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Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus


Individual variation in gene expression is important for evolutionary adaptation1,2 and susceptibility to diseases and pathologies3,4. In this study, we address the functional importance of this variation by comparing cardiac metabolism to patterns of mRNA expression using microarrays. There is extensive variation in both cardiac metabolism and the expression of metabolic genes among individuals of the teleost fish Fundulus heteroclitus from natural outbred populations raised in a common environment: metabolism differed among individuals by a factor of more than 2, and expression levels of 94% of genes were significantly different (P < 0.01) between individuals in a population. This unexpectedly high variation in metabolic gene expression explains much of the variation in metabolism, suggesting that it is biologically relevant. The patterns of gene expression that are most important in explaining cardiac metabolism differ between groups of individuals. Apparently, the variation in metabolism seems to be related to different patterns of gene expression in the different groups of individuals. The magnitude of differences in gene expression in these groups is not important; large changes in expression have no greater predictive value than small changes. These data suggest that variation in physiological performance is related to the subtle variation in gene expression and that this relationship differs among individuals.

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Figure 1: Cardiac metabolism among 16 individuals (identified by numbers) from populations from northern Maine (M) and southern Georgia (G) using three substrates: 5 mM glucose; fatty acid (1 mM palmitic acid bound to bovine serum albumin); and LKA (5 mM lactate, 5 mM each of two ketones: hydroxybutyrate and acetoacetate, and 0.1% ethanol).
Figure 2: Significant differences in gene expression in a population versus difference relative to the population mean.
Figure 3: Hierarchical cluster of metabolic gene expression.
Figure 4: Pattern of gene expression arranged according to metabolic rates.
Figure 5: Different patterns of gene expression explain the variation in metabolism.
Figure 6: Relative changes versus correlation with metabolism.


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We thank S. Hand for use of the pizeo-electric microarray printer and for critical but insightful thoughts and reading of the manuscript and G. Churchill, A. Whitehead, A. Clark and M. Q. Martindale for discussions and critical reading of the manuscript. This work was supported by the US National Science Foundation (Division of Ocean Sciences) and the US National Institutes of Health (National Heart, Lung, and Blood Institute and National Institute of Environmental Health Sciences).

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Correspondence to Douglas L Crawford.

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Supplementary information

Supplementary Table 1

Metabolic rates for 16 male individuals utilizing glucose, fatty acid or lactate-ketones-alcohol. (PDF 37 kb)

Supplementary Table 2

Summary table for all genes. (PDF 33 kb)

Supplementary Table 3

Differences between populations in gene expression. (PDF 36 kb)

Supplementary Table 4

Correlations for patterns of gene expression among individuals within a group and between group means. (PDF 95 kb)

Supplementary Table 5

Genes and descriptions of enzymes in the three major metabolic pathways. (PDF 56 kb)

Supplementary Table 6

Principal components for the three major metabolic pathways. (PDF 45 kb)

Supplementary Table 7

Stepwise regression and associated statistics. (PDF 2138 kb)

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Oleksiak, M., Roach, J. & Crawford, D. Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus. Nat Genet 37, 67–72 (2005).

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