This proposal seeks to quantify the expression of thousands of mRNAs using microarray technologies in order to determine the range and magnitude of variation in mRNA expression among individuals and populations and to apply evolutionary analyses in order to determine how much of this variation is either neutral or, alternatively, biologically important. Based on our knowledge of genetic variation, many of the changes in mRNA expression will represent random neutral genetic differences, differences that do not produce biologically important phenotypic changes. The application of evolutionary analyses can identify these random variations in mRNA expression. Alternatively, some of these variations in mRNA expression have evolved by natural selection and thus are biologically important. Among the teleost fish Fundulus, populations in four different species have independently evolved adaptive differences in glycolytic enzyme expression and cardiac metabolism (Pierce. V. A. and D. L. Crawford, 1997, Science 275:256-259). These four species provide replicate populations to inquire whether similar changes in gene expression have evolved. This proposed research seeks to take advantage of the differences among populations and species of Fundulus to identify which variations in mRNA expression are adaptively important and relate these adaptive gene complexes to the variation in cardiac metabolism. Quantifying genome-wide variation in mRNA expression using vertebrate species that have evolved differences in metabolism and gene expression addresses basic questions concerning the importance of all the enzymes in effecting a change in metabolic flux. This evolutionary approach provides the means to distinguish random variation from adaptively important variation and will lead to the discovery of patterns of mRNA expression that affect cardiac physiology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL065470-01A2
Application #
6436157
Study Section
Genome Study Section (GNM)
Program Officer
Wang, Lan-Hsiang
Project Start
2002-07-20
Project End
2003-06-30
Budget Start
2002-07-20
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$346,633
Indirect Cost
Name
University of Missouri Kansas City
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800772162
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Everett, Meredith V; Antal, Corina E; Crawford, Douglas L (2012) The effect of short-term hypoxic exposure on metabolic gene expression. J Exp Zool A Ecol Genet Physiol 317:9-23
Everett, Meredith V; Crawford, Douglas L (2010) Adaptation versus allometry: population and body mass effects on hypoxic metabolism in Fundulus grandis. Physiol Biochem Zool 83:182-90
Scott, Cinda P; VanWye, Jeff; McDonald, M Danielle et al. (2009) Technical analysis of cDNA microarrays. PLoS One 4:e4486
Scott, Cinda P; Williams, Dean A; Crawford, Douglas L (2009) The effect of genetic and environmental variation on metabolic gene expression. Mol Ecol 18:2832-43
Whitehead, Andrew; Crawford, Douglas L (2006) Neutral and adaptive variation in gene expression. Proc Natl Acad Sci U S A 103:5425-30
Whitehead, Andrew; Crawford, Douglas L (2005) Variation in tissue-specific gene expression among natural populations. Genome Biol 6:R13
Oleksiak, Marjorie F; Roach, Jennifer L; Crawford, Douglas L (2005) Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus. Nat Genet 37:67-72
Paschall, Justin E; Oleksiak, Marjorie F; VanWye, Jeffrey D et al. (2004) FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression. BMC Genomics 5:96