Insights into the Molecular Evolution of the PDZ/LIM Family and Identification of a Novel Conserved Protein Motif

The PDZ and LIM domain-containing protein family is encoded by a diverse group of genes whose phylogeny has currently not been analyzed. In mammals, ten genes are found that encode both a PDZ- and one or several LIM-domains. These genes are: ALP, RIL, Elfin (CLP36), Mystique, Enigma (LMP-1), Enigma homologue (ENH), ZASP (Cypher, Oracle), LMO7 and the two LIM domain kinases (LIMK1 and LIMK2). As conventional alignment and phylogenetic procedures of full-length sequences fell short of elucidating the evolutionary history of these genes, we started to analyze the PDZ and LIM domain sequences themselves. Using information from most sequenced eukaryotic lineages, our phylogenetic analysis is based on full-length cDNA-, EST-derived- and genomic- PDZ and LIM domain sequences of over 25 species, ranging from yeast to humans. Plant and protozoan homologs were not found. Our phylogenetic analysis identifies a number of domain duplication and rearrangement events, and shows a single convergent event during evolution of the PDZ/LIM family. Further, we describe the separation of the ALP and Enigma subfamilies in lower vertebrates and identify a novel consensus motif, which we call ‘ALP-like motif’ (AM). This motif is highly-conserved between ALP subfamily proteins of diverse organisms. We used here a combinatorial approach to define the relation of the PDZ and LIM domain encoding genes and to reconstruct their phylogeny. This analysis allowed us to classify the PDZ/LIM family and to suggest a meaningful model for the molecular evolution of the diverse gene architectures found in this multi-domain family

The PinkThing for analysing ChIP profiling data in their genomic context

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Oxygen dependence of metabolism and cellular adaptation in vertebrate muscles: a review

The key roles the cardiovascular system play in the complex distribution of blood, and consequently oxygen, have been extensively studied in vertebrates. Numerous studies have also revealed the complex and varied ways in which tissues cope with compromised oxygen supply. The links between these two processes are the subject of much current research. This article aims to review how blood supply influences tissue oxygenation and affects metabolism, and how this might have played a role in the evolution of the complex muscle arrangements which characterise vertebrates. Muscle tissue is the greatest proportion of body mass in most vertebrates and undergoes dramatic alterations in metabolism and associated oxygen flux. Special attention is given to the myotome of fishes, in which the partitioning of the fibre types contrasts with the mosaic arrangement of tetrapods. This gives us the opportunity to study pure whole vascularised muscle blocks, rather than single fibres, and further explore the interrelationship between oxygen supply and tissue energetics.<br /