Description

This track shows basewise measurements of evolutionary conservation/acceleration in particular clades of interest, relative to the levels of conservation/acceleration displayed elsewhere in the phylogeny. These scores were produced by the phyloP program from the PHAST package , using the same species set, multiz alignment, and neutral model of evolution that were used for the main conservation track (see description page for "Vertebrate Multiz Alignment & Conservation (44 Species)" track for details). The individual scores represent -log p-values for a slow-down or speed-up in the estimated evolutionary rate for the clade of interest, relative to the estimated rate outside that clade, under a null hypothesis of neutral evolution (see Methods).

As with the phyloP scores for the main conservation track, positive values indicate a decrease in rate (conservation) and negative values indicate an increase in rate (acceleration). In this case, however, the score measures a change in evolutionary rate in a clade of interest, possibly indicating clade-specific selection rather than the absolute rate across the phylogeny. Note that this track does not attempt to distinguish between negative and positive directional selection. For example, a clade-specific increase in rate could be due to clade-specific positive selection or relaxation of constraint. Similarly, a clade-specific decrease in rate could be due to gain of negative selection or loss of positive selection.

Methods

The scores were produced by running phyloP with the options --method LRT --mode CONACC --wig-scores, and by indicating the clade of interest with the --subtree option (see PHAST docs ). The program was given a neutral model estimated from fourfold degenerate sites, as decribed for the main conservation track. With these options, phyloP performs a likelihood ratio test at each alignment column. This test compares a null model in which the neutral branch lengths are all scaled by a single scaling factor (a free parameter, estimated by maximum likelihood), and an alternative model with separate scaling factors for the clade of interest and the remainder of the phylogeny (both estimated by maximum likelihood). To obtain an approximate p-value, the log likelihood ratio of these two hypotheses is compared to an asymptotic chi-squared null distribution, in the usual way. Scores are then computed as -log 10 p-values. If the estimated rate for the clade of interest is greater than the estimated rate outside that clade, the score is negated, to indicate acceleration rather than conservation.

References

Pollard KS, Salama SR, Lambert N, Lambot M-A, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, and Haussler D. An RNA gene expressed during cortical development evolved rapidly in humans. /Nature/ 443:167-172, 2006.

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.