Tissue-driven Hypothesis with Gene Ontology (GO) Analysis

Su, Zhixi; Huang, Yong; Gu, Xun

doi:10.1007/s10439-007-9269-y

Cited by 9 publications

(6 citation statements)

References 25 publications

(25 reference statements)

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“…In particular, we discuss in some details about the translational selection hypothesis [12-14]. This theory demonstrates that one of major components in the functional constraint imposed in the protein sequence is the minimization of misfolding burden, or the sequence requirement to retain the capability to fold into the correct, functional protein structure.…”

Section: Testing the Hypothesismentioning

confidence: 99%

Genome factor and gene pleiotropy hypotheses in protein evolution

Zeng

2010

Biology Direct

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The debate of genomic correlations between sequence conservation, protein connectivity, gene essentiality and gene expression, has generated a number of new hypotheses that are challenging the classical framework of molecular evolution. For instance, the translational selection hypothesis claims that the determination of the rate of protein evolution is the protein stability to avoid the misfolding toxicity. In this short article, we propose that gene pleiotropy, the capacity for affecting multiple phenotypes, may play a vital role in molecular evolution. We discuss several approaches to testing this hypothesis.ReviewersThis article was reviewed by Dr Eugene Koonin, Dr Arcady Mushegian and Dr Claus Wilke.

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Section: Testing the Hypothesismentioning

confidence: 99%

Genome factor and gene pleiotropy hypotheses in protein evolution

Zeng

2010

Biology Direct

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“…We also find that mRNA expression abundance contributes significantly to some but not all properties. Interestingly, expression level is correlated with expression breadth [18], but not with phyletic age; under our hypothesis, the observed result suggests that ancient cellular functions do not generally require large protein numbers, but that expression levels are rather driven by tissue-specific effects [9]. …”

Section: Resultsmentioning

confidence: 97%

“…The duplication thus creates two gene copies with the same phyletic age, but very different expression profiles [7,8]; other changes of gene attributes (e.g., sequence changes to optimize tissue-specific function) might follow. Furthermore, genes expressed in different tissues may be under different constraints, resulting in variable evolutionary rates across proteins with similar expression breadth [9]. Another important factor known to influence gene structure and evolution is expression abundance [10-12].…”

Section: Introductionmentioning

confidence: 99%

Human functional genetic studies are biased against the medically most relevant primate-specific genes

Hao

Wan

et al. 2010

BMC Evol Biol

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BackgroundMany functional, structural and evolutionary features of human genes have been observed to correlate with expression breadth and/or gene age. Here, we systematically explore these correlations.ResultsGene age and expression breadth are strongly correlated, but contribute independently to the variation of functional, structural and evolutionary features, even when we take account of variation in mRNA expression level. Human genes without orthologs in distant species ('young' genes) tend to be tissue-specific in their expression. As computational inference of gene function often relies on the existence of homologs in other species, and experimental characterization is facilitated by broad and high expression, young, tissue-specific human genes are often the least characterized. At the same time, young genes are most likely to be medically relevant.ConclusionsOur results indicate that functional characterization of human genes is biased against young, tissue-specific genes that are mostly medically relevant. The biases should not be taken lightly because they may pose serious obstacles to our understanding of the molecular basis of human diseases. Future studies should thus be designed to specifically explore the properties of primate-specific genes.

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“…Neural tissues developed from ectoderm were the most conserved sub-group. The expression pattern of genes in these tissues is more conservative to each other: more conserved individual genes, more conserved GO modules, less differentially expressed GO modules and more significantly correlated GO modules, compared with tissues developed from mesendoderm [8]. Notably, tissues developed from endoderm appear to have a large number of differentially expressed genes, which might be related to the large functional variation of these tissues and the long developing time in embryo.…”

Section: Discussionmentioning

confidence: 99%

“…Results from these studies showed that different tissues shared a large number of ubiquitously expressed genes and the tissue specific genes are more likely to reveal tissue-specific function. A gene set (Gene Ontology - GO) based analysis proposed a “tissue-driven” hypothesis which describes the relationship between the stabilizing constraints on tissue-specific gene expression and individual GO categories [8]. …”

Section: Introductionmentioning

confidence: 99%

Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

et al. 2010

BMC Bioinformatics

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BackgroundEmbryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity.ResultsWe performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues.ConclusionThe results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes.

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Tissue-driven Hypothesis with Gene Ontology (GO) Analysis

Cited by 9 publications

References 25 publications

Genome factor and gene pleiotropy hypotheses in protein evolution

Genome factor and gene pleiotropy hypotheses in protein evolution

Human functional genetic studies are biased against the medically most relevant primate-specific genes

Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

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