This track shows a multiple alignment of 447 mammalian genomes made with Cactus and constraint scores derived from it.
To build this track, the Zoonomia 241 alignment was used as a starting point, all primates and a few outdated
assemblies were removed and an alignment between 233 newly sequenced primates was added. See the Methods section below for details, and
also the publications by Kuderna et al. 2023 in the Reference section.
All alignments and operations on them were performed using the Cactus toolkit.
This track shows four phyloP conservation score subtracks computed from the
447-way Cactus alignment (and a primates subset of it):
447 phyloP REV: all 447 species, REV substitution model.
447 phyloP primates LRT: 233 primates subset, likelihood-ratio
test scoring.
The SSREV substitution model is strand-symmetric, which avoids
strand-dependent bias in single-base conservation scores (Pollard
et al. 2010, supplementary section 2.4) -- relevant when analyzing
transcript-related nucleotides such as splice sites, miRNA seed regions, or
other strand-specific sequence features. The REV model is the standard
phyloP model and is appropriate for general genome-wide conservation
analysis. The primates subset tracks restrict scoring to the 233 primate
genomes included in the alignment, useful when conservation across
non-primate mammals would dilute primate-specific signal.
Data Access
Downloads for data in this track are available from the directory:
In full and pack display modes, conservation scores are displayed as a
wiggle track (histogram) 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.
Click the Graph configuration help link for an explanation
of the configuration options.
Pairwise alignments of each species to the human genome are
displayed below the conservation histogram 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.
Checkboxes on the track configuration page allow selection of the
species to include in the pairwise display.
Note that excluding species from the pairwise display does not alter the
conservation score display.
To view detailed information about the alignments at a specific
position, zoom the display in 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. Missing sequence in any
assembly is highlighted in the track display by regions of yellow when zoomed
out and by Ns when displayed at base level. 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 human 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 human 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 human sequence at those
alignment positions relative to the longest non-human sequence.
If there is sufficient space in the display, the size of the gap is shown.
If the space is insufficient and the gap size is a multiple of 3, a
"*" is displayed; other gap sizes are indicated by "+".
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:
One additional cat genome, "Felis_catus_fca126" (GCA_018350175.1) was
added as a sister taxa to the existing "Felis_catus" species
Five additional canine genomes were also added: canFam4,
"Canis_lupus_dingo" (GCA_003254725.1), "Canis_lupus_orion"
(GCA_905319855.2), "Nyctereutes_procyonoides" (GCA_905146905.1) and
"Otocyon_megalotis" (GCA_017311455.1). "Canis_lupus" from the Zoonomia
alignment was also renamed "Canis_lupus_VD" to reflect the fact that it
corresponds to a "village dog" and not "wolf" sample.
phyloP scores were computed from the Cactus 447-way alignment using the
phyloP program from the
PHAST package.
Per-base scores were produced with options
--method LRT --mode CONACC --wig-scores; positive scores
indicate conservation under purifying selection, negative scores indicate
acceleration relative to neutral evolution.
For the all-species tracks, base-composition and substitution-rate
parameters were estimated from 4-fold degenerate sites using
phyloFit (PHAST, EM algorithm, medium precision) under either the
REV or strand-symmetric reversible (SSREV) substitution model. Background
base frequencies were adjusted with modFreqs so that
complementary bases (A/T and C/G) appear at equal expected frequencies,
which is required for strand-symmetric scoring.
For the primates-subset tracks, the alignment was restricted to the 233
primate species and an independent phyloFit / phyloP run was performed on
that sub-alignment using the SSREV model. All scores were encoded into
wiggle format and loaded as either bigWig files (REV all-species,
primates LRT) or wig SQL tables backed by .wib data files
(SSREV all-species, SSREV primates).