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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM065414-08
Application #
8235919
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2003-05-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
8
Fiscal Year
2012
Total Cost
$428,234
Indirect Cost
$92,074
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Wolf, Jason B; Wade, Michael J (2016) Evolutionary genetics of maternal effects. Evolution 70:827-39
Drury, Douglas W; Whitesell, Matthew E; Wade, Michael J (2016) The effects of temperature, relative humidity, light, and resource quality on flight initiation in the red flour beetle, Tribolium castaneum. Entomol Exp Appl 158:269-274
Moorad, Jacob A; Wade, Michael J (2013) Selection gradients, the opportunity for selection, and the coefficient of determination. Am Nat 181:291-300
Wade, Michael J (2013) Phase III of Wright's shifting balance process and the variance among demes in migration rate. Evolution 67:1591-7
Williford, Anna; Demuth, Jeffery P (2012) Gene expression levels are correlated with synonymous codon usage, amino acid composition, and gene architecture in the red flour beetle, Tribolium castaneum. Mol Biol Evol 29:3755-66
Cruickshank, Tami; Wade, Michael J (2012) Maternal adjustment of the sex ratio in broods of the broad-horned flour beetle, Gnathocerus cornutus. Integr Comp Biol 52:100-7
Drown, Devin M; Preuss, Kevin M; Wade, Michael J (2012) Evidence of a paucity of genes that interact with the mitochondrion on the X in mammals. Genome Biol Evol 4:763-8
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
Preuss, Kevin M; Lopez, Jacqueline A; Colbourne, John K et al. (2012) Identification of maternally-loaded RNA transcripts in unfertilized eggs of Tribolium castaneum. BMC Genomics 13:671
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

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