Johnny Cruz Corchado and Joshua Fletcher will Present their Research on Thursday, 6/11/15
Consequences of Recombination rate variation among Drosophila Melanogaster populations
Recombination is a crucial biological process that shapes evolutionary change within and between species. At the same time, accurate estimates of recombination rates are essential for correct inferences of selection and demographic events. In this study, we use the most accurate population genetic method, LDhelmet, to estimate and compare recombination rates in three Drosophila melanogaster populations. Recombination rates not only change in total magnitude but also in their relative distribution within chromosomes (landscapes). We show that differences in recombination landscapes between populations do not accumulate at the same rate than nucleotide differences. We also show that population-specific differences in recombination landscapes play a significant role explaining population-specific differences in nucleotide diversity. Our results suggest that inter-population differences in local recombination rates and the corresponding differences in local Background Selection (BGS) need to be considered as a possible explanation for population-specific differences in nucleotide diversity at specific genomic regions.
A NATURALLY OCCURRING MUTATION IN THE FERROUS IRON UPTAKE GENE FEOB CONFERS ENHANCED RESISTANCE TO OXIDATIVE STRESS IN A FRANCISELLA TULARENSIS VACCINE STRAIN
J Fletcher1, C Bosio2, B Jones1,3
1 The Interdisciplinary Graduate Program in Genetics, University of Iowa
2 Laboratory of Intracellular Parasites, Rocky Mountain Labs, National Institute of Allergy and Infectious Diseases Department of Microbiology, Carver College of Medicine, University of Iowa
3 Department of Microbiology, Carver College of Medicine, University of Iowa
Francisella tularensis is a highly virulent bacterial pathogen with an extremely low infectious dose (~10 CFU) and high rates of mortality if left untreated (30-60%). F. tularensis has an extensive history as a bioweapon, and there is no vaccine currently licensed. For these reasons the CDC considers F. tularensis a Tier 1 Select Agent. The unlicensed Live Vaccine Strain (LVS) provides moderate protection against virulent strains; however, we have recently discovered that various lab stocks differ in their virulence and ability to confer immunity. Genome sequencing of high virulence (RML, LD50 ~200 CFU) and low virulence (ATCC, LD50 ~9,000 CFU) strains has identified nine differences, of which four are non-synonymous substitutions. One such mutation occurs in the ferrous iron uptake gene feoB in RML. While iron is required for cellular function, ferrous iron can participate in the Fenton reaction with H2O2, leading to inactivation of essential iron-sulfur cluster enzymes, and DNA damage. Part of the innate immune response involves the oxidative burst in the phagosome and mitochondria-derived ROS in the cytosol. Fully virulent strains of F. tularensis are known to be highly resistant to such host defences, and have low levels of intracellular iron. Accordingly, the RML strain was highly resistant to exogenous H2O2 in vitro relative to the ATCC strain. Overexpression of the ATCC feoB allele, but not the RML allele, leads to significantly increased sensitivity to H2O2. Furthermore, the RML strain grows poorly under conditions of iron starvation, and an iron-responsive lacZ reporter had ~3-fold higher activity in the RML strain relative to ATCC under these conditions. Overexpression of the iron-responsive transcriptional repressor fur leads to reduced growth in the RML strain, but not ATCC. These results are consistent with the hypothesis that RML has less intracellular iron, and that this may lead to increased resistance to host-mediated oxidative stress.