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Image by Alison Larsen

This research investigates the genetic variation in susceptibility to the bacterial pathogen Pseudomonas aeruginosa in the nematode Caenorhabditis elegans. By analyzing mutational variance and the effects of polygenic traits, we explore how genetic factors contribute to differing responses to pathogen exposure. Our findings show that susceptibility is a quantitative trait influenced by mutations under stabilizing selection. This study provides insights into the complex genetic architecture behind pathogen resistance, contributing to our understanding of evolutionary biology and genetics in model organisms.

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Image by Alison Larsen

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  1. The Red Death Meets the Abdominal Bristle: Polygenic Mutation for Susceptibility to a Bacterial Pathogen in Caenorhabditiselegans Veronique Etienne1, Erik C. Andersen2, Jose Miguel Ponciano1, and Charles F. Baer1 1- Dept. of Biology, University of Florida, Gainesville, FL 2- Dept. of Molecular Biosciences, Northwestern University, Evanston, IL Image by Alison Larsen

  2. Question (Age-old): • When “something is going around”, why do some individuals become deathly ill, other individuals only get mildly sick and other individuals don’t get sick at all?

  3. Question (Age-old): • When “something is going around”, why do some individuals become deathly ill, other individuals only get mildly sick and other individuals don’t get sick at all? • That is, what are the sources of variation in the response to exposure to pathogens?

  4. Point of departure: • Variation in the response to pathogen(s) often has a genetic basis • In some cases one or a few loci of large effect underlie variation (e.g., β-globin/sickle cell/malaria) • In other cases the variation appears to be polygenic

  5. Quantitative Genetics of Pathogen Susceptibility in C. elegans • How much genetic variance is introduced by mutation? • VM = UQα2 • VM = per-generation increase in genetic variance due to new mutations (“mutational variance”) • U = genome-wide mutation rate • Q = fraction of genome that can affect the trait (“mutational target”) • α= average effect of a mutation on the trait

  6. The Mutation Accumulation (MA) Process N=1 N=1 N=1

  7. Evolution under MA conditions 1 Fitness Genetic Variance (slope=VM) 0 0 Generations of MA

  8. Evolution under MA conditions: Mutational Bias (ΔM) Trait Y (e.g., time to maturity) 1 Trait X (e.g., size at maturity) Fitness 0 0 Generations of MA

  9. The Phenotype: Susceptibility of C. elegansto the pathogenic effects of Pseudomonas aeruginosa • Inoculate a 35 mm plate w/ 5 ul of saturated P. aeruginosa (PA14) • Introduce ~30 L4-stage juvenile C. elegans • Record mortality at 12 hr intervals for 128 hrs • Median time of death (LT50) is the measure of susceptibility to the pathogen

  10. Results (1): Mutational Variance, compared with other traits measured in these C. elegansMA lines

  11. Results (2): LT50Pa vs. the Dmel Bristle

  12. Results (3): Mutational Heritability (VM/VE), compared with other traits in C. elegans

  13. Results (4): Mutational Bias (ΔM)

  14. Results (5): Selection Gradient – LT50Pa is under asymmetric stabilizing selection

  15. 4NeVM Neutral Trait s=.001 s=.01 s=.1 s=1 Dominant Lethal

  16. Results (6): Comparison with standing genetic variation; at MSB, VM/VG ~ s VG x 105 VM x 105

  17. Results (7): Distribution of Mutational Effects: Large Target (Q≥0.5%), Modest Effects (|α|~ “a few percent”)

  18. Conclusions: • Susceptibility to this pathogen (the PA14 strain of P. aeruginosa) of this host (the PB306 strain of C. elegans) as quantified in this way (LT50) is a typical quantitative trait • Mutations that affect susceptibility to P. aeruginosaare under asymmetric stabilizing selection of a few tenths of a percent. • A model of large target/small-to-modest effects fits the data better than a model with a small mutational target and large effects.

  19. Thanks! • NIH R01GM072639 (CFB) • Ruth Kirschstein NRSA F32-GM089007 (ECA) • NCI Training Grant T32-CA009528 (ECA) • Joanna Chan • Sarah Eaton • Nick Martinez • Andy Mills • Joanna Tran-Nguyen • Matt Vasquez Postdoc Wanted!

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