Amino Acid Animals Computational Biology Databases de novo gene DNA Evolution Genetic Genome human Humans Mice Molecular Molecular Sequence Data Proteins Proteins: chemistry Proteins: genetics Repetitive Sequences ribosome profiling RNA-Seq Selection Sequence Analysis Sequence Homology transcriptomics yeast
2007 |
Mularoni, Loris, Veitia, Reiner A, Albà, M Mar Highly constrained proteins contain an unexpectedly large number of amino acid tandem repeats. (Article) Genomics, 89 (3), pp. 316–25, 2007, ISSN: 0888-7543. (Abstract | Links | BibTeX | Tags: 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{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} } 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. |
Bellora, Nicolás, Farré, Domènec, Mar Albà, M PEAKS: identification of regulatory motifs by their position in DNA sequences. (Article) Bioinformatics (Oxford, England), 23 (2), pp. 243–4, 2007, ISSN: 1367-4811. (Abstract | Links | BibTeX | Tags: Algorithms, Automated, Automated: methods, Base Sequence, Chromosome Mapping, Chromosome Mapping: methods, DNA, DNA: genetics, DNA: methods, Molecular Sequence Data, Nucleic Acid, Nucleic Acid: genetics, Pattern Recognition, Regulatory Sequences, Sequence Alignment, Sequence Alignment: methods, Sequence Analysis, Software, Transcriptional Activation, Transcriptional Activation: genetics) @article{Bellora2007a, title = {PEAKS: identification of regulatory motifs by their position in DNA sequences.}, author = {Bellora, Nicolás and Farré, Domènec and Mar Albà, M}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17098773}, issn = {1367-4811}, year = {2007}, date = {2007-01-01}, journal = {Bioinformatics (Oxford, England)}, volume = {23}, number = {2}, pages = {243--4}, abstract = {Many DNA functional motifs tend to accumulate or cluster at specific gene locations. These locations can be detected, in a group of gene sequences, as high frequency 'peaks' with respect to a reference position, such as the transcription start site (TSS). We have developed a web tool for the identification of regions containing significant motif peaks. We show, by using different yeast gene datasets, that peak regions are strongly enriched in experimentally-validated motifs and contain potentially important novel motifs. AVAILABILITY: http://genomics.imim.es/peaks}, keywords = {Algorithms, Automated, Automated: methods, Base Sequence, Chromosome Mapping, Chromosome Mapping: methods, DNA, DNA: genetics, DNA: methods, Molecular Sequence Data, Nucleic Acid, Nucleic Acid: genetics, Pattern Recognition, Regulatory Sequences, Sequence Alignment, Sequence Alignment: methods, Sequence Analysis, Software, Transcriptional Activation, Transcriptional Activation: genetics} } Many DNA functional motifs tend to accumulate or cluster at specific gene locations. These locations can be detected, in a group of gene sequences, as high frequency 'peaks' with respect to a reference position, such as the transcription start site (TSS). We have developed a web tool for the identification of regions containing significant motif peaks. We show, by using different yeast gene datasets, that peak regions are strongly enriched in experimentally-validated motifs and contain potentially important novel motifs. AVAILABILITY: http://genomics.imim.es/peaks |
2005 |
Albà, M Mar, Castresana, Jose Inverse relationship between evolutionary rate and age of mammalian genes. (Article) Molecular biology and evolution, 22 (3), pp. 598–606, 2005, ISSN: 0737-4038. (Abstract | Links | BibTeX | Tags: Animals, DNA, Evolution, Genome, human, Humans, Mice, Molecular, Sequence Analysis) @article{Alba2005, title = {Inverse relationship between evolutionary rate and age of mammalian genes.}, author = {Albà, M Mar and Castresana, Jose}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15537804}, issn = {0737-4038}, year = {2005}, date = {2005-01-01}, journal = {Molecular biology and evolution}, volume = {22}, number = {3}, pages = {598--606}, abstract = {A large number of genes is shared by all living organisms, whereas many others are unique to some specific lineages, indicating their different times of origin. The availability of a growing number of eukaryotic genomes allows us to estimate which mammalian genes are novel genes and, approximately, when they arose. In this article, we classify human genes into four different age groups and estimate evolutionary rates in human and mouse orthologs. We show that older genes tend to evolve more slowly than newer ones; that is, proteins that arose earlier in evolution currently have a larger proportion of sites subjected to negative selection. Interestingly, this property is maintained when a fraction of the fastest-evolving genes is excluded or when only genes belonging to a given functional class are considered. One way to explain this relationship is by assuming that genes maintain their functional constraints along all their evolutionary history, but the nature of more recent evolutionary innovations is such that the functional constraints operating on them are increasingly weaker. Alternatively, our results would also be consistent with a scenario in which the functional constraints acting on a gene would not need to be constant through evolution. Instead, starting from weak functional constraints near the time of origin of a gene-as supported by mechanisms proposed for the origin of orphan genes-there would be a gradual increase in selective pressures with time, resulting in fewer accepted mutations in older versus more novel genes.}, keywords = {Animals, DNA, Evolution, Genome, human, Humans, Mice, Molecular, Sequence Analysis} } A large number of genes is shared by all living organisms, whereas many others are unique to some specific lineages, indicating their different times of origin. The availability of a growing number of eukaryotic genomes allows us to estimate which mammalian genes are novel genes and, approximately, when they arose. In this article, we classify human genes into four different age groups and estimate evolutionary rates in human and mouse orthologs. We show that older genes tend to evolve more slowly than newer ones; that is, proteins that arose earlier in evolution currently have a larger proportion of sites subjected to negative selection. Interestingly, this property is maintained when a fraction of the fastest-evolving genes is excluded or when only genes belonging to a given functional class are considered. One way to explain this relationship is by assuming that genes maintain their functional constraints along all their evolutionary history, but the nature of more recent evolutionary innovations is such that the functional constraints operating on them are increasingly weaker. Alternatively, our results would also be consistent with a scenario in which the functional constraints acting on a gene would not need to be constant through evolution. Instead, starting from weak functional constraints near the time of origin of a gene-as supported by mechanisms proposed for the origin of orphan genes-there would be a gradual increase in selective pressures with time, resulting in fewer accepted mutations in older versus more novel genes. |
2004 |
Gibbs, Richard A, Et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. (Article) Nature, 428 (6982), pp. 493–521, 2004, ISSN: 1476-4687. (Abstract | Links | BibTeX | Tags: Animals, Base Composition, Centromere, Centromere: genetics, Chromosomes, CpG Islands, CpG Islands: genetics, DNA, DNA Transposable Elements, DNA Transposable Elements: genetics, Evolution, Gene Duplication, Genome, Genomics, Humans, Inbred BN, Inbred BN: genetics, Introns, Introns: genetics, Male, Mammalian, Mammalian: genetics, Mice, Mitochondrial, Mitochondrial: genetics, Models, Molecular, Mutagenesis, Nucleic Acid, Nucleic Acid: genetics, Polymorphism, Rats, Regulatory Sequences, Retroelements, Retroelements: genetics, RNA, RNA Splice Sites, RNA Splice Sites: genetics, Sequence Analysis, Single Nucleotide, Single Nucleotide: genetics, Telomere, Telomere: genetics, Untranslated, Untranslated: genetics) @article{Gibbs2004, title = {Genome sequence of the Brown Norway rat yields insights into mammalian evolution.}, author = {Gibbs, Richard A and Et al.}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15057822}, issn = {1476-4687}, year = {2004}, date = {2004-01-01}, journal = {Nature}, volume = {428}, number = {6982}, pages = {493--521}, abstract = {The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.}, keywords = {Animals, Base Composition, Centromere, Centromere: genetics, Chromosomes, CpG Islands, CpG Islands: genetics, DNA, DNA Transposable Elements, DNA Transposable Elements: genetics, Evolution, Gene Duplication, Genome, Genomics, Humans, Inbred BN, Inbred BN: genetics, Introns, Introns: genetics, Male, Mammalian, Mammalian: genetics, Mice, Mitochondrial, Mitochondrial: genetics, Models, Molecular, Mutagenesis, Nucleic Acid, Nucleic Acid: genetics, Polymorphism, Rats, Regulatory Sequences, Retroelements, Retroelements: genetics, RNA, RNA Splice Sites, RNA Splice Sites: genetics, Sequence Analysis, Single Nucleotide, Single Nucleotide: genetics, Telomere, Telomere: genetics, Untranslated, Untranslated: genetics} } The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution. |
2002 |
Messeguer, Xavier, Escudero, Ruth, Farré, Domènec, Núñez, Oscar, Martínez, Javier, Albà, M Mar PROMO: detection of known transcription regulatory elements using species-tailored searches. (Article) Bioinformatics (Oxford, England), 18 (2), pp. 333–4, 2002, ISSN: 1367-4803. (Abstract | Links | BibTeX | Tags: Animals, Binding Sites, Binding Sites: genetics, Computational Biology, DNA, DNA: genetics, DNA: metabolism, Humans, Software, Species Specificity, Transcription Factors, Transcription Factors: metabolism) @article{Messeguer2002, title = {PROMO: detection of known transcription regulatory elements using species-tailored searches.}, author = {Messeguer, Xavier and Escudero, Ruth and Farré, Domènec and Núñez, Oscar and Martínez, Javier and Albà, M Mar}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11847087}, issn = {1367-4803}, year = {2002}, date = {2002-01-01}, journal = {Bioinformatics (Oxford, England)}, volume = {18}, number = {2}, pages = {333--4}, abstract = {We have developed a set of tools to construct positional weight matrices from known transcription factor binding sites in a species or taxon-specific manner, and to search for matches in DNA sequences.}, keywords = {Animals, Binding Sites, Binding Sites: genetics, Computational Biology, DNA, DNA: genetics, DNA: metabolism, Humans, Software, Species Specificity, Transcription Factors, Transcription Factors: metabolism} } We have developed a set of tools to construct positional weight matrices from known transcription factor binding sites in a species or taxon-specific manner, and to search for matches in DNA sequences. |
