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Human PAML browser: a database of positive selection on human genes using phylogenetic methods.

Nickel GC, Tefft D, Adams MD - Nucleic Acids Res. (2007)

Bottom Line: Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species.Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage.However, the ML methods are computationally intensive and awkward to configure.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH, USA.

ABSTRACT
With the recent increase in the number of mammalian genomes being sequenced, large-scale genome scans for human-specific positive selection are now possible. Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species. Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage. However, the ML methods are computationally intensive and awkward to configure. We have created a database that contains the results of tests for positive selection along the human lineage in 13,721 genes with orthologs in the UCSC multispecies genome alignments. The Human PAML Browser is a resource through which researchers can search for a gene of interest or groups of genes by Gene Ontology category, and obtain coding sequence alignments for the gene and as well as results from tests of positive selection from the software package Phylogenetic Analysis by Maximum Likelihood. The Human PAML Browser is available at http://mendel.gene.cwru.edu/adamslab/pbrowser.py.

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Likelihood test data and results for IRX3. (A) Branch tests for selection, Model H (test model) and Model H (neutral model). The variables in the table are as follows: t, the length of the branch; s and n, the number of synonymous and non-synonymous sites, respectively; dN/dS, the ratio of the rate of non-synonymous and synonymous substitution for the branch; dN and dS, the rate of synonymous and non-synonymous substitution on the branch; S*dS and N*dN, a rough estimate of the absolute number of synonymous and non-synonymous substitutions. (B) Branch + site tests for selection, including the proportion of codons in each site class for the background and foreground (human) lineage, and the posterior probability that a given site is positively selected.
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Figure 4: Likelihood test data and results for IRX3. (A) Branch tests for selection, Model H (test model) and Model H (neutral model). The variables in the table are as follows: t, the length of the branch; s and n, the number of synonymous and non-synonymous sites, respectively; dN/dS, the ratio of the rate of non-synonymous and synonymous substitution for the branch; dN and dS, the rate of synonymous and non-synonymous substitution on the branch; S*dS and N*dN, a rough estimate of the absolute number of synonymous and non-synonymous substitutions. (B) Branch + site tests for selection, including the proportion of codons in each site class for the background and foreground (human) lineage, and the posterior probability that a given site is positively selected.

Mentions: Multispecies protein alignment for IRX3. Coding sequence was extracted from whole-genome sequence alignments available from the UCSC Genome Browser and trimmed to include only coding regions based on matches with the human CDS. Alignment columns with gaps in the human sequence were excluded. Residues 1–180 of 501 are shown. Residues 36 and 44 were predicted to be positively selected in human with Bayes Empirical Bayes posterior probability of 0.886 and 0.997, respectively (Figure 4B).


Human PAML browser: a database of positive selection on human genes using phylogenetic methods.

Nickel GC, Tefft D, Adams MD - Nucleic Acids Res. (2007)

Likelihood test data and results for IRX3. (A) Branch tests for selection, Model H (test model) and Model H (neutral model). The variables in the table are as follows: t, the length of the branch; s and n, the number of synonymous and non-synonymous sites, respectively; dN/dS, the ratio of the rate of non-synonymous and synonymous substitution for the branch; dN and dS, the rate of synonymous and non-synonymous substitution on the branch; S*dS and N*dN, a rough estimate of the absolute number of synonymous and non-synonymous substitutions. (B) Branch + site tests for selection, including the proportion of codons in each site class for the background and foreground (human) lineage, and the posterior probability that a given site is positively selected.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2238824&req=5

Figure 4: Likelihood test data and results for IRX3. (A) Branch tests for selection, Model H (test model) and Model H (neutral model). The variables in the table are as follows: t, the length of the branch; s and n, the number of synonymous and non-synonymous sites, respectively; dN/dS, the ratio of the rate of non-synonymous and synonymous substitution for the branch; dN and dS, the rate of synonymous and non-synonymous substitution on the branch; S*dS and N*dN, a rough estimate of the absolute number of synonymous and non-synonymous substitutions. (B) Branch + site tests for selection, including the proportion of codons in each site class for the background and foreground (human) lineage, and the posterior probability that a given site is positively selected.
Mentions: Multispecies protein alignment for IRX3. Coding sequence was extracted from whole-genome sequence alignments available from the UCSC Genome Browser and trimmed to include only coding regions based on matches with the human CDS. Alignment columns with gaps in the human sequence were excluded. Residues 1–180 of 501 are shown. Residues 36 and 44 were predicted to be positively selected in human with Bayes Empirical Bayes posterior probability of 0.886 and 0.997, respectively (Figure 4B).

Bottom Line: Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species.Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage.However, the ML methods are computationally intensive and awkward to configure.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH, USA.

ABSTRACT
With the recent increase in the number of mammalian genomes being sequenced, large-scale genome scans for human-specific positive selection are now possible. Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species. Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage. However, the ML methods are computationally intensive and awkward to configure. We have created a database that contains the results of tests for positive selection along the human lineage in 13,721 genes with orthologs in the UCSC multispecies genome alignments. The Human PAML Browser is a resource through which researchers can search for a gene of interest or groups of genes by Gene Ontology category, and obtain coding sequence alignments for the gene and as well as results from tests of positive selection from the software package Phylogenetic Analysis by Maximum Likelihood. The Human PAML Browser is available at http://mendel.gene.cwru.edu/adamslab/pbrowser.py.

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