This track shows a measure of evolutionary conservation in 6 vertebrates
based on a phylogenetic hidden Markov model, phastCons
(Siepel et al., 2005).
Multiz alignments of the following assemblies were used to generate this
- platypus (Mar. 2007 (WUGSC 5.0.1/ornAna1), ornAna1)
- opossum (Jan. 2006, monDom4)
- human (Mar. 2006, hg18)
- mouse (Feb. 2006, mm8)
- chicken (May 2006, galGal3)
- lizard (Jan. 2007, anoCar1)
Display Conventions and Configuration
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 platypus 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 "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:
- Single line: No bases in the aligned species. Possibly due to a
lineage-specific insertion between the aligned blocks in the platypus genome
or a lineage-specific deletion between the aligned blocks in the aligning
- Double line: Aligning species has one or more unalignable bases in
the gap region. Possibly due to excessive evolutionary distance between
species or independent indels in the region between the aligned blocks in both
- Pale yellow coloring: Aligning species has Ns in the gap region.
Reflects uncertainty in the relationship between the DNA of both species, due
to lack of sequence in relevant portions of the aligning species.
Discontinuities in the genomic context (chromosome, scaffold or region) of the
aligned DNA in the aligning species are shown as follows:
Vertical blue bar: Represents a discontinuity that persists indefinitely
on either side, e.g. a large region of DNA on either side of the bar
comes from a different chromosome in the aligned species due to a large scale
Green square brackets: Enclose shorter alignments consisting of DNA from
one genomic context in the aligned species nested inside a larger chain of
alignments from a different genomic context. The alignment within the
brackets may represent a short misalignment, a lineage-specific insertion of a
transposon in the platypus genome that aligns to a paralogous copy somewhere
else in the aligned species, or other similar occurrence.
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 platypus sequence at those
alignment positions relative to the longest non-platypus 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:
No codon translation: The gene annotation is not used; the bases are
displayed without translation.
Use default species reading frames for translation: The annotations from the genome
in the Default species to establish reading frame pull-down menu are used to
translate all the aligned species present in the alignment.
Use reading frames for species if available, otherwise no translation: Codon
translation is performed only for those species where the region is
annotated as protein coding.
- Use reading frames for species if available, otherwise use default species:
Codon translation is done on those species that are annotated as being protein
coding over the aligned region using species-specific annotation; the remaining
species are translated using the default species annotation.
Codon translation uses the following gene tracks as the basis for
translation, depending on the species chosen (Table 2).
Table 2. Gene tracks used for codon translation.
|Ensembl Genes v62||platypus, chicken|
|Ensembl Genes v60||lizard|
|Ensembl Genes v46||mouse|
|Ensembl Genes v39||opossum|
|UCSC Genes 2009||human|
Best-in-genome pairwise alignments were generated for each species
using lastz, 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
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:
- Alignment tools: lastz (formerly blastz) and multiz by Minmei Hou, Scott Schwartz and Webb
Miller of the Penn State Bioinformatics Group
- Chaining and Netting: axtChain, chainNet by Jim Kent at UCSC
- Conservation scoring: PhastCons, phyloFit, tree_doctor, msa_view by
Adam Siepel while at UCSC, now at Cold Spring Harbor Laboratory
- MAF Annotation tools: mafAddIRows by Brian Raney, UCSC;
genePredToMafFrames by Mark Diekhans, UCSC
- Tree image generator: phyloPng by Galt Barber, UCSC
- Conservation track display: Kate Rosenbloom, Hiram Clawson (wiggle
display), and Brian Raney (gap annotation and codon framing) at UCSC
The phylogenetic tree is based on Murphy et al. (2001) and general
consensus in the vertebrate phylogeny community.
Phylo-HMMs and phastCons:
Felsenstein J, Churchill GA.
A Hidden Markov Model approach to
variation among sites in rate of evolution.
Mol Biol Evol. 1996 Jan;13(1):93-104.
Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K,
Clawson H, Spieth J, Hillier LW, Richards S, et al.
Evolutionarily conserved elements in vertebrate, insect, worm,
and yeast genomes.
Genome Res. 2005 Aug;15(8):1034-50.
PMID: 16024819; PMC: PMC1182216
Siepel A, Haussler D.
Phylogenetic Hidden Markov Models.
In: Nielsen R, editor. Statistical Methods in Molecular Evolution.
New York: Springer; 2005. pp. 325-351.
A space-time process model for the evolution of DNA
Genetics. 1995 Feb;139(2):993-1005.
PMID: 7713447; PMC: PMC1206396
Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D.
duplication, deletion, and rearrangement in the mouse and human genomes.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9.
PMID: 14500911; PMC: PMC208784
Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, Roskin KM,
Baertsch R, Rosenbloom K, Clawson H, Green ED, et al.
Aligning multiple genomic sequences with the threaded blockset aligner.
Genome Res. 2004 Apr;14(4):708-15.
PMID: 15060014; PMC: PMC383317
Lastz (formerly Blastz):
Chiaromonte F, Yap VB, Miller W.
Scoring pairwise genomic sequence alignments.
Pac Symp Biocomput. 2002:115-26.
Improved pairwise alignment of genomic DNA.
Ph.D. Thesis. Pennsylvania State University, USA. 2007.
Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC,
Haussler D, Miller W.
Human-mouse alignments with BLASTZ.
Genome Res. 2003 Jan;13(1):103-7.
PMID: 12529312; PMC: PMC430961
Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E,
Ryder OA, Stanhope MJ, de Jong WW, Springer MS.
Resolution of the early placental mammal radiation using Bayesian phylogenetics.
Science. 2001 Dec 14;294(5550):2348-51.