James W Curtsinger - US grants

genetic models; model design /development; gene frequency; population genetics; molecular genetics; mathematical model; computer simulation; alleles;

The classical foundations of deterministic theoretical population genetics are Wright's "mean fitness principle" and Fisher's "fundamental theorem," which govern the dynamics of one-locus viability selection models. The P.I. has developed an analytical method for generating Lyapunov functions for a more general class of models incorporating frequency dependent selection. Specifically, general dynamic rules have been derived for models with selection in both prezygotic and zygotic stages, and for models in which fitness is a polynomial function of allelic frequency of arbitrary positive degree. Further development and application of the analytic method will concentrate on four types of models of general interest to evolutionary biologists: (1) Mixed models involving prezygotic, zygotic, sexual, and fertility selection; (2) Multiple allelic models in which non-monotone covergence occurs for some fitness sets and initial conditions; (3) Cases in which social interaction of pair-wise or higher order influences viability; (4) Mechanisms of molecular turnover which exhibit a formal analogy with meiotic drive models. The proposed research will provide general evolutionary principles for broad classes of models generally acknowledged to be of biological importance, but where present theoretical understanding is very limited. Most significantly, the proposed line of research offers a method for unifying many special cases in population genetics theory.

genetic models; model design /development; gene frequency; population genetics; molecular genetics; mathematical model; computer simulation; alleles;

population genetics; genetic regulation; molecular genetics; biochemical evolution; gene expression; animal population density; natural selections; clinical biomedical equipment; biomedical automation; pleiotropism; gene frequency; statistics /biometry; Drosophilidae;

The classical foundations of deterministic theoretical population genetics are Wright's "mean fitness principle" and Fisher's "fundamental theorem," which govern the dynamics of one-locus viability selection models. The P.I. has developed an analytical method for generating Lyapunov functions for a more general class of models incorporating frequency dependent selection. Specifically, general dynamic rules have been derived for models with selection in both prezygotic and zygotic stages, and for models in which fitness is a polynomial function of allelic frequency of arbitrary positive degree. Further development and application of the analytic method will concentrate on four types of models of general interest to evolutionary biologists: (1) Mixed models involving prezygotic, zygotic, sexual, and fertility selection; (2) Multiple allelic models in which non-monotone covergence occurs for some fitness sets and initial conditions; (3) Cases in which social interaction of pair-wise or higher order influences viability; (4) Mechanisms of molecular turnover which exhibit a formal analogy with meiotic drive models. The proposed research will provide general evolutionary principles for broad classes of models generally acknowledged to be of biological importance, but where present theoretical understanding is very limited. Most significantly, the proposed line of research offers a method for unifying many special cases in population genetics theory.

High Pressure Liquid Chromatography allows the quantitative analysis of many biologically important materials like derivatized amino acids, oligopeptides, phenolics, polar terpenoids, and coumarin allelochemicals that are too heavy for gas chromatographic separation. The proposed HPLC system will support the research of at least five faculty lab groups in the new University of Minnesota Ecology Building, including investigations of plant/herbivore interactions and plant secondary products.

We propose to investigate mortality and morbidity at the oldest ages in Drosophila melanogaster, an experimental system that is well-suited to laboratory analysis and genetic manipulation. Specific aims are: 1) QTL Mapping- We will estimate the number, chromosomal location, and magnitude of effects of genes that cause variation in longevity using DNA-based genetic markers. 2) Demography of Genes- We will estimate age-dependent mortality parameters for small chromosomal segments carried in genetically homogeneous recombinant inbred lines. 3) ADL Experiments- We will characterize age-dependent disability in cohorts of genetically homogeneous flies, and estimate the genetic correlation of mortality and morbidity across genotypes. Notable features are: (i) The experiments emphasize large scale data collection for estimation of genetic and demographic parameters. (ii) QTL mapping experiments employ some of the most recent developments in DNA technology (PCR and RAPDs). (iii) Data will be informative about the genetic basic of male-female correlations. (iv) Data will be archive for general access. Health relevance: The research will provide information about the plasticity of morbidity and mortality at the oldest ages in a model experimental system.

This project focuses on identifying and characterizing genes that extend life span (LAG's) in Drosophila melanogaster. The main tool is a set of 120 recombinant inbred (R1) lines derived from artificially selected long-lived and control stocks. Specific aims are (1) To test the hypothesis that LAG's pleiotropically affect other characters, including fertility and metabolic rate; (2) To execute fine-scale mapping and characterization of four QTL's identified on chromosomes 2 and 3, using single-nucleotide polymorphisms (SNPs); (3) To screen for point mutations and P-factor insertions that specifically after survival at the oldest ages; (4) To develop stocks for future research, including new RI's and lines that can reliably recover from freezing. Notable features of the proposed experiments are: (1) RI's derived from long-lived stocks are a unique and unusually valuable resource that took 4 years to construct; (2) The proposed research is a collaborative effort involving labs at 4 universities, (3) Experiments will be done on a large scale; the PI's lab routinely executes survival experiments with 100,000 flies; (4) It is important to study the RI's as soon as possible, because large sets of inbred lines tend to degenerate over time, due to the accumulation of new mutations and rare contamination; (5) Development of freeze-resistant flies is a high risk project that has the potential to revolutionize Drosophila research. Health relevance: It is important to test the pleiotropy hypotheses because they imply that interventions to extend life span my have deleterious effects early in life.

Abstract: DESCRIPTION: (adapted from the application): This project proposes to examine the relationships between longevity, nutrition, and reproduction in the Medkerranean fruit fly. It will be framed around the recent finding that the life history of female medflies can be characterized by two physiological modes with different demographic schedules of fertility and survival: (I) a waiting mode in which both mortality and reproduction are low; and (ii) a reproductive mode in which mortality is very low at the onset of egg laying but accelerates as eggs are laid. The project will involve Drs. James Carey (UC Davis), Lawrence Harshman (University of Nebraska) and Linda Partridge (University College London) with data gathered at the Moscamed mass rearing facility in Tapachula, Mexico under the direction of Dr. Pablo Liedo. Professors Hans Muller and Jane-Ling Wang (Division of Statistics, UC Davis) will assist with data management and statistical analyses. The specific aims are to test the following hypotheses: (1) The interplay of aging modes will have fundamentally different effects on the life history characteristics of females: a. Females will live longer when they experience both modes of aging than if they experience one exclusively. b. females will lay more eggs in their lifetimes when they experience only the reproductive mode with continuous feeding on a full diet. c. The local characteristics of the mortality trajectory such as the timing of the mortality "shoulder" or the peak will shift when females experience both modes of aging; (2) The effects of dietary restriction on longevity are mediated through reductions in reproductive rates and costs; (3) The genes and mechanisms elevating longevity in waiting and reproductive mode are different, and possibly mutually exclusive; and (4) the effects of nutrition and reproduction on survival rates are mediated through changes in numbers of active ovadoles, modulations of yolk protein synthesis, and changes in hormone titers.