Biomedical subjects

Ignacio Marín

Publications and source records attributed to Ignacio Marín.

8 recordsLinked to original sources

PubMed2004

Iterative cluster analysis of protein interaction data.

MOTIVATION: Generation of fast tools of hierarchical clustering to be applied when distances among elements of a set are constrained, causing frequent distance ties, as happens in protein interaction data. RESULTS: We present in this work the program UVCLUSTER, that iteratively explores distance datasets using hierarchical clustering. Once the user selects a group of proteins, UVCLUSTER converts the set of primary distances among them (i.e. the minimum number of steps, or interactions, required to connect two proteins) into secondary distances that measure the strength of the connection between each pair of proteins when the interactions for all the proteins in the group are considered. We show that this novel strategy has advantages over conventional clustering methods to explore protein-protein interaction data. UVCLUSTER easily incorporates the information of the largest available interaction datasets to generate comprehensive primary distance tables. The versatility, simplicity of use and high speed of UVCLUSTER on standard personal computers suggest that it can be a benchmark analytical tool for interactome data analysis. AVAILABILITY: The program is available upon request from the authors, free for academic users. Additional information available at http://www.uv.es/genomica/UVCLUSTER.

Actins↗

PubMed2004

Parkin and relatives: the RBR family of ubiquitin ligases.

Mutations in the parkin gene cause autosomal-recessive juvenile parkinsonism. Parkin encodes a ubiquitin-protein ligase characterized by having the RBR domain, composed of two RING fingers plus an IBR/DRIL domain. The RBR family is defined as the group of genes whose products contain an RBR domain. RBR family members exist in all eukaryotic species for which significant sequence data is available, including animals, plants, fungi, and several protists. The integration of comparative genomics with structural and functional data allows us to conclude that RBR proteins have multiple roles, not only in protein quality control mechanisms, but also as indirect regulators of transcription. A recently formulated hypothesis, based on a case of gene fusion, suggested that RBR proteins may be often part of cullin-containing ubiquitin ligase complexes. Recent data on Parkin protein agrees with that hypothesis. We discuss the involvement of RBR proteins in several neurodegenerative diseases and cancer.

Animals↗

PubMed2004

New insights into the evolutionary history of type 1 rhodopsins.

Type 1 (archaeal) rhodopsins and related rhodopsin-like proteins had been described in a few halophile archaea, gamma-proteobacteria, a single cyanobacteria, some fungi, and a green alga. In exhaustive database searches, we detected rhodopsin-related sequences derived not only from additional fungal species but also from organisms belonging to three groups in which opsins had hitherto not been described: the alpha-proteobacterium Magnetospirillum magnetotacticum, the cryptomonad alga Guillardia theta, and the dinoflagellate Pyrocystis lunula. Putative plant and human type 1 rhodopsin sequences found in the databases are demonstrated to be contaminants of fungal origin. However, a highly diverged sequence supposedly from the plant Oryza sativa was found that is, together with the Pyrocystis sequence, quite similar to gamma-proteobacterial rhodopsins. These close relationships suggest that at least one horizontal gene transfer event involving rhodopsin genes occurred between prokaryotes and eukaryotes. Alternative hypotheses to explain the current phylogenetic range of type 1 rhodopsins are suggested. The broader phylogenetic range found is compatible with an ancient origin of type 1 rhodopsins, their patchy distribution being caused by losses in multiple lineages. However, the possibility of ancient horizontal transfer events between distant relatives cannot be dismissed.

Amino Acid Sequence↗

PubMed2003

Evolutionary and structural analyses of GDAP1, involved in Charcot-Marie-Tooth disease, characterize a novel class of glutathione transferase-related genes.

Mutations in the Ganglioside-induced differentiation-associated protein-1 (GDAP1) gene cause autosomal recessive Charcot-Marie-Tooth disease type 4A. The protein encoded by GDAP1 shows clear similarity to glutathione transferases (also known as glutathione S-transferases or GSTs). The human genome contains a paralog of GDAP1 called GDAP1L1. Using comparative genomics, we show that orthologs of GDAP1 and GDAP1L1 are found in mammals, birds, amphibians, and fishes. Likely orthologs of those genes in invertebrates and a low but consistent similarity with some plant and eubacterial genes have also been found. We demonstrate that GDAP1 and GDAP1L1 do not belong to any of the known classes of GST genes. In addition to having distinctive sequences, GDAP1 and its relatives are also characterized by an extended region in GST domain II, absent in most other GSTs, and by a C-terminal end predicted to contain transmembrane domains. Mutations affecting any of those characteristic domains are known to cause Charcot-Marie-Tooth disease. These features define the GDAP1 class of GST-like proteins.

Amino Acid Sequence↗

PubMed2003

Selection on coding regions determined Hox7 genes evolution.

The important role of Hox genes in determining the regionalization of the body plan of the vertebrates makes them invaluable candidates for evolutionary analyses regarding functional and morphological innovation. Gene duplication and gene loss led to a variable number of Hox genes in different vertebrate lineages. The evolutionary forces determining the conservation or loss of Hox genes are poorly understood. In this study, we show that variable selective pressures acted on Hox7 genes in different evolutionary lineages, with episodes of positive selection occurring after gene duplications. Tests for functional divergence in paralogs detected significant differentiation in a region known to modulate HOX7 protein activity. Our results show that both positive and negative selection on coding regions are influencing Hox7 genes evolution.

Amino Acid Sequence↗

PubMed2003

Evolution of chromatin-remodeling complexes: comparative genomics reveals the ancient origin of "novel" compensasome genes.

Dosage compensation in Drosophila is mediated by a complex, called compensasome, composed of at least five proteins and two noncoding RNAs. Genes encoding compensasome proteins have been collectively named male-specific lethals or msls. Recent work showed that three of the Drosophila msls (msl-3, mof, and mle) have an ancient origin. In this study, I describe likely orthologues of the two remaining msls, msl-1 and msl-2, in several invertebrates and vertebrates. The MSL-2 protein is the only one found in Drosophila and vertebrate genomes that contains both a RING finger and a peculiar type of CXC domain, related to the one present in Enhancer of Zeste proteins. MSL-1 also contains two evolutionarily conserved domains: a leucine zipper and a second characteristic region, described here for the first time, which I have called the PEHE domain. These two domains are present in the likely orthologues of MSL-1 as well as in other genes in several invertebrate and vertebrate species. Although it cannot be excluded that the compensasome complex is a recent evolutionary novelty, these results shows that all msls are found in mammals, suggesting that protein complexes related to the compensasome may be present in mammalian species. Metazoans that lack several of the msls, such as Caenorhabditis elegans, cannot contain compensasomes. The evolutionary relationships of the compensasome and the NuA4 complex, another chromatin-remodeling complex that contains related subunits, are discussed.

Amino Acid Motifs↗

PubMed2002

Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily.

Genes of the RBR family are characterized by the RBR signature (two RING finger domains separated by an IBR/DRIL domain). The RBR family is widespread in eukaryotes, with numerous members in animals (mammals, Drosophila, Caenorhabditis) and plants (Arabidopsis). But yeasts, such as Saccharomyces cerevisiae or Schizosaccharomyces pombe, contain only two RBR genes. We determined the phylogenetic relationships and the most likely orthologs in different species of several family members for which functional data are available. These include: (1) parkin, whose mutations are involved in forms of familial Parkinson's disease; (2) the ariadne genes, recently characterized in Drosophila and mammals; (3) XYbp and Dorfin, two mammalian genes whose products interact with the centrosome; (4) XAP3, RBCK1, and UIP28, mammalian genes encoding Protein Kinase-C-binding proteins; and (5) ARA54, an androgen receptor coactivator. Because several of these genes are involved in ubiquitination, we used phylogenetic and structural analyses to explore the hypothesis that all RBR proteins might play a role in ubiquitination. We show that the involvement of RBR proteins in ubiquitination predates the animals-plants-fungi divergence. On the basis of the evidence provided by cases of gene fusion, we suggest that Ariadne proteins interact with cullin domain-containing proteins to form complexes with ubiquitin-ligase activity.

Animals↗

PubMed2001

The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease.

We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.

Age of Onset↗