Our goal is to use theoretical models, gene expression arrays, molecular genetic markers (SNPs and microsatellites) and molecular evolutionary theory to better understand how gene interactions (epistasis) produce complex phenotypes. As our experimental system, we will use recently collected populations of the red flour beetle, Tribolium castaneum, which exhibit characteristics of incipient speciation in the form of inter-population hybrids with impaired behavior, morphological deformities, and reduced fertility and viability.
Our specific aims i nclude (1) confirming the functional identity of a pair of genes from different populations that cause a total reduction of hybrid fitness when brought together in a common genetic background;(2) characterizing the molecular evolution of these genes through their patterns of expression and sequence diversity within and among species;(3) identifying, confirming and characterizing a different set of interacting genes which impair the motor behavior of inter-population hybrids;(4) characterizing the differences in gene expression between inter-population hybrids and their parents using Nimblegen(c) microarrays;and, (5) extending and testing two-locus population genetic theory to a new model of speciation based on interactions between a pair of genes, one with maternal and one with zygotic expression. Our extensive preliminary studies, crossing pairs of populations from North and South America, Africa and Asia, have revealed that dominance, epistasis, maternal genetic effects, and genotype-by-environment interaction cause morphological and behavioral abnormalities and reduced viability and fertility in inter-population hybrids. For the most extreme case of hybrid fitness reduction, we have shown, through repeated back-crossing to the genome strain, GA-2, and microsatellite marker mapping, that a specific pair of genes interacts to reduce hybrid fitness. We have also shown that inter-population behavioral abnormalities occur in matings and backcrosses between a different pair of populations; that they are not caused one of the genes responsible for the extreme reduction of hybrid fitness (above);and that they involve the breakdown of linked gene combinations. By continuing our back-crosses to the genomic strain, we can isolate the gene combinations causing the behavioral abnormalities in a common genetic background, confirm their functional identity, and characterize their evolution within and among species.

Public Health Relevance

Gene interactions (epistasis) play a central role in speciation in particular. Deleterious gene combinations in hybrids produce negative phenotypes like deformities, reduced fertility, and reduced viability, which are similar to those of complex human genetic diseases, like diabetes, autism, obesity, and schizophrenia. Although single genes involved in reproductive isolation between species have been identified, the gene combinations and their specific causal interactions are not known.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Eckstrand, Irene A
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Indiana University Bloomington
Schools of Arts and Sciences
United States
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Wade, Michael J (2013) Phase III of Wright's shifting balance process and the variance among demes in migration rate. Evolution 67:1591-7
Watson, Eric T; Demuth, Jeffery P (2012) Haldane's rule in marsupials: what happens when both sexes are functionally hemizygous? J Hered 103:453-8
Demuth, Jeffery P; Naidu, Amrita; Mydlarz, Laura D (2012) Sex, war, and disease: the role of parasite infection on weapon development and mating success in a horned beetle (Gnatocerus cornutus). PLoS One 7:e28690
Drury, D W; Wade, M J (2011) Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum. J Evol Biol 24:168-76
Yu, Q; Ellen, E D; Wade, M J et al. (2011) Genetic differences among populations in sexual dimorphism: evidence for selection on males in a dioecious plant. J Evol Biol 24:1120-7
Prince, Eldon G; Kirkland, Donna; Demuth, Jeffery P (2010) Hyperexpression of the X chromosome in both sexes results in extensive female bias of X-linked genes in the flour beetle. Genome Biol Evol 2:336-46
Priest, Nicholas K; Wade, Michael J (2010) Maternal-zygotic epistasis and the evolution of genetic diseases. J Biomed Biotechnol 2010:478732
Van Dyken, J David; Wade, Michael J (2010) The genetic signature of conditional expression. Genetics 184:557-70
Drury, Douglas W; Siniard, Ashley L; Wade, Michael J (2009) Genetic differentiation among wild populations of Tribolium castaneum estimated using microsatellite markers. J Hered 100:732-41
Brandvain, Yaniv; Wade, Michael J (2007) The evolution of competition and policing: opposing selection within and among groups. BMC Evol Biol 7:203

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