly model the HC and thus cannot investigate its biological meaning. In this context, we propose, for open populations, to directly model the HC by employing multievent models. Multievent models make it possible to break HC into two classes of catchability viewed as uncertain states. With the introduction of a coefficient of heterogeneity to model proportional probabilities of capture over time in the two classes, our approach allows the investigation of HC in a parsimonious way. In this paper, we apply both this new approach and the traditional approach to a long-term data set of male deer mice Peromyscus maniculatus. We then compare 13 candidate models separately for each approach. Our results indicate that the new approach is superior to the traditional approach. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Scale-Dependent Effects of a Heterogeneous Landscape on Genetic Differentiation in the Central American Squirrel Monkey (Saimiri oerstedii)

Landscape genetic studies offer a fine-scale understanding of how habitat heterogeneity influences population genetic structure. We examined population genetic structure and conducted a landscape genetic analysis for the endangered Central American Squirrel Monkey (Saimiri oerstedii) that lives in the fragmented, human-modified habitats of the Central Pacific region of Costa Rica. We analyzed non-invasively collected fecal samples from 244 individuals from 14 groups for 16 microsatellite markers. We found two geographically separate genetic clusters in the Central Pacific region with evidence of recent gene flow among them. We also found significant differentiation among groups of S. o. citrinellus using pairwise F(ST) comparisons. These groups are in fragments of secondary forest separated by unsuitable "matrix" habitats such as cattle pasture, commercial African oil palm plantations, and human residential areas. We used an individual-based landscape genetic approach to measure spatial patterns of genetic variance while taking into account landscape heterogeneity. We found that large, commercial oil palm plantations represent moderate barriers to gene flow between populations, but cattle pastures, rivers, and residential areas do not. However, the influence of oil palm plantations on genetic variance was diminished when we restricted analyses to within population pairs, suggesting that their effect is scale-dependent and manifests during longer dispersal events among populations. We show that when landscape genetic methods are applied rigorously and at the right scale, they are sensitive enough to track population processes even in species with long, overlapping generations such as primates. Thus landscape genetic approaches are extremely valuable for the conservation management of a diverse array of endangered species in heterogeneous, human-modified habitats. Our results also stress the importance of explicitly considering the heterogeneity of matrix habitats in landscape genetic studies, instead of assuming that all matrix habitats have a uniform effect on population genetic processes.     

Complex segregation analysis of Parkinson's disease in the Finnish population

The risk of Parkinson's disease (PD) is higher among relatives of affected individuals than among other members of the population, and most family studies have suggested autosomal dominant inheritance, although both autosomal dominant and recessive susceptibility genes have recently been identified. We carried out a complex segregation analysis with POINTER to assess the mode of inheritance of PD in the population of northern Finland. Nuclear families (n=265) were identified through a proband with idiopathic PD. The analysis was first carried out for the total data set, and then the heterogeneity between early-onset (proband under 55 years at onset) and late-onset families was examined. Finally, families with more than one affected individual were analyzed separately. The sporadic model was rejected (P<0.0001). Significant heterogeneity was found between the early-onset and late-onset families, suggesting that major genes have a greater role in early-onset PD than in late-onset PD and that the etiology of idiopathic PD is heterogeneous, even in the Finnish population, which has evolved from a small group of founders. The analysis of familial PD supported the hypothesis that a major locus was present in this subset, but it was not possible to distinguish between a recessive model with a high penetrance and a dominant model with lower penetrance.