Amino Acid Animals Computational Biology Databases de novo gene DNA Evolution Genetic Genome Humans lncRNA Mice Molecular Molecular Sequence Data Nucleic Acid Proteins Proteins: chemistry Proteins: genetics Repetitive Sequences ribosome profiling RNA-Seq Sequence Analysis Sequence Homology transcriptomics yeast
2011 |
Toll-Riera, Macarena, Laurie, Steve, Albà, M Mar Lineage-specific variation in intensity of natural selection in mammals. (Article) Molecular biology and evolution, 28 (1), pp. 383–98, 2011, ISSN: 1537-1719. (Abstract | Links | BibTeX | Tags: Amino Acid Sequence, Amino Acid Substitution, Animals, Evolution, F-Box Proteins, F-Box Proteins: genetics, G-Protein-Coupled, G-Protein-Coupled: genetics, Genetic, Genetic Variation, Humans, Mammals, Mammals: genetics, Molecular, Molecular Sequence Data, N-Methyl-D-Aspartate, N-Methyl-D-Aspartate: genetics, Odorant, Odorant: genetics, Receptors, Selection, Sequence Alignment) @article{Toll-Riera2011a, title = {Lineage-specific variation in intensity of natural selection in mammals.}, author = {Toll-Riera, Macarena and Laurie, Steve and Albà, M Mar}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20688808}, issn = {1537-1719}, year = {2011}, date = {2011-01-01}, journal = {Molecular biology and evolution}, volume = {28}, number = {1}, pages = {383--98}, abstract = {The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here, we present a method to identify such deviations and apply it to a data set of 2,929 high-quality coding sequence alignments corresponding to one-to-one orthologous genes from six mammalian species--human, macaque, mouse, rat, cow, and dog. Deviated branches are defined as those that present significant alterations in both the rate of nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well-conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection (PS) tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify PS in accelerated branches with an excess of radical amino acid replacements suggests that these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by PS tests. We discuss in detail several examples of genes that show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception, and ubiquitination.}, keywords = {Amino Acid Sequence, Amino Acid Substitution, Animals, Evolution, F-Box Proteins, F-Box Proteins: genetics, G-Protein-Coupled, G-Protein-Coupled: genetics, Genetic, Genetic Variation, Humans, Mammals, Mammals: genetics, Molecular, Molecular Sequence Data, N-Methyl-D-Aspartate, N-Methyl-D-Aspartate: genetics, Odorant, Odorant: genetics, Receptors, Selection, Sequence Alignment} } The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here, we present a method to identify such deviations and apply it to a data set of 2,929 high-quality coding sequence alignments corresponding to one-to-one orthologous genes from six mammalian species--human, macaque, mouse, rat, cow, and dog. Deviated branches are defined as those that present significant alterations in both the rate of nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well-conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection (PS) tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify PS in accelerated branches with an excess of radical amino acid replacements suggests that these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by PS tests. We discuss in detail several examples of genes that show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception, and ubiquitination. |
2009 |
Salichs, Eulàlia, Ledda, Alice, Mularoni, Loris, Albà, M Mar, de la Luna, Susana PLoS genetics, 5 (3), pp. e1000397, 2009, ISSN: 1553-7404. (Abstract | Links | BibTeX | Tags: Amino Acids, Cell Line, Cell Nucleus, Cell Nucleus: chemistry, Cell Nucleus: genetics, Cell Nucleus: metabolism, Genome, Histidine, Histidine: chemistry, Histidine: genetics, Histidine: metabolism, human, Humans, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins, Nuclear Proteins: chemistry, Nuclear Proteins: genetics, Nuclear Proteins: metabolism, Protein Transport, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: metabolism, Sequence Alignment, Tandem Repeat Sequences) @article{Salichs2009, title = {Genome-wide analysis of histidine repeats reveals their role in the localization of human proteins to the nuclear speckles compartment.}, author = {Salichs, Eulàlia and Ledda, Alice and Mularoni, Loris and Albà, M Mar and de la Luna, Susana}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2644819&tool=pmcentrez&rendertype=abstract}, issn = {1553-7404}, year = {2009}, date = {2009-01-01}, journal = {PLoS genetics}, volume = {5}, number = {3}, pages = {e1000397}, abstract = {Single amino acid repeats are prevalent in eukaryote organisms, although the role of many such sequences is still poorly understood. We have performed a comprehensive analysis of the proteins containing homopolymeric histidine tracts in the human genome and identified 86 human proteins that contain stretches of five or more histidines. Most of them are endowed with DNA- and RNA-related functions, and, in addition, there is an overrepresentation of proteins expressed in the brain and/or nervous system development. An analysis of their subcellular localization shows that 15 of the 22 nuclear proteins identified accumulate in the nuclear subcompartment known as nuclear speckles. This localization is lost when the histidine repeat is deleted, and significantly, closely related paralogous proteins without histidine repeats also fail to localize to nuclear speckles. Hence, the histidine tract appears to be directly involved in targeting proteins to this compartment. The removal of DNA-binding domains or treatment with RNA polymerase II inhibitors induces the re-localization of several polyhistidine-containing proteins from the nucleoplasm to nuclear speckles. These findings highlight the dynamic relationship between sites of transcription and nuclear speckles. Therefore, we define the histidine repeats as a novel targeting signal for nuclear speckles, and we suggest that these repeats are a way of generating evolutionary diversification in gene duplicates. These data contribute to our better understanding of the physiological role of single amino acid repeats in proteins.}, keywords = {Amino Acids, Cell Line, Cell Nucleus, Cell Nucleus: chemistry, Cell Nucleus: genetics, Cell Nucleus: metabolism, Genome, Histidine, Histidine: chemistry, Histidine: genetics, Histidine: metabolism, human, Humans, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins, Nuclear Proteins: chemistry, Nuclear Proteins: genetics, Nuclear Proteins: metabolism, Protein Transport, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: metabolism, Sequence Alignment, Tandem Repeat Sequences} } Single amino acid repeats are prevalent in eukaryote organisms, although the role of many such sequences is still poorly understood. We have performed a comprehensive analysis of the proteins containing homopolymeric histidine tracts in the human genome and identified 86 human proteins that contain stretches of five or more histidines. Most of them are endowed with DNA- and RNA-related functions, and, in addition, there is an overrepresentation of proteins expressed in the brain and/or nervous system development. An analysis of their subcellular localization shows that 15 of the 22 nuclear proteins identified accumulate in the nuclear subcompartment known as nuclear speckles. This localization is lost when the histidine repeat is deleted, and significantly, closely related paralogous proteins without histidine repeats also fail to localize to nuclear speckles. Hence, the histidine tract appears to be directly involved in targeting proteins to this compartment. The removal of DNA-binding domains or treatment with RNA polymerase II inhibitors induces the re-localization of several polyhistidine-containing proteins from the nucleoplasm to nuclear speckles. These findings highlight the dynamic relationship between sites of transcription and nuclear speckles. Therefore, we define the histidine repeats as a novel targeting signal for nuclear speckles, and we suggest that these repeats are a way of generating evolutionary diversification in gene duplicates. These data contribute to our better understanding of the physiological role of single amino acid repeats in proteins. |
2007 |
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 |
