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Cardiovascular Genomics: New Pathophysiological Concepts pp 29–40Cite as

Using Comparative Genome Analysis to Find Interaction Partners for Frataxin

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Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 242))

Abstract

The sequencing of complete genomes has provided the opportunity, not only to interpret the function of a protein within its proteomic context, but also to predict new functional interactions between proteins using comparative genome analysis [1]. Various methods have been proposed and demonstrated to predict functional interaction between proteins based on the genomic context of their genes [2 3 4 5]. These methods are all based on variations of the idea that genes that are somehow associated with each other on the genome tend to encode proteins that functionally interact. The types of genomic association that they use are either a) the fusion of genes; b) the conservation of gene order, e.g. when genes are located in operons; c) the co-occurrence of genes in genomes (also called ‘phylogenetic profiles’). A systematic analysis of the correlation between on the one hand the type of genomic context and on the other hand the type of functional interaction shows that conservation of genomic context can indeed be a reliable indication of a functional interaction. The functional interactions that are reflected in the conservation of genomic context include a wide variety of relations between proteins, including direct physical interactions but also less direct ones, like being part of the same metabolic or regulatory pathway. When there is prior knowledge about a protein’s involvement in a process, yet the exact function of the protein is not known, the co-occurrence of genes in genomes can more specifically pinpoint in which sub-process the protein plays a role [6 7]. Here we use genome comparisons to predict functional interactions for frataxin, a mitochondrial protein that has no detectable homologs with known function and that presently has a unique fold [8 9].Severely reduced levels of frataxin cause the disease Friedreich’s ataxia [10], which is characterized by degeneration of large sensory neurons and spinocerebellar tracts, cardiomyopathy and increased likelihood of diabetes [11]. In mitochondria, reduced levels of frataxin result in the absence of iron-sulfur (Fe-S) cluster dependent enzymes, accumulation of iron deposits, DNA damage and oxidative stress [12]. Based on such observations the main hypothesis about frataxin’s function is that it is directly involved in iron homeostasis of the mitochondria. Alternatively it has been

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Authors
  1. M. A. Huynen
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Editors and Affiliations

  1. Academic Hospital Maastricht, Maastricht, Germany

    Pieter A. Doevendans MD

  2. Klinikum Grosshadern, Munich, Germany

    Stefan Kääb

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Huynen, M.A. (2002). Using Comparative Genome Analysis to Find Interaction Partners for Frataxin. In: Doevendans, P.A., Kääb, S. (eds) Cardiovascular Genomics: New Pathophysiological Concepts. Developments in Cardiovascular Medicine, vol 242. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1005-5_4

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  • DOI: https://doi.org/10.1007/978-1-4615-1005-5_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5347-8

  • Online ISBN: 978-1-4615-1005-5

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