Genetic diversity of microsatellite loci in hierarchically structured populations

Microsatellite loci are widely used for investigating patterns of genetic variation within and among populations. Those patterns are in turn determined by population sizes, migration rates, and mutation rates. We provide exact expressions for the first two moments of the allele frequency distribution in a stochastic model appropriate for studying microsatellite evolution with migration, mutation, and drift under the assumption that the range of allele sizes is bounded. Using these results, we study the behavior of several measures related to Wright’s F_ST, including Slatkin’s R_ST. Our analytical approximations for F_ST and R_ST show that familiar relationships between N_em and F_ST or R_ST hold when the migration and mutation rates are small. Using the exact expressions for F_ST and R_ST, our numerical results show that, when the migration and mutation rates are large, these relationships no longer hold. Our numerical results also show that the diversity measures most closely related to F_ST depend on mutation rates, mutational models (stepwise versus two-phase), migration rates, and population sizes. Surprisingly, R_ST is relatively insensitive to the mutation rates and mutational models. The differing behaviors of R_ST and F_ST suggest that properties of the among-population distribution of allele frequencies may allow the roles of mutation and migration in producing patterns of diversity to be distinguished, a topic of continuing investigation.     

Population differentiation and migration: coalescence times in a two-sex island model for autosomal and X-linked loci

Evolutionists have debated whether population-genetic parameters, such as effective population size and migration rate, differ between males and females. In humans, most analyses of this problem have focused on the Y chromosome and the mitochondrial genome, while the X chromosome has largely been omitted from the discussion. Past studies have compared F_ST values for the Y chromosome and mitochondrion under a model with migration rates that differ between the sexes but with equal male and female population sizes. In this study we investigate rates of coalescence for X-linked and autosomal lineages in an island model with different population sizes and migration rates for males and females, obtaining the mean time to coalescence for pairs of lineages from the same deme and for pairs of lineages from different demes. We apply our results to microsatellite data from the Human Genome Diversity Panel, and we examine the male and female migration rates implied by observed F_ST values.     

Understanding evolutionary and ecological dynamics using a continuum limit

Continuum limits in the form of stochastic differential equations are typically used in theoretical population genetics to account for genetic drift or more generally, inherent randomness of the model. In evolutionary game theory and theoretical ecology, however, this method is used less frequently to study demographic stochasticity. Here, we review the use of continuum limits in ecology and evolution. Starting with an individual‐based model, we derive a large population size limit, a (stochastic) differential equation which is called continuum limit. By example of the Wright–Fisher diffusion, we outline how to compute the stationary distribution, the fixation probability of a certain type, and the mean extinction time using the continuum limit. In the context of the logistic growth equation, we approximate the quasi‐stationary distribution in a finite population.     

Dynamics of neutral and selected alleles when the offspring distribution is skewed

We analyze the dynamics of two alternative alleles in a simple model of a population that allows for large family sizes in the distribution of offspring number. This population model was first introduced by Eldon and Wakeley, who described the backward-time genealogical relationships among sampled individuals, assuming neutrality. We study the corresponding forward-time dynamics of allele frequencies, with or without selection. We derive a continuum approximation, analogous to Kimura's diffusion approximation, and we describe three distinct regimes of behavior that correspond to distinct regimes in the coalescent processes of Eldon and Wakeley. We demonstrate that the effect of selection is strongly amplified in the Eldon-Wakeley model, compared to the Wright-Fisher model with the same variance effective population size. Remarkably, an advantageous allele can even be guaranteed to fix in the Eldon-Wakeley model, despite the presence of genetic drift. We compute the selection coefficient required for such behavior in populations of Pacific oysters, based on estimates of their family sizes. Our analysis underscores that populations with the same effective population size may nevertheless experience radically different forms of genetic drift, depending on the reproductive mechanism, with significant consequences for the resulting allele dynamics.     

Sterol chemical configuration and conformation influence the thermotropic phase behaviour of dipalmitoylphosphatidylcholine mixtures containing 5β-cholestan-3β- and -3α-ol

We report here our differential scanning calorimetry measurements investigating the thermotropic phase behaviour of binary dipalmitoylphosphatidylcholine (DPPC)/sterol mixtures containing two saturated sterols with different ring configurations (5β-H and either 3α-OH or 3β-OH). These measurements differ in the proportions of sharp and broad components in the heating endotherms, representing the melting of the sterol-poor and sterol-rich lipid micro-domains of the DPPC bilayer, respectively. Our results suggest that the 5,10-cis ring configuration of both saturated sterols and the ring A conformations have the greatest influence on DPPC bilayer properties, most likely by inducing small increases in the mean area/molecule as compared to cholesterol. However, the C3-OH orientation also influences sterol miscibility, likely due to variations in the strength and number of interfacial H-bonds with changes in molecular area, which in turn probably reflect the depth of the sterol in the DPPC bilayer. This influence of C3-OH orientation is significantly greater than was observed in our earlier study of cholesterol/- and epicholesterol/DPPC mixtures. Overall, our results show that both saturated and unsaturated 3α-ols are less miscible than the corresponding 3β-ols, but that the presence of a Δ⁵ double bond can improve the sterol miscibility in the DPPC bilayer at high sterol concentrations.     

Drawing inferences about the coancestry coefficient

The coancestry coefficient, also known as the population structure parameter, is of great interest in population genetics. It can be thought of as the intraclass correlation of pairs of alleles within populations and it can serve as a measure of genetic distance between populations. For a general class of evolutionary models it determines the distribution of allele frequencies among populations. Under more restrictive models it can be regarded as the probability of identity by descent of any pair of alleles at a locus within a random mating population. In this paper we review estimation procedures that use the method of moments or are maximum likelihood under the assumption of normally distributed allele frequencies. We then consider the problem of testing hypotheses about this parameter. In addition to parametric and non-parametric bootstrap tests we present an asymptotically-distributed chi-square test. This test reduces to the contingency-table test for equal sample sizes across populations. Our new test appears to be more powerful than previous tests, especially for loci with multiple alleles. We apply our methods to HapMap SNP data to confirm that the coancestry coefficient for humans is strictly positive.     

Transmission dynamics of Toxoplasma gondii along an urban-rural gradient

Recently, several authors have proposed that the availability of intermediate hosts (IHs) for definitive hosts (DHs) may contribute to determining the dynamics and evolutionary ecology of parasites with facultative complex life cycles. The protozoa Toxoplasma gondii may be transmitted to DHs either via predation of infected IHs through a complex life cycle (CLC) or directly from a contaminated environment through a simple life cycle (SLC). This parasite is also present in contrasting host density environments. We tested the hypothesis that the relative contributions of the CLC and SLC along an urban-rural gradient depend on the IH supply. We built and analysed a deterministic model of the T. gondii transmission cycle. The SLC relative contribution is important only in urban-type environments, i.e., with low predation rate on IHs. In contrast, the parasite is predominantly transmitted through a CLC in suburban and rural environments. The association of the two cycles enables the parasite to spread in situations of low IH availability and low DH population size for which each cycle alone is insufficient.     

Antioxidant protective effect of flavonoids on linoleic acid peroxidation induced by copper(II)/ascorbic acid system

Antioxidants are compounds that can delay or inhibit lipid oxidation. The peroxidation of linoleic acid (LA) in the absence and presence of Cu(II) ion–ascorbate combinations was investigated in aerated and incubated emulsions at 37 °C and pH 7. LA peroxidation induced by copper(II)–ascorbic acid system followed first order kinetics with respect to hydroperoxides concentration. The extent of copper-initiated peroxide production in a LA system assayed by ferric thiocyanate method was used to determine possible antioxidant and prooxidant activities of the added flavonoids. The effects of three different flavonoids of similar structure, i.e. quercetin (QR), morin (MR) and catechin (CT), as potential antioxidant protectors were studied in the selected peroxidation system. The inhibitive order of flavonoids in the protection of LA peroxidation was: morin > catechin ≥ quercetin, i.e. agreeing with that of formal reduction potentials versus NHE at pH 7, i.e. 0.60, 0.57 and 0.33 V for MR, CT, and QR, respectively. Morin showed antioxidant effect at all concentrations whereas catechin and quercetin showed both antioxidant and prooxidant effects depending on their concentrations. The structural requirements for antioxidant activity in flavonoids interestingly coincide with those for Cu(II)-induced prooxidant activity, because as the reducing power of a flavonoid increases, Cu(II)–Cu(I) reduction is facilitated that may end up with the production of reactive species. The findings of this study were evaluated in the light of structure–activity relationships of flavonoids, and the results are believed to be useful to better understand the actual conditions where flavonoids may act as prooxidants in the preservation of heterogeneous food samples containing traces of transition metal ions.     

Temporal variation of allele frequencies in a natural population of wild Vigna unguiculata

Abstract

Temporal variation in allele frequencies in a natural population of wild Vigna unguiculata was studied by making monthly collections of seeds over a two-year period. Using starch gel electrophoresis, four out of seven loci analysed were shown to be polymorphic (Enp, Fdh, Fle₃ and Pgd₂ ). These four loci showed significant variation in allele frequencies over time. Changes in population structure over time were analysed using F-statistic estimators. Although heterogeneity was evident between loci, the analysis showed significant differentiation among months within a year for all polymorphic loci. Fixation indexes were all positive and statistically different from zero, highlighting a significant departure from random mating. Using analysis of variance (ANOVA), the pattern of inbreeding (f) showed significant changes over time (season); among the polymorphic loci, Enp most strongly contributed to this significance. Significant correlations were found between allele frequencies at different loci. The monthly average gene diversity (He) and allele frequencies at the Enp locus were found to be significantly correlated with weather conditions (temperature and rainfall distribution). These allele frequency deviations over time can be attributed to changes in pollinator behaviour, and frequent genetic bottlenecks that are associated with changes in environmental conditions.     

Melanoblast proliferation dynamics during mouse embryonic development. Modeling and validation

In this paper, we are looking for mathematical modeling of mouse embryonic melanoblast proliferation dynamics, taking into account, the expression level of β‐catenin. This protein plays an important role into the whole signal pathway process. Different assumptions on some unobservable features lead to different candidate models. From real data measured, from biological experiments and from a priori biological knowledge, it was able to validate or invalidate some of the candidate models. Data assimilation and parameter identification allowed us to derive a mathematical model that is in very good agreement with biological data. As a result, the produced model can give tracks for biologists into their biological investigations and experimental evidence. Another interest is the use of this model for robust hidden parameter identification like double times or number of founder melanoblasts.     

A coalescent dual process in a Moran model with genic selection

A coalescent dual process for a multi-type Moran model with genic selection is derived using a generator approach. This leads to an expansion of the transition functions in the Moran model and the Wright–Fisher diffusion process limit in terms of the transition functions for the coalescent dual. A graphical representation of the Moran model (in the spirit of Harris) identifies the dual as a strong dual process following typed lines backwards in time. An application is made to the harmonic measure problem of finding the joint probability distribution of the time to the first loss of an allele from the population and the distribution of the surviving alleles at the time of loss. Our dual process mirrors the Ancestral Selection Graph of [Krone, S. M., Neuhauser, C., 1997. Ancestral processes with selection. Theoret. Popul. Biol. 51, 210–237; Neuhauser, C., Krone, S. M., 1997. The genealogy of samples in models with selection. Genetics 145, 519–534], which allows one to reconstruct the genealogy of a random sample from a population subject to genic selection. In our setting, we follow [Stephens, M., Donnelly, P., 2002. Ancestral inference in population genetics models with selection. Aust. N. Z. J. Stat. 45, 395–430] in assuming that the types of individuals in the sample are known. There are also close links to [Fearnhead, P., 2002. The common ancestor at a nonneutral locus. J. Appl. Probab. 39, 38–54]. However, our methods and applications are quite different. This work can also be thought of as extending a dual process construction in a Wright–Fisher diffusion in [Barbour, A.D., Ethier, S.N., Griffiths, R.C., 2000. A transition function expansion for a diffusion model with selection. Ann. Appl. Probab. 10, 123–162]. The application to the harmonic measure problem extends a construction provided in the setting of a neutral diffusion process model in [Ethier, S.N., Griffiths, R.C., 1991. Harmonic measure for random genetic drift. In: Pinsky, M.A. (Ed.), Diffusion Processes and Related Problems in Analysis, vol. 1. In: Progress in Probability Series, vol. 22, Birkhäuser, Boston, pp. 73–81].     

The role of low avidity T cells in the protection against type 1 diabetes: a modeling investigation

Cytotoxic T lymphocytes (CTLs) play a dominant role in the pathogenesis of autoimmune diabetes, commonly denoted Type 1 Diabetes (T1D). These CTLs (notably CD8⁺ T cells) recognize and kill insulin-secreting pancreatic β cells, reducing their number by ∼90%. The resulting reduction of insulin secretion causes the defective regulation of glucose metabolism, leading to the characteristic symptoms of diabetes. Recognition of β cells as targets by CTLs depends on the interactions between MHC-peptide complexes on the surface of β cells and receptors (TCRs) on T cells. Those CTLs with high affinity TCRs (also called high avidity T cells) cause most of the harm, while those with low affinity TCRs (also called low avidity T cells) play a more mysterious role. Recent experimental evidence suggests that low avidity T cells accumulate as memory T cells during the disease and may be protective in NOD mice (a strain prone to developing T1D), delaying disease progression. It has been hypothesized that such low avidity T cells afford disease protection either by crowding the islets of Langerhans, where β cells reside, or by killing antigen presenting cells (APCs).In this paper, we explore the hypothesized mechanisms for this protective effect in the context of a series of models for (1) the interactions of low and high avidity T cells, (2) the effect of APCs and (3) the feedback from β cell killing to autoantigen-induced T cell proliferation. We analyze properties of these models, noting consistency of predictions with observed behaviour. We then use the models to examine the influence of various treatment strategies on the progression of the disease. The model reveals that progressive accumulation of memory low avidity autoreactive T cells during disease progression makes treatments aimed at expanding these protective T cell types more effective close to, or at the onset of clinical disease. It also provides evidence for the hypothesis that low avidity T cells kill APCs (rather than the alternate hypothesis that they crowd the islets).     

The shared reward dilemma

One of the most direct human mechanisms of promoting cooperation is rewarding it. We study the effect of sharing a reward among cooperators in the most stringent form of social dilemma, namely the prisoner's dilemma (PD). Specifically, for a group of players that collect payoffs by playing a pairwise PD game with their partners, we consider an external entity that distributes a fixed reward equally among all cooperators. Thus, individuals confront a new dilemma: on the one hand, they may be inclined to choose the shared reward despite the possibility of being exploited by defectors; on the other hand, if too many players do that, cooperators will obtain a poor reward and defectors will outperform them. By appropriately tuning the amount to be shared a vast variety of scenarios arises, including the traditional ones in the study of cooperation as well as more complex situations where unexpected behavior can occur. We provide a complete classification of the equilibria of the n-player game as well as of its evolutionary dynamics.     

A statistical framework for genetic association studies of power curves in bird flight

How the power required for bird flight varies as a function of forward speed can be used to predict the flight style and behavioral strategy of a bird for feeding and migration. A U-shaped curve was observed between the power and flight velocity in many birds, which is consistent to the theoretical prediction by aerodynamic models. In this article, we present a general genetic model for fine mapping of quantitative trait loci (QTL) responsible for power curves in a sample of birds drawn from a natural population. This model is developed within the maximum likelihood context, implemented with the EM algorithm for estimating the population genetic parameters of QTL and the simplex algorithm for estimating the QTL genotype-specific parameters of power curves. Using Monte Carlo simulation derived from empirical observations of power curves in the European starling (Sturnus vulgaris), we demonstrate how the underlying QTL for power curves can be detected from molecular markers and how the QTL detected affect the most appropriate flight speeds used to design an optimal migration strategy. The results from our model can be directly integrated into a conceptual framework for understanding flight origin and evolution.     

Relevant genetic differentiation among Brazilian populations of Anastrepha fraterculus (Diptera,Tephritidae)

We used a population genetic approach to detect the presence of genetic diversity among six populations of Anastrepha fraterculus across Brazil. To this aim, we used Simple Sequence Repeat (SSR) markers, which may capture the presence of differentiative processes across the genome in distinct populations. Spatial analyses of molecular variance were used to identify groups of populations that are both genetically and geographically homogeneous while also being maximally differentiated from each other. The spatial analysis of genetic diversity indicates that the levels of diversity among the six populations vary significantly on an eco-geographical basis. Particularly, altitude seems to represent a differentiating adaptation, as the main genetic differentiation is detected between the two populations present at higher altitudes and the other four populations at sea level. The data, together with the outcomes from different cluster analyses, identify a genetic diversity pattern that overlaps with the distribution of the known morphotypes in the Brazilian area.     

Ecomorphology of the giant bear-dogs Amphicyon and Ischyrocyon

Giant bear-dogs of the genera Amphicyon and Ischyrocyon (Carnivora, Amphicyonidae, Amphicyoninae) were the largest carnivorans in North America during middle and late Miocene (17.5–8.8 Mya) with a dental and skeletal morphology that combined features found in living Ursidae, Canidae, and Felidae. This study tests previously proposed models of diet and hunting behaviour of these extinct carnivorans. Relative grinding area (RGA) of lower molars and wear pattern on upper molars suggest that bear-dogs were carnivorous. Amphicyon and Ischyrocyon possessed skeletal features of both ambush (short distal limb segments) and pursuit (caudally bent olecranon process of ulna) living predators. Therefore, bear-dogs probably pursued their prey (mediportal ungulates) for a longer distance but at a slower speed than do living ambush predators. Upon catching up to its prey a bear-dog probably seized it with powerfully muscled forelimbs and killed it by tearing into its ribcage or neck with canines set in a narrow rostrum.     

Weak convergence of discrete time non-markovian processes related to selection models in population genetics

We consider discrete time stochastic processes defined by solutions to some non-linear difference equations whose coefficients are autocorrelated random sequences. It is proved that these processes converge weakly in D[0, T] to diffusion processes, under the assumption that the random sequences satisfy some mixing condition. Diffusion approximation for stochastic selection models in population genetics is discussed, as the application of this limit theorem.     

Agrobacterium-mediated genetic transformation of plants: The role of host

Agrobacterium-mediated genetic transformation is the most widely used technology to obtain overexpression of recombinant proteins in plants. Molecular events that occur within Agrobacterium during interactions with host plants have been studied extensively, and now we have a reasonable understanding the key factors involved in the regulation of T-DNA nuclear import and genomic integration. By contrast, very little is known about the events that take place in the host cells during genetic transformation by Agrobacterium. Here, we describe the plant-related factors including genotype, genes, proteins, competency of target tissues and phenolic compounds that participate in Agrobacterium-mediated genetic transformation and discuss their possible roles in this process. Because Agrobacterium probably adapts existing cellular processes for its life cycle, identifying the processes in host cells during Agrobacterium infection might contribute to better understanding of basic biological processes as cell communication, intracellular transport and DNA repair and recombination as well as to expanding the host range of Agrobacterium as a genetic engineering tool.     

Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage

A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of P2Y₆ receptors activated by the ubiquitous signaling nucleotide uridine 5’-diphosphate is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine 5’-diphosphate and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty.