6 nematode conservation by PhastCons (phastCons6way)
 

Position: chrII:14,646,344-14,667,746

Total Bases in view: 21,403

Statistics on: 19,995 bases (% 93.4215 coverage)

Database: ce6 Table: phastCons6way
Chrom Data
start
Data
end
# of Data
values
Each data
value spans
# bases
Bases
covered
Minimum Maximum Range Mean Variance Standard
deviation
chrII 14646344 14667746 19,995 1 19,995 (93.42%) 0.001 1 0.999 0.648139 0.124308 0.352574

25 bin histogram on 19995 values (zero count bins not shown)
bin
range in bin
minimum maximum
count Relative
Frequency
log2(Frequency)Cumulative
Relative
Frequency
(CRF)
1.0 - CRF
0 0.001 0.04096 1487 0.0743686 -3.74916 0.0743686 0.925631
1 0.04096 0.08092 765 0.0382596 -4.70804 0.112628 0.887372
2 0.08092 0.12088 560 0.028007 -5.15807 0.140635 0.859365
3 0.12088 0.16084 495 0.0247562 -5.33607 0.165391 0.834609
4 0.16084 0.2008 395 0.0197549 -5.66164 0.185146 0.814854
5 0.2008 0.24076 393 0.0196549 -5.66897 0.204801 0.795199
6 0.24076 0.28072 376 0.0188047 -5.73276 0.223606 0.776394
7 0.28072 0.32068 392 0.0196049 -5.67264 0.243211 0.756789
8 0.32068 0.36064 408 0.0204051 -5.61493 0.263616 0.736384
9 0.36064 0.4006 390 0.0195049 -5.68002 0.283121 0.716879
10 0.4006 0.44056 370 0.0185046 -5.75597 0.301625 0.698375
11 0.44056 0.48052 401 0.020055 -5.63989 0.32168 0.67832
12 0.48052 0.52048 414 0.0207052 -5.59386 0.342386 0.657614
13 0.52048 0.56044 579 0.0289572 -5.10993 0.371343 0.628657
14 0.56044 0.6004 506 0.0253063 -5.30436 0.396649 0.603351
15 0.6004 0.64036 412 0.0206052 -5.60085 0.417254 0.582746
16 0.64036 0.68032 412 0.0206052 -5.60085 0.437859 0.562141
17 0.68032 0.72028 445 0.0222556 -5.48969 0.460115 0.539885
18 0.72028 0.76024 440 0.0220055 -5.50599 0.482121 0.517879
19 0.76024 0.8002 473 0.0236559 -5.40166 0.505776 0.494224
20 0.8002 0.84016 535 0.0267567 -5.22396 0.532533 0.467467
21 0.84016 0.88012 616 0.0308077 -5.02057 0.563341 0.436659
22 0.88012 0.92008 920 0.0460115 -4.44186 0.609352 0.390648
23 0.92008 0.96004 1651 0.0825706 -3.59823 0.691923 0.308077
24 0.96004 1 6098 0.304976 -1.71323 0.996899 0.00310078
25 1 1.03996 62 0.00310078 -8.33316 1 0

View table schema

Go to Conservation track controls

Data last updated at UCSC: 2008-06-18

Description

This track shows a measure of evolutionary conservation in C. elegans, C. remanei, C. briggsae, C. brenneri, C. japonica and P. pacificus based on a phylogenetic hidden Markov model, phastCons (Siepel et al., 2005). The multiple alignments were generated using multiz and other tools in the UCSC/Penn State Bioinformatics comparative genomics alignment pipeline. The conservation measurements were created using the phastCons package from Adam Siepel at Cold Spring Harbor Laboratory.

Multiz alignments of the following assemblies were used to generate this track:
OrganismSpeciesRelease date UCSC versionalignment typerepeats masked by
C. elegans (WS190)Caenorhabditis elegans May 2008 (WS190/ce6)ce6reference species repeat masker
C. remaneiCaenorhabditis remanei May 2007caeRem3chain net window masker
C. briggsaeCaenorhabditis briggsae Jan 2007cb3chain net repeat masker
C. brenneriCaenorhabditis brenneri Feb 2008caePb2chain net window masker
C. japonicaCaenorhabditis japonica Mar 2008caeJap1chain net window masker
P. pacificusPristionchus pacificus May 2007priPac1chain net window masker

Table 1. Genome assemblies included in the 9-way Conservation track.

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 C. elegans 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.

Gap Annotation

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 C. elegans genome or a lineage-specific deletion between the aligned blocks in the aligning species.
  • 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 species.
  • 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.

Genomic Breaks

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 rearrangement.
  • 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 C. elegans genome that aligns to a paralogous copy somewhere else in the aligned species, or other similar occurrence.

Base Level

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 C. elegans sequence at those alignment positions relative to the longest non-C. elegans 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 displayed 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:

Gene TrackSpecies
Worm Base Genes (Sanger Genes)C. elegans
C. elegans mapped GenesC. remanei
C. elegans mapped GenesC. briggsae
C. elegans mapped GenesC. brenneri
C. elegans mapped GenesC. japonica
C. elegans mapped GenesP. pacificus

Methods

Pairwise alignments with the C. elegans genome were generated for each species using blastz from repeat-masked or window-masker masked genomic sequence. Pairwise alignments were then linked into chains using a dynamic programming algorithm that finds maximally scoring chains of gapless subsections of the alignments organized in a kd-tree. The scoring matrix and parameters for pairwise alignment and chaining were tuned for each species based on phylogenetic distance from the reference. High-scoring chains were then placed along the genome, with gaps filled by lower-scoring chains, to produce an alignment net. For more information about the chaining and netting process and parameters for each species, see the description pages for the Chain and Net tracks.

The resulting best-in-genome pairwise alignments were progressively aligned using multiz/autoMZ, following the tree topology diagrammed above, to produce multiple alignments. The multiple alignments were post-processed to add annotations indicating alignment gaps, genomic breaks, and base quality of the component sequences. The annotated multiple alignments, in MAF format, are available for bulk download. An alignment summary table containing an entry for each alignment block in each species was generated to improve track display performance at large scales. Framing tables were constructed to enable visualization of codons in the multiple alignment display.

Conservation scoring was performed using the PhastCons package (A. Siepel), which computes conservation based on a two-state phylogenetic hidden Markov model (HMM). PhastCons measurements rely 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 6-way conserved tree model and 6-way non-conserved tree model for this track was constructed from the information in Kiontke et. al. (2005) with the branch length for P. pacificus arbitrarily set manually for the phastCons starting-tree model. The branch lengths in the conserved and non-conserved tree models were produced by the phastCons tuning steps using phyloBoot. The phastCons parameters used for the conservation measurement were: expected-length=15 and target-coverage=0.55

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.

Credits

This track was created at UCSC using the following programs:

  • Alignment tools: 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; mafAddQRows by Richard Burhans, Penn State; 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 Kiontke and Fitch (2005).

References

Phylo-HMM:

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. PMID: 8583911

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.

Yang Z. A space-time process model for the evolution of DNA sequences. Genetics. 1995 Feb;139(2):993-1005. PMID: 7713447; PMC: PMC1206396

Chain/Net:

Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: 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

Multiz:

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

Harris RS. Improved pairwise alignment of genomic DNA. Ph.D. Thesis. Pennsylvania State University, USA. 2007.

Blastz:

Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002;:115-26.c Symp Biocomput. 2002:115-26. PMID: 11928468

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

Phylogenetic Tree:

Kiontke K, Fitch DH. The phylogenetic relationships of Caenorhabditis and other rhabditids. WormBook. 2005 Aug 11:1-11. PMID: 18050394