Publication List

@article{Mularoni2010,
title = {Natural selection drives the accumulation of amino acid tandem repeats in human proteins.},
author = {Mularoni, Loris and Ledda, Alice and Toll-Riera, Macarena and Albà, M Mar},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2877571&tool=pmcentrez&rendertype=abstract},
issn = {1549-5469},
year = {2010},
date = {2010-01-01},
journal = {Genome research},
volume = {20},
number = {6},
pages = {745--54},
abstract = {Amino acid tandem repeats are found in a large number of eukaryotic proteins. They are often encoded by trinucleotide repeats and exhibit high intra- and interspecies size variability due to the high mutation rate associated with replication slippage. The extent to which natural selection is important in shaping amino acid repeat evolution is a matter of debate. On one hand, their high frequency may simply reflect their high probability of expansion by slippage, and they could essentially evolve in a neutral manner. On the other hand, there is experimental evidence that changes in repeat size can influence protein-protein interactions, transcriptional activity, or protein subcellular localization, indicating that repeats could be functionally relevant and thus shaped by selection. To gauge the relative contribution of neutral and selective forces in amino acid repeat evolution, we have performed a comparative analysis of amino acid repeat conservation in a large set of orthologous proteins from 12 vertebrate species. As a neutral model of repeat evolution we have used sequences with the same DNA triplet composition as the coding sequences--and thus expected to be subject to the same mutational forces--but located in syntenic noncoding genomic regions. The results strongly indicate that selection has played a more important role than previously suspected in amino acid tandem repeat evolution, by increasing the repeat retention rate and by modulating repeat size. The data obtained in this study have allowed us to identify a set of 92 repeats that are postulated to play important functional roles due to their strong selective signature, including five cases with direct experimental evidence.},
keywords = {Amino Acid, Amino Acid Sequence, Amino Acids, Amino Acids: chemistry, Amino Acids: genetics, Animals, Genetic, Humans, Molecular Sequence Data, Proteins, Proteins: chemistry, Proteins: genetics, Repetitive Sequences, Selection, Sequence Homology}
}

@article{Mularoni2007,
title = {Highly constrained proteins contain an unexpectedly large number of amino acid tandem repeats.},
author = {Mularoni, Loris and Veitia, Reiner A and Albà, M Mar},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17196365},
issn = {0888-7543},
year = {2007},
date = {2007-01-01},
journal = {Genomics},
volume = {89},
number = {3},
pages = {316--25},
abstract = {Single-amino-acid tandem repeats are very common in mammalian proteins but their function and evolution are still poorly understood. Here we investigate how the variability and prevalence of amino acid repeats are related to the evolutionary constraints operating on the proteins. We find a significant positive correlation between repeat size difference and protein nonsynonymous substitution rate in human and mouse orthologous genes. This association is observed for all the common amino acid repeat types and indicates that rapid diversification of repeat structures, involving both trinucleotide slippage and nucleotide substitutions, preferentially occurs in proteins subject to low selective constraints. However, strikingly, we also observe a significant negative correlation between the number of repeats in a protein and the gene nonsynonymous substitution rate, particularly for glutamine, glycine, and alanine repeats. This implies that proteins subject to strong selective constraints tend to contain an unexpectedly high number of repeats, which tend to be well conserved between the two species. This is consistent with a role for selection in the maintenance of a significant number of repeats. Analysis of the codon structure of the sequences encoding the repeats shows that codon purity is associated with high repeat size interspecific variability. Interestingly, polyalanine and polyglutamine repeats associated with disease show very distinctive features regarding the degree of repeat conservation and the protein sequence selective constraints.},
keywords = {Amino Acid, Amino Acid Sequence, Animals, Complementary, Conserved Sequence, DNA, Evolution, Genetic, Humans, Mice, Molecular, Point Mutation, Proteins, Proteins: chemistry, Proteins: genetics, Repetitive Sequences, Selection, Trinucleotide Repeats}
}

@article{Alba2007a,
title = {Amino acid repeats and the structure and evolution of proteins.},
author = {Albà, M M and Tompa, P and Veitia, R A},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18753788},
issn = {1660-9263},
year = {2007},
date = {2007-01-01},
journal = {Genome dynamics},
volume = {3},
pages = {119--30},
abstract = {Many proteins have repeats or runs of single amino acids. The pathogenicity of some repeat expansions has fueled proteomic, genomic and structural explorations of homopolymeric runs not only in human but in a wide variety of other organisms. Other types of amino acid repetitive structures exhibit more complex patterns than homopeptides. Irrespective of their precise organization, repetitive sequences are defined as low complexity or simple sequences, as one or a few residues are particularly abundant. Prokaryotes show a relatively low frequency of simple sequences compared to eukaryotes. In the latter the percentage of proteins containing homopolymeric runs varies greatly from one group to another. For instance, within vertebrates, amino acid repeat frequency is much higher in mammals than in amphibians, birds or fishes. For some repeats, this is correlated with the GC-richness of the regions containing the corresponding genes. Homopeptides tend to occur in disordered regions of transcription factors or developmental proteins. They can trigger the formation of protein aggregates, particularly in 'disease' proteins. Simple sequences seem to evolve more rapidly than the rest of the protein/gene and may have a functional impact. Therefore, they are good candidates to promote rapid evolutionary changes. All these diverse facets of homopolymeric runs are explored in this review.},
keywords = {Amino Acid, Animals, Base Composition, Evolution, Humans, Molecular, Open Reading Frames, Open Reading Frames: genetics, Peptides, Peptides: chemistry, Proteins, Proteins: chemistry, Proteins: genetics, Repetitive Sequences}
}

@article{Mularoni2006,
title = {Mutation patterns of amino acid tandem repeats in the human proteome.},
author = {Mularoni, Loris and Guigó, Roderic and Albà, M Mar},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1557989&tool=pmcentrez&rendertype=abstract},
issn = {1465-6914},
year = {2006},
date = {2006-01-01},
journal = {Genome biology},
volume = {7},
number = {4},
pages = {R33},
abstract = {Amino acid tandem repeats are found in nearly one-fifth of human proteins. Abnormal expansion of these regions is associated with several human disorders. To gain further insight into the mutational mechanisms that operate in this type of sequence, we have analyzed a large number of mutation variants derived from human expressed sequence tags (ESTs).},
keywords = {Amino Acid, Amino Acid Substitution, Amino Acid: genetics, Codon, Expressed Sequence Tags, Genetic, Humans, Mutation, Polymorphism, Protein, Proteome, Proteome: genetics, Repetitive Sequences, Sequence Analysis}
}

@article{Huang2004,
title = {Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes.},
author = {Huang, Hui and Winter, Eitan E and Wang, Huajun and Weinstock, Keith G and Xing, Heming and Goodstadt, Leo and Stenson, Peter D and Cooper, David N and Smith, Douglas and Albà, M Mar and Ponting, Chris P and Fechtel, Kim},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=463309&tool=pmcentrez&rendertype=abstract},
issn = {1465-6914},
year = {2004},
date = {2004-01-01},
journal = {Genome biology},
volume = {5},
number = {7},
pages = {R47},
abstract = {Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change.},
keywords = {Amino Acid, Amino Acid: genetics, Animal, Animals, Chromosome Mapping, Chromosome Mapping: methods, Conserved Sequence, Conserved Sequence: genetics, Disease Models, Evolution, Fishes, Fishes: genetics, Fungal, Fungal: genetics, Genes, Genes: genetics, Genes: physiology, Genetic, Genetic Diseases, Genome, Helminth, Helminth: genetics, human, Humans, Inborn, Inborn: genetics, Inborn: physiopathology, Insect, Insect: genetics, Mice, Molecular, Mutagenesis, Mutagenesis: genetics, Nucleic Acid, Nucleotides, Nucleotides: genetics, Point Mutation, Point Mutation: genetics, Rats, Repetitive Sequences, Selection, Sequence Homology, Trinucleotide Repeat Expansion, Trinucleotide Repeat Expansion: genetics}
}

@article{Alba2004,
title = {Comparative analysis of amino acid repeats in rodents and humans.},
author = {Albà, M Mar and Guigó, Roderic},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=383298&tool=pmcentrez&rendertype=abstract},
issn = {1088-9051},
year = {2004},
date = {2004-01-01},
journal = {Genome research},
volume = {14},
number = {4},
pages = {549--54},
abstract = {Amino acid tandem repeats, also called homopolymeric tracts, are extremely abundant in eukaryotic proteins. To gain insight into the genome-wide evolution of these regions in mammals, we analyzed the repeat content in a large data set of rat-mouse-human orthologs. Our results show that human proteins contain more amino acid repeats than rodent proteins and that trinucleotide repeats are also more abundant in human coding sequences. Using the human species as an outgroup, we were able to address differences in repeat loss and repeat gain in the rat and mouse lineages. In this data set, mouse proteins contain substantially more repeats than rat proteins, which can be at least partly attributed to a higher repeat loss in the rat lineage. The data are consistent with a role for trinucleotide slippage in the generation of novel amino acid repeats. We confirm the previously observed functional bias of proteins with repeats, with overrepresentation of transcription factors and DNA-binding proteins. We show that genes encoding amino acid repeats tend to have an unusually high GC content, and that differences in coding GC content among orthologs are directly related to the presence/absence of repeats. We propose that the different GC content isochore structure in rodents and humans may result in an increased amino acid repeat prevalence in the human lineage.},
keywords = {Amino Acid, Amino Acid: genetics, Amino Acid: physiology, Animals, Chromosome Mapping, Chromosome Mapping: methods, Chromosome Mapping: statistics & numerical data, Computational Biology, Computational Biology: methods, Computational Biology: statistics & numerical data, GC Rich Sequence, GC Rich Sequence: genetics, Humans, Mice, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: physiology, Rats, Repetitive Sequences, Trinucleotide Repeats, Trinucleotide Repeats: genetics}
}

@article{Alba2002,
title = {Detecting cryptically simple protein sequences using the SIMPLE algorithm.},
author = {Albà, M Mar and Laskowski, Roman A and Hancock, John M},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12050063},
issn = {1367-4803},
year = {2002},
date = {2002-01-01},
journal = {Bioinformatics (Oxford, England)},
volume = {18},
number = {5},
pages = {672--8},
abstract = {Low-complexity or cryptically simple sequences are widespread in protein sequences but their evolution and function are poorly understood. To date methods for the detection of low complexity in proteins have been directed towards the filtering of such regions prior to sequence homology searches but not to the analysis of the regions per se. However, many of these regions are encoded by non-repetitive DNA sequences and may therefore result from selection acting on protein structure and/or function.},
keywords = {Algorithms, Amino Acid, Amino Acid Sequence, Amino Acid: genetics, Databases, Genetic, Genetic Variation, Internet, Minisatellite Repeats, Minisatellite Repeats: genetics, Models, Molecular Sequence Data, Protein, Protein: methods, Proteins, Proteins: chemistry, Repetitive Sequences, Saccharomyces cerevisiae, Saccharomyces cerevisiae: genetics, Sensitivity and Specificity, Sequence Analysis, Sequence Homology, Software, Statistical}
}