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Douglas L Crawford

Publications and source records attributed to Douglas L Crawford.

9 recordsLinked to original sources
PubMed2006

Neutral and adaptive variation in gene expression.

Variation among populations in gene expression should be related to the accumulation of random-neutral changes and evolution by natural selection. The following evolutionary analysis has general applicability to biological and medical science because it accounts for genetic relatedness and identifies patterns of expression variation that are affected by natural selection. To identify genes evolving by natural selection, we allocate the maximum among-population variation to genetic distance and then examine the remaining variation relative to a hypothesized important ecological parameter (temperature). These analyses measure the expression of metabolic genes in common-gardened populations of the fish Fundulus heteroclitus whose habitat is distributed along a steep thermal gradient. Although much of the variation in gene expression fits a null model of neutral drift, the variation in expression for 22% of the genes that regress with habitat temperature was far greater than could be accounted for by genetic distance alone. The most parsimonious explanation for among-population variation for these genes is evolution by natural selection. In addition, many metabolic genes have patterns of variation incongruent with neutral evolution: They have too much or too little variation. These patterns of biological variation in expression may reflect important physiological or ecological functions.

Animals↗
PubMed2006

Variation within and among species in gene expression: raw material for evolution.

Heritable variation in regulatory or coding regions is the raw material for evolutionary processes. The advent of microarrays has recently promoted examination of the extent of variation in gene expression within and among taxa and examination of the evolutionary processes affecting variation. This review examines these issues. We find: (i) microarray-based measures of gene expression are precise given appropriate experimental design; (ii) there is large inter-individual variation, which is composed of a minor nongenetic component and a large heritable component; (iii) variation among populations and species appears to be affected primarily by neutral drift and stabilizing selection, and to a lesser degree by directional selection; and (iv) neutral evolutionary divergence in gene expression becomes nonlinear with greater divergence times due to functional constraint. Evolutionary analyses of gene expression reviewed here provide unique insights into partitioning of regulatory variation in nature. However, common limitations of these studies include the tendency to assume a linear relationship between expression divergence and species divergence, and failure to test explicit hypotheses that involve the ecological context of evolutionary divergence.

Animals↗
PubMed2005

Variation in tissue-specific gene expression among natural populations.

BACKGROUND: Variation in gene expression is extensive among tissues, individuals, strains, populations and species. The interactions among these sources of variation are relevant for physiological studies such as disease or toxic stress; for example, it is common for pathologies such as cancer, heart failure and metabolic disease to be associated with changes in tissue-specific gene expression or changes in metabolic gene expression. But how conserved these differences are among outbred individuals and among populations has not been well documented. To address this we examined the expression of a selected suite of 192 metabolic genes in brain, heart and liver in three populations of the teleost fish Fundulus heteroclitus using a highly replicated experimental design. RESULTS: Half of the genes (48%) were differentially expressed among individuals within a population-tissue group and 76% were differentially expressed among tissues. Differences among tissues reflected well established tissue-specific metabolic requirements, suggesting that these measures of gene expression accurately reflect changes in proteins and their phenotypic effects. Remarkably, only a small subset (31%) of tissue-specific differences was consistent in all three populations. CONCLUSIONS: These data indicate that many tissue-specific differences in gene expression are unique to one population and thus are unlikely to contribute to fundamental differences between tissue types. We suggest that those subsets of treatment-specific gene expression patterns that are conserved between taxa are most likely to be functionally related to the physiological state in question.

Animals↗
PubMed2005

Fish as models for environmental genomics.

Fish offer important advantages for defining the organism-environment interface and responses to natural or anthropogenic stressors. Genomic approaches using fish promise increased investigative power, and have already provided insights into the mechanisms that underlie short-term and long-term environmental adaptations. The range of fish species for which genomic resources are available is increasing, but will require significant further expansion for the optimal application of fish environmental genomics.

Adaptation, Physiological↗
PubMed2004

FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression.

BACKGROUND: While studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes. RESULTS: We describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P < 0.001) enrichment in genes associated with amine metabolism. CONCLUSION: The methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at http://genomics.rsmas.miami.edu/funnybase/super_craw4/. Data and source code are available by request at jpaschall@bioinfobase.umkc.edu.

Animals↗
PubMed2004

Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus.

Individual variation in gene expression is important for evolutionary adaptation and susceptibility to diseases and pathologies. 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.

Animals↗
PubMed2002

Variation in gene expression within and among natural populations.

Evolution may depend more strongly on variation in gene expression than on differences between variant forms of proteins. Regions of DNA that affect gene expression are highly variable, containing 0.6% polymorphic sites. These naturally occurring polymorphic nucleotides can alter in vivo transcription rates. Thus, one might expect substantial variation in gene expression between individuals. But the natural variation in mRNA expression for a large number of genes has not been measured. Here we report microarray studies addressing the variation in gene expression within and between natural populations of teleost fish of the genus Fundulus. We observed statistically significant differences in expression between individuals within the same population for approximately 18% of 907 genes. Expression typically differed by a factor of 1.5, and often more than 2.0. Differences between populations increased the variation. Much of the variation between populations was a positive function of the variation within populations and thus is most parsimoniously described as random. Some genes showed unexpected patterns of expression--changes unrelated to evolutionary distance. These data suggest that substantial natural variation exists in gene expression and that this quantitative variation is important in evolution.

Analysis of Variance↗
PubMed2002

Evolution of Sp transcription factors.

The Sp family of transcription factors binds GC-rich DNA sequences. The ubiquitously expressed Sp1 and Sp3 have been well characterized in mammals. Presented here is the characterization of the only Sp protein expressed in the liver or heart tissue of the teleost fish Fundulus heteroclitus. This protein, fSp3, is most similar to and homologous with mammalian Sp3 proteins. The evolution of the Sp transcription family is described, with Sp1 and Sp3 representing the most recent duplication of the Sp family. Sp4 appears to be the most ancestral member. Sp1, Sp3, and Sp4 form a monophyletic group without Sp2. Sp2 is the least similar of the Sp family and is more similar to the non-Sp transcription factors. These results suggest that Sp2 should not be considered a member of the Sp family. Only two domains (zinc fingers and B domain) share similarity outside the Sp family. The zinc fingers are homologous to other GC-binding domains, yet the B domain is homologous to protein-protein interacting domains in the CCAAT-binding/NF-Y transcription factor families. These results suggest that these different domains have different evolutionary histories.

Amino Acid Sequence↗