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Medea selfish genetic elements as tools for altering traits of wild populations : a theoretical analysis

Citation

Ward, Catherine Marie (2011) Medea selfish genetic elements as tools for altering traits of wild populations : a theoretical analysis. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:05312011-123357339

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Abstract

Insect-borne diseases kill millions of people annually. One strategy for controlling transmission of insect-borne disease involves replacing the native insect population with transgenic animals unable to transmit disease. Population replacement requires a drive mechanism to ensure the rapid spread of linked transgenes conferring disease refractoriness. Medea selfish genetic elements have the feature that when present in a female, only offspring that inherit the element survive, a behavior that can lead to spread. Here we use modeling to identify conditions under which Medea elements spread. We derive equations describing the allele frequencies required for spread of Medea elements with a fitness cost, and the equilibrium allele frequencies attained. We validate our model against a synthetic Medea element created in Drosophila and find that the model fits the data without parameter fitting. We show that when Medea spreads, it drives the non-Medea genotype out of the population, and we provide estimates of the number of generations required to achieve this goal. We also characterize two contexts in which Medea elements with fitness costs drive the non-Medea allele from the population: an autosomal element in which zygotic rescue is incomplete and an X-linked element in species in which X/Y individuals are male. Finally, we explore costs and benefits associated with the introduction of multiple Medea elements. Our results suggest that Medea elements can drive population replacement under a wide range of conditions, potentially reducing disease burden.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:selfish genetic element, Medea, mosquito, malaria
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Hay, Bruce
Thesis Committee:
  • Sternberg, Paul W. (chair)
  • Elowitz, Michael B.
  • Murray, Richard M.
  • Hay, Bruce A.
Defense Date:20 December 2010
Author Email:ward.catherine (AT) gmail.com
Funders:
Funding AgencyGrant Number
NIHGM057422
NIHGM70956
NIHR01 GM072879
NIHR01 GM070956
NIHDP1 OD003878
Regents of the University of California from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiativeUNSPECIFIED
Record Number:CaltechTHESIS:05312011-123357339
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05312011-123357339
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6480
Collection:CaltechTHESIS
Deposited By: Catherine Ward
Deposited On:31 May 2011 23:11
Last Modified:26 Dec 2012 04:36

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