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
2012 |
Toll-Riera, Macarena, Bostick, David, Albà, M Mar, Plotkin, Joshua B Structure and age jointly influence rates of protein evolution. (Article) PLoS computational biology, 8 (5), pp. e1002542, 2012, ISSN: 1553-7358. (Abstract | Links | BibTeX | Tags: Animals, Binding Sites, Computational Biology, Eukaryota, Evolution, Humans, Mice, Molecular, Protein Conformation, Protein Stability, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: metabolism, Solvents) @article{Toll-Riera2012a, title = {Structure and age jointly influence rates of protein evolution.}, author = {Toll-Riera, Macarena and Bostick, David and Albà, M Mar and Plotkin, Joshua B}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3364943&tool=pmcentrez&rendertype=abstract}, issn = {1553-7358}, year = {2012}, date = {2012-01-01}, journal = {PLoS computational biology}, volume = {8}, number = {5}, pages = {e1002542}, abstract = {What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate. We use a large set of one-to-one orthologs between human and mouse proteins, with mapped PDB structures. We report that previously observed structural correlations also hold within each age group - including relationships between solvent accessibility, designabililty, and evolutionary rates. However, age also plays a crucial role: age modulates the relationship between solvent accessibility and rate. Additionally, younger proteins, despite being less designable, tend to evolve faster than older proteins. We show that previously reported relationships between age and rate cannot be explained by structural biases among age groups. Finally, we introduce a knowledge-based potential function to study the stability of proteins through large-scale computation. We find that older proteins are more stable for their native structure, and more robust to mutations, than younger ones. Our results underscore that several determinants, both intrinsic and historical, can interact to determine rates of protein evolution.}, keywords = {Animals, Binding Sites, Computational Biology, Eukaryota, Evolution, Humans, Mice, Molecular, Protein Conformation, Protein Stability, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: metabolism, Solvents} } What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate. We use a large set of one-to-one orthologs between human and mouse proteins, with mapped PDB structures. We report that previously observed structural correlations also hold within each age group - including relationships between solvent accessibility, designabililty, and evolutionary rates. However, age also plays a crucial role: age modulates the relationship between solvent accessibility and rate. Additionally, younger proteins, despite being less designable, tend to evolve faster than older proteins. We show that previously reported relationships between age and rate cannot be explained by structural biases among age groups. Finally, we introduce a knowledge-based potential function to study the stability of proteins through large-scale computation. We find that older proteins are more stable for their native structure, and more robust to mutations, than younger ones. Our results underscore that several determinants, both intrinsic and historical, can interact to determine rates of protein evolution. |
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. |
