Browsing by Author "Leips, Jeff"
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Item ADAPTIVE MATERNAL ADJUSTMENTS OF OFFSPRING SIZE IN RESPONSE TO CONSPECIFIC DENSITY IN TWO POPULATIONS OF THE LEAST KILLIFISH, HETERANDRIA FORMOSA(Oxford University Press, 2009-05-01) Leips, Jeff; Richardson, Jean M. L.; Rodd, F. Helen; Travis, JosephGiven a trade-off between offspring size and number and an advantage to large size in competition, theory predicts that the offspring size that maximizes maternal fitness will vary with the level of competition that offspring experience. Where the strength of competition varies, selection should favor females that can adjust their offspring size to match the offspring's expected competitive environment. We looked for such phenotypically plastic maternal effects in the least killifish, Heterandria formosa, a livebearing, matrotrophic species. Long-term field observations on this species have revealed that some populations experience relatively constant, low densities, whereas other populations experience more variable, higher densities. We compared sizes of offspring born to females exposed during brood development to either low or high experimental densities, keeping the per capita food ration constant. We examined plastic responses to density for females from one population that experiences high and variable densities and another that experiences low and less-variable densities. We found that, as predicted, female H. formosa produced larger offspring at the higher density. Unexpectedly, we found similar patterns of plasticity in response to density for females from both populations, suggesting that this response is evolutionarily conserved in this species.Item The adaptive significance of population differentiation in offspring size of the least killifish, Heterandria formosa(Wiley, 2013-03-05) Leips, Jeff; Rodd, F. Helen; Travis, JosephWe tested the hypothesis that density-dependent competition influences the evolution of offspring size. We studied two populations of the least killifish (Heterandria formosa) that differ dramatically in population density; these populations are genetically differentiated for offspring size, and females from both populations produce larger offspring when they experience higher social densities. To look at the influences of population of origin and relative body size on competitive ability, we held females from the high-density population at two different densities to create large and small offspring with the same genetic background. We measured the competitive ability of those offspring in mesocosms that contained either pure or mixed population treatments at either high or low density. High density increased competition, which was most evident in greatly reduced individual growth rates. Larger offspring from the high-density population significantly delayed the onset of maturity of fish from the low-density population. From our results, we infer that competitive conditions in nature have contributed to the evolution of genetically based interpopulation differences in offspring size as well as plasticity in offspring size in response to conspecific density.Item Age Specificity of Inbreeding Load in Drosophila melanogaster and Implications For the Evolution of Late-Life Mortality Plateaus(Oxford University Press, 2007-09-01) Reynolds, Rose M; Temiyasathit, Sara; Reedy, Melissa M; Ruedi, Elizabeth A; Drnevich, Jenny M; Leips, Jeff; Hughes, Kimberly ACurrent evolutionary theories explain the origin of aging as a byproduct of the decline in the force of natural selection with age. These theories seem inconsistent with the well-documented occurrence of late-life mortality plateaus, since under traditional evolutionary models mortality rates should increase monotonically after sexual maturity. However, the equilibrium frequencies of deleterious alleles affecting late life are lower than predicted under traditional models, and thus evolutionary models can accommodate mortality plateaus if deleterious alleles are allowed to have effects spanning a range of neighboring age classes. Here we test the degree of age specificity of segregating alleles affecting fitness in Drosophila melanogaster. We assessed age specificity by measuring the homozygous fitness effects of segregating alleles across the adult life span and calculated genetic correlations of these effects across age classes. For both males and females, we found that allelic effects are age specific with effects extending over 1–2 weeks across all age classes, consistent with modified mutation-accumulation theory. These results indicate that a modified mutation-accumulation theory can both explain the origin of senescence and predict late-life mortality plateaus.Item Age-Specific Variation in Immune Response in Drosophila melanogaster Has a Genetic Basis(Oxford University Press, 2012-07-01) Felix, Tashauna M; Hughes, Kimberly A; Stone, Eric A; Drnevich, Jenny M; Leips, JeffImmunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know little about the genetic influences on this phenomenon. In this study we combined age-specific measurements of bacterial clearance ability following infection with whole-genome measurements of the transcriptional response to infection and wounding to identify genes that contribute to the natural variation in immunosenescence, using Drosophila melanogaster as a model system. Twenty inbred lines derived from nature were measured for their ability to clear an Escherichia coli infection at 1 and 4 weeks of age. We used microarrays to simultaneously determine genome-wide expression profiles in infected and wounded flies at each age for 12 of these lines. Lines exhibited significant genetically based variation in bacterial clearance at both ages; however, the genetic basis of this variation changed dramatically with age. Variation in gene expression was significantly correlated with bacterial clearance ability only in the older age group. At 4 weeks of age variation in the expression of 247 genes following infection was associated with genetic variation in bacterial clearance. Functional annotation analyses implicate genes involved in energy metabolism including those in the insulin signaling/TOR pathway as having significant associations with bacterial clearance in older individuals. Given the evolutionary conservation of the genes involved in energy metabolism, our results could have important implications for understanding immunosenescence in other organisms, including humans.Item Ancestral ecological regime shapes reaction to food limitation in the Least Killifish, Heterandria formosa(Wiley Online Library, 2012-04-06) Felmy, Anja; Leips, Jeff; Travis, JosephPopulations with different densities often show genetically based differences in life histories. The divergent life histories could be driven by several agents of selection, one of which is variation in per-capita food levels. Its relationship with population density is complex, as it depends on overall food availability, individual metabolic demand, and food-independent factors potentially affecting density, such as predation intensity. Here, we present a case study of two populations of a small live-bearing freshwater fish, one characterized by high density, low predation risk, low overall food availability, and presumably low per-capita food levels, and the other by low density, high predation risk, high overall food availability, and presumably high per-capita food levels. Using a laboratory experiment, we examined whether fish from these populations respond differently to food limitation, and whether size at birth, a key trait with respect to density variation in this species, is associated with any such differential responses. While at the lower food level growth was slower, body size smaller, maturation delayed, and survival reduced in both populations, these fitness costs were smaller in fish from the high-density population. At low food, only 15% of high-density fish died, compared to 75% of low-density fish. This difference was much smaller at high food (0% vs. 15% mortality). The increased survival of high-density fish may, at least partly, be due to their larger size at birth. Moreover, being larger at birth enabled fish to mature relatively early even at the lower food level. We demonstrate that sensitivities to food limitation differ between study populations, consistent with selection for a greater ability to tolerate low per-capita food availability in the high-density population. While we cannot preclude other agents of selection from operating in these populations simultaneously, our results suggest that variation in per-capita food levels is one of those agents.Item The Anderson Agenda Ep 004 – Why Don’t Dogs Live That Long? (w/ Jeff Leips)(98Rock, 2017-08-11) Anderson, Mike; Leips, JeffItem Assessing the Age-Specific Phagocytic Ability of Adult Drosophila melanogaster Hemocytes using an In Vivo Phagocytosis Assay(JOVE, 2020-06-11) Campbell, Shonda M.; Starz-Gaiano, Michelle; Leips, JeffPhagocytosis is an essential function of the innate immune response. This process is carried out by phagocytic hemocytes whose primary function is to recognize a wide range of particles and destroy microbial pathogens. As organisms age, this process begins to decline, yet little is known about the underlying mechanisms or the genetic basis of immunosenescence. Here, an injection based in vivo phagocytosis assay is used to assess age related changes in different aspects of phagocytosis, such as binding, engulfment, and degradation of internalized particles, by quantifying phagocytic events in hemocytes in adult Drosophila. Drosophila melanogaster has become an ideal model to investigate age related changes in innate immune function for many reasons. For one, many genetic components and functions of the innate immune response, including phagocytosis, are evolutionarily conserved between Drosophila and mammals. Because of that, results obtained from using this protocol are likely to be widely relevant to understanding the age related changes in immune function in a variety of organisms. Additionally, we note that this method provides quantitative estimates of hemocyte phagocytic ability, which could be useful for a variety of research topics, and need not be limited to studies of aging.Item The comparative expression of life-history traits and its relationship to the numerical dynamics of four populations of the least killifish(Wiley, 2001-12-25) Leips, Jeff; Travis, Joseph1. We examined the numerical dynamics in four natural populations of the least killifish [Heterandria formosaAgassiz (1855)]; to ascertain how those dynamics affected the expression of key life-history traits and, in turn, whether life-history variation among populations might be responsible for different dynamic properties. Populations were chosen from two types of communities, spring-fed rivers and lakes, to examine the relative influence of community characteristics on these relationships. 2. Populations in lakes had lower densities, more female-biased sex ratios and a smaller proportion of immature individuals than populations in rivers. Predator faunas differed between habitats and the ratio of predator to H. formosa density was higher in lakes than in rivers. 3. Females in lake populations were 35−40% larger than river females. Female size was positively correlated with the number of broods carried by a female at any given time and the number of offspring in a particular brood. These correlations and the larger body size of females in lake populations indicate that the reproductive output per female was higher in lake than river populations. 4. Female size was negatively correlated with population density in two of the four populations. After adjusting for the variation in female size, brood size and brood numbers were negatively correlated with population density in only the highest density population. 5. Average offspring size was negatively correlated with brood size in all of the populations, indicating a general trade-off between offspring size and number. The average offspring size in the highest density population was as much as 45% larger than that of all other populations, an effect independent of any phenotypic plasticity in offspring size with respect to female body size or density. 6. The effects of density on female body size are the major avenue for negative feedback of population density on the subsequent dynamics through life-history expression. Whether such an effect is stabilizing or destabilizing cannot yet be determined. If the variation in offspring size among populations is adaptive, it may be a prominent example of density-dependent life-history evolution.Item A comparison of feeding rate methods in Drosophila melanogaster indicates that consumption is influenced by body size(The University of Oklahoma, 2016) Daya, Payal D.; Leips, Jeff; Durham, MaryDietary restriction, a decrease in nutrient intake without malnutrition, has been shown to increase life span in many species and is highly linked to feeding behavior. Although Drosophila melanogaster is an excellent model organism to study the effects of dietary restriction on life span and associated traits, measuring feeding rate in this organism is particularly challenging. Several methods have been used to estimate feeding rate in Drosophila melanogaster, but it remains unclear which method is most precise. We examined the effectiveness of two popular methods that label media with blue dye or radioactive isotopes to quantify food uptake. We found that the radioactive label assay was more precise than the blue dye assay and likely most useful for comparing the effects of different treatments (genotypes, diets) on feeding rates. We found that the relationship between feeding rate and dietary treatment depends on the size of the fly, so we also suggest incorporating body size as a covariate in data analysis to improve the accuracy of feeding rate estimates.Item A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism(Plos One, 2010-06-23) Luca, Maria De; Klimentidis, Yann C.; Casazza, Krista; Chambers, Michelle Moses; Cho, Ruth; Harbison, Susan T.; Jumbo-Lucioni, Patricia; Zhang, Shaoyan; Leips, Jeff; Fernandez, Jose R.Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism.Item DEFENSE TRAITS OF LARVAL DROSOPHILA MELANOGASTER EXHIBIT GENETICALLY BASED TRADE-OFFS AGAINST DIFFERENT SPECIES OF PARASITOIDS(Oxford University Press, 2013-03-01) Hodges, Theresa K.; Laskowski, Kate L.; Squadrito, Giuseppe L.; Luca, Maria De; Leips, JeffPopulations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species-specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade-offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade-off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade-off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits.Item Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses(The American Society for Cell Biology, 2017-10-13) Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, JeffRedesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory biology courses. Modules are designed to improve skills in quantitative numeracy, interpreting data sets using visual tools, and making inferences about biological phenomena using mathematical/statistical models. We also examine demographic/background data that predict student improvement in these skills through exposure to these modules. We carried out pre/postassessment tests across four semesters and used student interviews in one semester to examine how students at different levels approached quantitative problems. We found that students improved in all skills in most semesters, although there was variation in the degree of improvement among skills from semester to semester. One demographic variable, transfer status, stood out as a major predictor of the degree to which students improved (transfer students achieved much lower gains every semester, despite the fact that pretest scores in each focus area were similar between transfer and nontransfer students). We propose that increased exposure to quantitative skill development in biology courses is effective at building competency in quantitative reasoning.Item DROP: Molecular voucher database for identification of Drosophila parasitoids(Wiley, 2021-05-29) Lue, Chia-Hua; Buffington, Matthew L.; Scheffer, Sonja; Lewis, Matthew; Leips, Jeff; et alMolecular identification is increasingly used to speed up biodiversity surveys and laboratory experiments. However, many groups of organisms cannot be reliably identified using standard databases such as GenBank or BOLD due to lack of sequenced voucher specimens identified by experts. Sometimes a large number of sequences are available, but with too many errors to allow identification. Here, we address this problem for parasitoids of Drosophila by introducing a curated open-access molecular reference database, DROP (Drosophila parasitoids). Identifying Drosophila parasitoids is challenging and poses a major impediment to realize the full potential of this model system in studies ranging from molecular mechanisms to food webs, and in biological control of Drosophila suzukii. In DROP, genetic data are linked to voucher specimens and, where possible, the voucher specimens are identified by taxonomists and vetted through direct comparison with primary type material. To initiate DROP, we curated 154 laboratory strains, 856 vouchers, 554 DNA sequences, 16 genomes, 14 transcriptomes, and six proteomes drawn from a total of 183 operational taxonomic units (OTUs): 114 described Drosophila parasitoid species and 69 provisional species. We found species richness of Drosophila parasitoids to be heavily underestimated and provide an updated taxonomic catalogue for the community. DROP offers accurate molecular identification and improves cross-referencing between individual studies that we hope will catalyse research on this diverse and fascinating model system. Our effort should also serve as an example for researchers facing similar molecular identification problems in other groups of organisms.Item The Edge Effect(QUBES, 2023-05-03) McNamara, Sean; Newtoff, Kiersten; Livernoche, Kelly; Bell, Allison; Leips, Jeff; Wesley, Gina; Gretes, WilliamThis module has students venturing outdoors to take a 50m transect and collect abundance data on plants utilizing quadrats in both edge and interior environment. Mathematically the goals of this module are to emphasize how sample size can influence data analysis and variance within the data set. Students perform calculations for species diversity using the Shannon-Wiener Diversity Index. They will then take averages and the standard error of their data set, and use this information to create a graph. They will repeat this process for the entire class data set. Students will also run the student’s t-test to test for significance between the two environments.Item Evolution in Population Parameters: Density-Dependent Selection or Density-Dependent Fitness?(University of Chicago Press, 2013-05) Travis, Joseph; Leips, Jeff; Rodd, F. HelenDensity-dependent selection is one of earliest topics of joint interest to both ecologists and evolutionary biologists and thus occupies an important position in the histories of these disciplines. This joint interest is driven by the fact that density-dependent selection is the simplest form of feedback between an ecological effect of an organism’s own making (crowding due to sustained population growth) and the selective response to the resulting conditions. This makes density-dependent selection perhaps the simplest process through which we see the full reciprocity between ecology and evolution. In this article, we begin by tracing the history of studying the reciprocity between ecology and evolution, which we see as combining the questions of evolutionary ecology with the assumptions and approaches of ecological genetics. In particular, density-dependent fitness and density-dependent selection were critical concepts underlying ideas about adaptation to biotic selection pressures and the coadaptation of interacting species. However, theory points to a critical distinction between density-dependent fitness and density-dependent selection in their influences on complex evolutionary and ecological interactions among coexisting species. Although density-dependent fitness is manifestly evident in empirical studies, evidence of density-dependent selection is much less common. This leads to the larger question of how prevalent and important density-dependent selection might really be. Life-history variation in the least killifish Heterandria formosa appears to reflect the action of density-dependent selection, and yet compelling evidence is elusive, even in this well-studied system, which suggests some important challenges for understanding density-driven feedbacks between ecology and evolution.Item Genes Contributing to Resilience and Sensitivity to Lisinopril at Old Age: Clinical Translation of GWA in Drosophila(Oxford University Press, 2021-12-17) Gabrawy, Mariann M; Khosravian, Nick; Morcos, George S; Jezek, Meagan; Walston, Jeremy; Abadir, Peter M; Leips, JeffDespite impressive results in restoring physical performance in rodent models, treatment with Renin-Angiotensin System (RAS) inhibitors such as Lisinopril have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs such as RAS inhibitors remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila, we tested the effects of Lisinopril on climbing speed and endurance at young and old age (N=14,310). Our data show that functional response and sensitivity to Lisinopril ranges from significant protection against physical decline (8–100% faster, P< 0.0001) to increased weakness (P< 0.0001) depending on both genotype and age (P< 0.0001). Genome-wide analyses revealed little to no overlap in candidate polymorphisms influencing sensitivity between ages nor between treatments within each age. Furthermore, network analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in sensitivity to Lisinopril. Genetic knockdown of Axin, frizzled, nemo, and wingless, genes with human orthologs AXIN1, FZD1, NLK, and WNT1, respectively, abolished the effects of Lisinopril treatment. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and as potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age-dependent responses to pharmaceutical treatments.Item Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits(Nature, 2014-07-08) Durham, Mary; Magwire, Michael M.; Stone , Eric A.; Leips, JeffMost organisms exhibit senescence; a decline in physiological function with age. In nature, rates of senescence vary extensively among individuals and this variation has a significant genetic component; however, we know little about the genes underlying senescence. Here we show the first evidence that individual alleles influence fecundity in an age-specific manner and so the genetic basis of natural variation in fecundity changes dramatically with age. We complete a genome-wide association to identify single-nucleotide polymorphisms (SNPs) affecting lifespan and age-specific fecundity using the Drosophila melanogaster Genetic Reference Panel. We identify 1,031 SNPs affecting fecundity and 52 influencing lifespan. Only one SNP is associated with both early- and late-age fecundity. The age-specific effect of candidate genes on fecundity is validated using RNA interference. In addition, there is a dramatic increase in the number of SNPs influencing fecundity with age. This result provides support for the mutation accumulation theory of aging.Item Genome-Wide Analysis in Drosophila Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition(MDPI, 2022-01-14) Gabrawy, Mariann M.; Khosravian, Nick; Morcos, George S.; Morozova, Tatiana V.; Jezek, Meagan; Walston, Jeremy D.; Huang, Wen; Abadir, Peter M.; Leips, JeffDespite impressive results in restoring physical performance in rodent models, treatment with renin–angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila melanogaster, we tested the effects of Lisinopril on age-specific climbing speed and endurance. Our data show that functional response and sensitivity to Lisinopril treatment ranges from significant protection against physical decline to increased weakness depending on genotype and age. Furthermore, genome-wide analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in physical performance traits and sensitivity to Lisinopril treatment. Genetic knockdown of genes in the WNT signaling pathway, Axin, frizzled, nemo, and wingless, diminished or abolished the effects of Lisinopril treatment on climbing speed traits. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and because they have orthologs in humans, they are potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age- and sex-dependent responses to any type of pharmaceutical treatment.Item Genome-wide association study identifies genes and networks that influence innate immune response in an age-specific manner in Drosophila melanogaster(2022-12-09) Campbell, Shonda; Gudino, Isabella; Rhee, Mary; Leips, JeffBackground The innate immune response is an evolutionarily conserved process that is essential for survival in multicellular organisms. As individuals age, immune functions decline, a phenomenon known as immunosenescence, reducing one’s ability to fight infections. While immunosenescence is a universal feature of aging, the rate at which immune functions decline with age varies greatly among individuals and this variation has a genetic component. However, we have limited knowledge of the actual genes that contribute to this variation. Methods Here, we used 183 genetically distinct genotypes of the Drosophila Genetic Reference panel (DGRP) to assess their ability to clear an infection at one and five weeks of age. We then carried out a genome-wide association study (GWAS) to identify candidate genes that contribute to differences in immune responses among genotypes at each age. Results We found that, on average, the ability to clear infection declined by 70% with age. However, the effect of age on clearance ability varied significantly among genotypes. We identified a total of 242 single nucleotide polymorphisms (SNPs) and 107 candidate genes associated with variation in clearance ability. Polymorphisms in 48 genes were associated with clearance in 1 week old flies and fifty-nine genes were associated with clearance ability at 5 weeks of age. Only one gene, a G-coupled protein receptor, CG31760, was a candidate at both ages. Of the 107 candidate genes, 25 were mapped to genetic networks. Conclusion Our results identify candidate genes that could be targets for age-appropriate therapeutic treatments to maintain or restore immune function in the elderly.Item GENOMIC BASIS OF AGING AND LIFE-HISTORY EVOLUTION IN DROSOPHILA MELANOGASTER(Oxford University Press, 2012-11-01) Remolina, Silvia C.; Chang, Peter L.; Leips, Jeff; Nuzhdin, Sergey V.; Hughes, Kimberly A.Natural diversity in aging and other life-history patterns is a hallmark of organismal variation. Related species, populations, and individuals within populations show genetically based variation in life span and other aspects of age-related performance. Population differences are especially informative because these differences can be large relative to within-population variation and because they occur in organisms with otherwise similar genomes. We used experimental evolution to produce populations divergent for life span and late-age fertility and then used deep genome sequencing to detect sequence variants with nucleotide-level resolution. Several genes and genome regions showed strong signatures of selection, and the same regions were implicated in independent comparisons, suggesting that the same alleles were selected in replicate lines. Genes related to oogenesis, immunity, and protein degradation were implicated as important modifiers of late-life performance. Expression profiling and functional annotation narrowed the list of strong candidate genes to 38, most of which are novel candidates for regulating aging. Life span and early age fecundity were negatively correlated among populations; therefore, the alleles we identified also are candidate regulators of a major life-history trade-off. More generally, we argue that hitchhiking mapping can be a powerful tool for uncovering the molecular bases of quantitative genetic variation.
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