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. |
2004 |
Huang, Hui, Winter, Eitan E, Wang, Huajun, Weinstock, Keith G, Xing, Heming, Goodstadt, Leo, Stenson, Peter D, Cooper, David N, Smith, Douglas, Albà, M Mar, Ponting, Chris P, Fechtel, Kim Genome biology, 5 (7), pp. R47, 2004, ISSN: 1465-6914. (Abstract | Links | BibTeX | Tags: 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{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} } 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. |
