This track shows a measure of evolutionary conservation in 9 vertebrates, including mammalian, amphibian, bird, and fish species, based on a phylogenetic hidden Markov model, phastCons (Siepel et al., 2005). Multiz alignments of the following assemblies were used to generate this track:
In full and pack display modes, conservation scores are displayed as a "wiggle" (histogram), where the height reflects the size of the score. Pairwise alignments of each species to the $organism genome are displayed below as a grayscale density plot (in pack mode) or as a "wiggle" (in full mode) that indicates alignment quality. In dense display mode, conservation is shown in grayscale using darker values to indicate higher levels of overall conservation as scored by phastCons.
The conservation wiggle can be configured in a variety of ways to highlight different aspects of the displayed information. Click the Graph configuration help link for an explanation of the configuration options.
Checkboxes in the track configuration section allow excluding species from the pairwise display; however, this does not remove them from the conservation score display. To view detailed information about the alignments at a specific position, zoom in the display to 30,000 or fewer bases, then click on the alignment.
The "Display chains between alignments" configuration option enables display of gaps between alignment blocks in the pairwise alignments in a manner similar to the Chain track display. The following conventions are used:
Discontinuities in the genomic context (chromosome, scaffold or region) of the aligned DNA in the aligning species are shown as follows:
When zoomed-in to the base-level display, the track shows the base composition of each alignment. The numbers and symbols on the Gaps line indicate the lengths of gaps in the $organism sequence at those alignment positions relative to the longest non-$organism sequence. If there is sufficient space in the display, the size of the gap is shown; if not, and if the gap size is a multiple of 3, a "*" is displayed, otherwise "+" is shown.
Codon translation is available in base-level display mode if the displayed region is identified as a coding segment. To display this annotation, select the species for translation from the pull-down menu in the Codon Translation configuration section at the top of the page. Then, select one of the following modes:
Codon translation uses the following gene tracks as the basis for translation, depending on the species chosen:
Gene Track Species Known Genes rat, mouse, human RefSeq Genes chicken MGC Genes X. tropicalis mRNAs dog, cow, zebrafish not translated opossum
Best-in-genome pairwise alignments were generated for each species using blastz, followed by chaining and netting. The pairwise alignments were then multiply aligned using multiz, following the ordering of the species tree diagrammed above. The resulting multiple alignments were then assigned conservation scores by phastCons, using a tree model with branch lengths derived from the ENCODE project Multi-Species Sequence Analysis group, September 2005 tree model. This tree was generated from TBA alignments over 23 vertebrate species and is based on 4D sites.
The phastCons program computes conservation scores based on a phylo-HMM, a type of probabilistic model that describes both the process of DNA substitution at each site in a genome and the way this process changes from one site to the next (Felsenstein and Churchill 1996, Yang 1995, Siepel and Haussler 2005). PhastCons uses a two-state phylo-HMM, with a state for conserved regions and a state for non-conserved regions. The value plotted at each site is the posterior probability that the corresponding alignment column was "generated" by the conserved state of the phylo-HMM. These scores reflect the phylogeny (including branch lengths) of the species in question, a continuous-time Markov model of the nucleotide substitution process, and a tendency for conservation levels to be autocorrelated along the genome (i.e., to be similar at adjacent sites). The general reversible (REV) substitution model was used. Note that, unlike many conservation-scoring programs, phastCons does not rely on a sliding window of fixed size, so short highly-conserved regions and long moderately conserved regions can both obtain high scores. More information about phastCons can be found in Siepel et al. (2005).
PhastCons currently treats alignment gaps as missing data, which sometimes has the effect of producing undesirably high conservation scores in gappy regions of the alignment. We are looking at several possible ways of improving the handling of alignment gaps.
This track was created using the following programs:
The phylogenetic tree is based on Murphy et al. (2001) and general consensus in the vertebrate phylogeny community.
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