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At least 379 records · Page 21Linked to original sources
PubMed2003

Population-genetic models of the fates of duplicate genes.

The ultimate fate of a duplicated gene is that it either silenced through inactivating mutations or both copies are maintained by selection. This later fate can occur via neofunctionalization wherein one copy acquires a new function or by subfunctionalization wherein the original function of the gene is partitioned across both copies. The relative probabilities of these three different fates involve often very subtle iterations between of population size, mutation rate, and selection. All three of these fates are critical to the expansion and diversification of gene families.

Evolution, Molecular↗
PubMed2002

Genetic modelling of the estrogen metabolism as a risk factor of hormone-dependent disorders.

Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for developing breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for developing prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and the development of endometrial, prostate, and breast cancer. Available data indicate that the protective effect against breast cancer of a later age at menarche is limited to wild-type CYP 17 allele carriers. Among women with the polycystic ovary syndrome, carriage of mutant CYP 17 alleles is sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for developing breast cancer, advanced breast cancer stages, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to genes that encode estrogen-metabolizing enzymes as strong hereditary determinants of the susceptibility to benign as well as malignant conditions.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Canalization, genetic assimilation and preadaptation. A quantitative genetic model.

We propose a mathematical model to analyze the evolution of canalization for a trait under stabilizing selection, where each individual in the population is randomly exposed to different environmental conditions, independently of its genotype. Without canalization, our trait (primary phenotype) is affected by both genetic variation and environmental perturbations (morphogenic environment). Selection of the trait depends on individually varying environmental conditions (selecting environment). Assuming no plasticity initially, morphogenic effects are not correlated with the direction of selection in individual environments. Under quite plausible assumptions we show that natural selection favors a system of canalization that tends to repress deviations from the phenotype that is optimal in the most common selecting environment. However, many experimental results, dating back to Waddington and others, indicate that natural canalization systems may fail under extreme environments. While this can be explained as an impossibility of the system to cope with extreme morphogenic pressure, we show that a canalization system that tends to be inactivated in extreme environments is even more advantageous than rigid canalization. Moreover, once this adaptive canalization is established, the resulting evolution of primary phenotype enables substantial preadaptation to permanent environmental changes resembling extreme niches of the previous environment.

Adaptation, Physiological↗
PubMed1982

Population genetic models in the study of aging and longevity in a Mennonite community.

This is a preliminary report on a 3-year multidisciplinary study of aging among historically and genetically related Mennonite congregations in Kansas and Nebraska. Three aspects of longevity and aging are examined: (1) the relationship of heterozygosity to survivorship using 8 genetic blood group loci, (2) changes in taste sensitivity with age using 14 dilutions of PTC; and (3) life span correlations among parents and offspring during a 100 year period. Heterozygosity was found to be independent of survivorship. No diminution in taste sensitivity to PTC was found with increasing age although a significant difference in PTC taste thresholds was found between males and females. No relationship was found between nontasters and individuals with a history of thyroid disease. Mother's life span was found to correlate more closely with daughter than any other familial correlation.

Adolescent↗
PubMed1997

Population genetics models of transposable elements.

The control of transposable element copy number is of considerable theoretical and empirical interest. Under simple models, copy numbers may increase without limit. Mechanisms that can prevent such an increase include those in which the effect of selection increases with copy number, those in which the rate of transposition decreases with copy number, and those where unlimited increase in copy number is prevented by the consequences of functional heterogeneity in the transposable element family. Finite population sizes may attenuate the power of natural selection to act on transposable element copy number in a number of ways that may be of particular importance in laboratory populations. First, a small host population size will create occasional periods in which the variance between individuals in copy number is diminished, and with it the power of natural selection, even when the expected variance is Poisson. Second, small population sizes will produce high-frequency transposable element sites, systematically reducing the variance in copy number. The consequences will be particularly profound when the selective damage of transposable elements follows from their heterozygosity, as when ectopic exchange limits copy number.

Animals↗
PubMed2003

Caenorhabditis elegans: an emerging genetic model for the study of innate immunity.

Invaluable insights into how animals, humans included, defend themselves against infection have been provided by more than a decade of genetic studies that have used fruitflies. In the past few years, attention has also turned to another simple animal model, the nematode worm Caenorhabditis elegans. What exactly have we learned from the work in Drosophila? And will research with C. elegans teach us anything new about our response to pathogen attack?

Animals↗
PubMed1989

A genetic model of interpopulation variation and covariation of quantitative characters.

Evolutionary consequences of natural selection, migration, genotype-environment interaction, and random genetic drift on interpopulation variation and covariation of quantitative characters are analysed in terms of a selection model that partitions natural selection into directional and stabilizing components. Without migration, interpopulation variation and covariation depend mainly on the pattern and intensities of selection among populations and the harmonic mean of effective population sizes. Both transient and equilibrium covariance structures are formulated with suitable approximations. Migration reduces the differentiation among populations, but its effect is less with genotype-environment interaction. In some special cases of genotype-environment interaction, the equilibrium interpopulation variation and covariation is independent of migration.

Environment↗
PubMed2005

Quantitative genetic models of sexual conflict based on interacting phenotypes.

Evolutionary conflict arises between reproductive partners when alternative reproductive opportunities are available. Sexual conflict can generate sexually antagonistic selection, which mediates sexual selection and intersexual coevolution. However, despite intense interest, the evolutionary implications of sexual conflict remain unresolved. We propose a novel theoretical approach to study the evolution of sexually antagonistic phenotypes based on quantitative genetics and the measure of social selection arising from male-female interactions. We consider the phenotype of one sex as both a genetically influenced evolving trait as well as the (evolving) social environment in which the phenotype of the opposite sex evolves. Several important points emerge from our analysis, including the relationship between direct selection on one sex and indirect effects through selection on the opposite sex. We suggest that the proposed approach may be a valuable tool to complement other theoretical approaches currently used to study sexual conflict. Most importantly, our approach highlights areas where additional empirical data can help clarify the role of sexual conflict in the evolutionary process.

Animals↗
PubMed1999

A genetic model for human polyglutamine-repeat disease in Drosophila melanogaster.

To apply genetics to the problem of human polyglutamine-repeat disease, we recreated polyglutamine-repeat disease in Drosophila melanogaster. To do this, we expressed forms of the human gene encoding spinocerebellar ataxia type 3, also called Machado-Joseph disease (SCA-3/MJD). This gene is responsible for the most common form of human ataxia worldwide. Expression of a normal form of the MJD protein with 27 polyglutamines (MJDtr-Q27) had no phenotype. However, expression of a form of the protein with an expanded run of 78 glutamines (MJDtr-Q78) caused late onset progressive degeneration. In addition, the MJDtr-Q78 formed abnormal protein aggregates, or nuclear inclusions (NIs), whereas the control protein was cytoplasmic. These data indicate that the mechanisms of human polyglutamine-repeat disease are conserved to Drosophila. We are currently using this model to address potential mechanisms by which the mutant disease protein causes neural degeneration, as well as to define genes that can prevent polyglutamine-induced degeneration. By applying the power of Drosophila genetics to the problem of human polyglutamine-induced neural degeneration, we hope to identify ways to prevent and treat these diseases in humans.

Animals↗
PubMed1991

Ecological and genetic models of host-pathogen coevolution.

A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution.

Biological Evolution↗
PubMed2002

An improved genetic model generates high-resolution mapping of QTL for protein quality in maize endosperm.

The genetic mapping of polymorphic markers in a cross between two inbred plant lines has proven to be a powerful method for detecting quantitative trait loci (QTL) underlying complex traits. However, existing methods of QTL mapping were developed for disomic inheritance of both marker and QTL loci in a diploid population. To map QTL influencing traits expressed in the endosperm, a triploid embryo-nourishing tissue resulting from double fertilization, existing QTL mapping models require modification to consider the trisomic inheritance of the endosperm and the generation difference between the mapping population and the endosperm. Such a model requires simultaneous use of two successive generations, which theoretically can lead to an increase in resolution for QTL mapping compared with the use of a single backcross or F(2) generation. Using a newly developed model based on these considerations, we demonstrate the improved resolution of QTL, influencing protein quality traits in maize endosperm. The increased resolution made possible with this approach makes identified QTL accessible to positional cloning.

Chromosome Mapping↗
PubMed2004

Genetic models of mechanotransduction: the nematode Caenorhabditis elegans.

Mechanotransduction, the conversion of a mechanical stimulus into a biological response, constitutes the basis for a plethora of fundamental biological processes such as the senses of touch, balance, and hearing and contributes critically to development and homeostasis in all organisms. Despite this profound importance in biology, we know remarkably little about how mechanical input forces delivered to a cell are interpreted to an extensive repertoire of output physiological responses. Recent, elegant genetic and electrophysiological studies have shown that specialized macromolecular complexes, encompassing mechanically gated ion channels, play a central role in the transformation of mechanical forces into a cellular signal, which takes place in mechanosensory organs of diverse organisms. These complexes are highly efficient sensors, closely entangled with their surrounding environment. Such association appears essential for proper channel gating and provides proximity of the mechanosensory apparatus to the source of triggering mechanical energy. Genetic and molecular evidence collected in model organisms such as the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse highlight two distinct classes of mechanically gated ion channels: the degenerin (DEG)/epithelial Na(+) channel (ENaC) family and the transient receptor potential (TRP) family of ion channels. In addition to the core channel proteins, several other potentially interacting molecules have in some cases been identified, which are likely parts of the mechanotransducing apparatus. Based on cumulative data, a model of the sensory mechanotransducer has emerged that encompasses our current understanding of the process and fulfills the structural requirements dictated by its dedicated function. It remains to be seen how general this model is and whether it will withstand the impiteous test of time.

Animals↗
PubMed2000

Alterations in neuronal gamma-aminobutyric acid(A) receptor responsiveness in genetic models of seizure susceptibility with different expression patterns.

The genetically epilepsy-prone rat (GEPR) is a unique animal model of seizure predisposition with substrains (i.e., GEPR-NE, GEPR-3, and GEPR-9) that exhibit different seizure patterns in response to the same stimulus. Among many deficits identified in these animals, reduced responses to GABA(A) receptor agonists have been described in several brain regions of the GEPR-9. However, few studies have quantitatively analyzed this difference in responsiveness or have examined and compared the responsiveness of GEPR-3 neurons with the other strains. Using intracellular recording, we determined and compared the responsiveness of Purkinje neurons from GEPR-3 animals with those of control (both Sprague-Dawley and GEPR-NE) and GEPR-9 rats at different developmental ages. In GEPR-9 animals, the EC(50) value for GABA and muscimol was shifted 3-fold to the right, with no reduction in maximum. In contrast, GEPR-3 animals showed a significant reduction in the maximum hyperpolarizing response to only GABA and muscimol with no change in the EC(50) values. Responsiveness to glutamate, aspartate, norepinephrine, and diazepam was unchanged in both strains, indicating that the change in responsiveness was highly selective for GABA(A) receptor agonists. Changes in responsiveness in animals <15 days of age suggests that deficits in GABAergic function exist before the development of seizure susceptibility. In addition, the data are the first to reveal that the GEPR-3 and GEPR-9 exhibit different changes in GABA(A) receptor function and may provide significant insight into the cellular mechanism underlying differences between these two strains.

Age Factors↗
PubMed2000

Competitive speciation in quantitative genetic models.

We study sympatric speciation due to competition in an environment with a broad distribution of resources. We assume that the trait under selection is a quantitative trait, and that mating is assortative with respect to this trait. Our model alternates selection according to Lotka-Volterra-type competition equations, with reproduction using the ideas of quantitative genetics. The recurrence relations defined by these equations are studied numerically and analytically. We find that when a population enters a new environment, with a broad distribution of unexploited food sources, the population distribution broadens under a variety of conditions, with peaks at the edge of the distribution indicating the formation of subpopulations. After a long enough time period, the population can split into several subpopulations with little gene flow between them.

Animals↗