Description

This track shows measures of evolutionary conservation generated using the phyloP (Phylogenetic P-Values) program from the PHAST package. Two measurements are provided: conservation across 28 species, and an alternative measurement restricted to the placental mammal subset (17 species plus human) of the multiple alignment.

PhyloP differs from phastCons — which is used to produce the scores in the main Conservation track — in several key ways. The scores produced by phyloP reflect individual alignment columns, and do not take into account conservation at neighboring sites. As a result, the phyloP conservation plot has a less smooth appearance, with more "texture" at individual bases, than the phastCons plot. In addition, this property makes phyloP more appropriate than phastCons for evaluating signatures of selection at particular bases or classes of bases in the genome (e.g., all third codon positions). In addition, phyloP requires fewer assumptions than phastCons, by depending only on a model of neutral evolution, rather than on models of both neutral evolution and negative selection (conservation). Finally, rather than representing probabilities of negative selection and ranging between 0 and 1, the phyloP scores represent -log p-values under a null hypothesis of neutral evolution, and range from 0 to infinity (although in practice there is a maximum achievable value for any particular data set).

See the Conservation track description for information about the multiple alignments used as the basis of these conservation measurements.

Display Conventions and Configuration

The track configuration options allow the user to display either the vertebrate or placental mammal conservation scores, or both simultaneously. In full and pack display modes, conservation scores are displayed as a wiggle track in which the height reflects the size of the score. The conservation wiggles can be configured in a variety of ways to highlight different aspects of the displayed information. For example, the windowing function option controls how scores are combined across sites, with averaging as the default. This will have a strong effect on how the plot appears when zoomed out.

Click the Graph configuration help link for an explanation of the configuration options.

Methods

Conservation scoring was performed using the phyloP program from the PHAST package. PhyloP is a general method for computing p-values of conservation by comparing estimated numbers of substitutions along the branches of a phylogeny with the distribution expected under neutral evolution (Siepel, Pollard, and Haussler, 2006). Here it was used to produce separate scores at each base (--wig-scores option), considering all branches of the phylogeny rather than a particular subtree or lineage (i.e., --subtree was not used). Alignment gaps were treated as missing data.

PhyloP relies on a tree model containing the tree topology, branch lengths representing evolutionary distance at neutrally evolving sites, the background distribution of nucleotides, and a substitution rate matrix. The vertebrate tree model for this track was generated using the phyloFit program from the PHAST package (REV model, EM algorithm, medium precision) using multiple alignments of 4-fold degenerate sites extracted from the 28way alignment (msa_view). The 4d sites were derived from the Oct 2005 Gencode Reference Gene set, which was filtered to select single-coverage long transcripts. A second, mammalian tree model including only placental mammals was used to generate the placental mammal conservation scoring.

Credits

This track was created using phyloP, phyloFit, and other programs in PHAST by Adam Siepel's group at Cold Spring Harbor Laboratory (original development done at the Haussler lab at UCSC).

The phylogenetic tree is based on Murphy et al. (2001) and general consensus in the vertebrate phylogeny community as of March 2007.

References

Siepel A, Pollard KS, Haussler D. New methods for detecting lineage-specific selection. Proc. 10th Int'l Conf. on Research in Computational Molecular Biology (RECOMB '06). 2006.

Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, et al. Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science. 14 Dec 2001;294(5550):2348-51.