Downloads for data in this track are available:
This track shows multiple alignments of 100 vertebrate species and measurements of evolutionary conservation using two methods (phastCons and phyloP) from the PHAST package, for all species. The multiple alignments were generated using multiz and other tools in the UCSC/Penn State Bioinformatics comparative genomics alignment pipeline. Conserved elements identified by phastCons are also displayed in this track.
PhastCons is a hidden Markov model-based method that estimates the probability that each nucleotide belongs to a conserved element, based on the multiple alignment. It considers not just each individual alignment column, but also its flanking columns. By contrast, phyloP separately measures conservation at individual columns, ignoring the effects of their neighbors. As a consequence, the phyloP plots have a less smooth appearance than the phastCons plots, with more "texture" at individual sites. The two methods have different strengths and weaknesses. PhastCons is sensitive to "runs" of conserved sites, and is therefore effective for picking out conserved elements. PhyloP, on the other hand, is more appropriate for evaluating signatures of selection at particular nucleotides or classes of nucleotides (e.g., third codon positions, or first positions of miRNA target sites).
Another important difference is that phyloP can measure acceleration (faster evolution than expected under neutral drift) as well as conservation (slower than expected evolution). In the phyloP plots, sites predicted to be conserved are assigned positive scores (and shown in blue), while sites predicted to be fast-evolving are assigned negative scores (and shown in red). The absolute values of the scores represent -log p-values under a null hypothesis of neutral evolution. The phastCons scores, by contrast, represent probabilities of negative selection and range between 0 and 1.
Both phastCons and phyloP treat alignment gaps and unaligned nucleotides as missing data, and both were run with the same parameters.
UCSC has repeatmasked and aligned all genome assemblies, and provides all the sequences for download. For genome assemblies not available in the genome browser, there are alternative assembly hub genome browsers. 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 (see Gap Annotation, below).
Primate subset Organism Species Release date UCSC version Alignment type Baboon Papio hamadryas Mar 2012 Baylor Panu_2.0/papAnu2 Reciprocal best net Bushbaby Otolemur garnettii Mar 2011 Broad/otoGar3 Syntenic net Chimp Pan troglodytes Feb 2011 CSAC 2.1.4/panTro4 Syntenic net Crab-eating macaque Macaca fascicularis Jun 2013 Macaca_fascicularis_5.0/macFas5 Syntenic net Gibbon Nomascus leucogenys Oct 2012 GGSC Nleu3.0/nomLeu3 Syntenic net Gorilla Gorilla gorilla gorilla May 2011 gorGor3.1/gorGor3 Reciprocal best net Green monkey Chlorocebus sabaeus Mar 2014 Chlorocebus_sabeus 1.1/chlSab2 Syntenic net Human Homo sapiens Dec 2013 GRCh38/hg38 reference species Marmoset Callithrix jacchus Mar 2009 WUGSC 3.2/calJac3 Syntenic net Orangutan Pongo pygmaeus abelii July 2007 WUGSC 2.0.2/ponAbe2 Reciprocal best net Rhesus Macaca mulatta Oct 2010 BGI CR_1.0/rheMac3 Syntenic net Squirrel monkey Saimiri boliviensis Oct 2011 Broad/saiBol1 Syntenic net Euarchontoglires subset Brush-tailed rat Octodon degus Apr 2012 OctDeg1.0/octDeg1 Syntenic net Chinchilla Chinchilla lanigera May 2012 ChiLan1.0/chiLan1 Syntenic net Chinese hamster Cricetulus griseus Jul 2013 C_griseus_v1.0/criGri1 Syntenic net Chinese tree shrew Tupaia chinensis Jan 2013 TupChi_1.0/tupChi1 Syntenic net Golden hamster Mesocricetus auratus Mar 2013 MesAur1.0/mesAur1 Syntenic net Guinea pig Cavia porcellus Feb 2008 Broad/cavPor3 Syntenic net Lesser Egyptian jerboa Jaculus jaculus May 2012 JacJac1.0/jacJac1 Syntenic net Mouse Mus musculus Dec 2011 GRCm38/mm10 Syntenic net Naked mole-rat Heterocephalus glaber Jan 2012 Broad HetGla_female_1.0/hetGla2 Syntenic net Pika Ochotona princeps May 2012 OchPri3.0/ochPri3 Syntenic net Prairie vole Microtus ochrogaster Oct 2012 MicOch1.0/micOch1 Syntenic net Rabbit Oryctolagus cuniculus Apr 2009 Broad/oryCun2 Syntenic net Rat Rattus norvegicus Jul 2014 RGSC 6.0/rn6 Syntenic net Squirrel Spermophilus tridecemlineatus Nov 2011 Broad/speTri2 Syntenic net Laurasiatheria subset Alpaca Vicugna pacos Mar 2013 Vicugna_pacos-2.0.1/vicPac2 Syntenic net Bactrian camel Camelus ferus Dec 2011 CB1/camFer1 Syntenic net Big brown bat Eptesicus fuscus Jul 2012 EptFus1.0/eptFus1 Syntenic net Black flying-fox Pteropus alecto Aug 2012 ASM32557v1/pteAle1 Syntenic net Cat Felis catus Nov 2014 ICGSC Felis_catus 8.0/felCat8 Syntenic net Cow Bos taurus Jun 2014 Bos_taurus_UMD_3.1.1/bosTau8 Syntenic net David's myotis bat Myotis davidii Aug 2012 ASM32734v1/myoDav1 Syntenic net Dog Canis lupus familiaris Sep 2011 Broad CanFam3.1/canFam3 Syntenic net Dolphin Tursiops truncatus Oct 2011 Baylor Ttru_1.4/turTru2 Reciprocal best net Domestic goat Capra hircus May 2012 CHIR_1.0/capHir1 Syntenic net Ferret Mustela putorius furo Apr 2011 MusPutFur1.0/musFur1 Syntenic net Hedgehog Erinaceus europaeus May 2012 EriEur2.0/eriEur2 Syntenic net Horse Equus caballus Sep 2007 Broad/equCab2 Syntenic net Killer whale Orcinus orca Jan 2013 Oorc_1.1/orcOrc1 Syntenic net Megabat Pteropus vampyrus Jul 2008 Broad/pteVam1 Reciprocal best net Microbat Myotis lucifugus Jul 2010 Broad Institute Myoluc2.0/myoLuc2 Syntenic net Pacific walrus Odobenus rosmarus divergens Jan 2013 Oros_1.0/odoRosDiv1 Syntenic net Panda Ailuropoda melanoleuca Dec 2009 BGI-Shenzhen 1.0/ailMel1 Syntenic net Pig Sus scrofa Aug 2011 SGSC Sscrofa10.2/susScr3 Syntenic net Sheep Ovis aries Aug 2012 ISGC Oar_v3.1/oviAri3 Syntenic net Shrew Sorex araneus Aug 2008 Broad/sorAra2 Syntenic net Star-nosed mole Condylura cristata Mar 2012 ConCri1.0/conCri1 Syntenic net Tibetan antelope Pantholops hodgsonii May 2013 PHO1.0/panHod1 Syntenic net Weddell seal Leptonychotes weddellii Mar 2013 LepWed1.0/lepWed1 Reciprocal best net White rhinoceros Ceratotherium simum May 2012 CerSimSim1.0/cerSim1 Syntenic net Afrotheria subset Aardvark Orycteropus afer afer May 2012 OryAfe1.0/oryAfe1 Syntenic net Cape elephant shrew Elephantulus edwardii Aug 2012 EleEdw1.0/eleEdw1 Syntenic net Cape golden mole Chrysochloris asiatica Aug 2012 ChrAsi1.0/chrAsi1 Syntenic net Elephant Loxodonta africana Jul 2009 Broad/loxAfr3 Syntenic net Manatee Trichechus manatus latirostris Oct 2011 Broad v1.0/triMan1 Syntenic net Tenrec Echinops telfairi Nov 2012 Broad/echTel2 Syntenic net Mammal subset Armadillo Dasypus novemcinctus Dec 2011 Baylor/dasNov3 Syntenic net Opossum Monodelphis domestica Oct 2006 Broad/monDom5 Net Platypus Ornithorhynchus anatinus Mar 2007 WUGSC 5.0.1/ornAna1 Reciprocal best net Tasmanian devil Sarcophilus harrisii Feb 2011 WTSI Devil_ref v7.0/sarHar1 Net Wallaby Macropus eugenii Sep 2009 TWGS Meug_1.1/macEug2 Reciprocal best net Aves subset Budgerigar Melopsittacus undulatus Sep 2011 WUSTL v6.3/melUnd1 Net Chicken Gallus gallus Nov 2011 ICGSC Gallus_gallus-4.0/galGal4 Net Collared flycatcher Ficedula albicollis Jun 2013 FicAlb1.5/ficAlb2 Net Mallard duck Anas platyrhynchos Apr 2013 BGI_duck_1.0/anaPla1 Net Medium ground finch Geospiza fortis Apr 2012 GeoFor_1.0/geoFor1 Net Parrot Amazona vittata Jan 2013 AV1/amaVit1 Net Peregrine falcon Falco peregrinus Feb 2013 F_peregrinus_v1.0/falPer1 Net Rock pigeon Columba livia Feb 2013 Cliv_1.0/colLiv1 Net Saker falcon Falco cherrug Feb 2013 F_cherrug_v1.0/falChe1 Net Scarlet macaw Ara macao Jun 2013 SMACv1.1/araMac1 Net Tibetan ground jay Pseudopodoces humilis Jan 2013 PseHum1.0/pseHum1 Net Turkey Meleagris gallopavo Dec 2009 TGC Turkey_2.01/melGal1 Net White-throated sparrow Zonotrichia albicollis Apr 2013 ASM38545v1/zonAlb1 Net Zebra finch Taeniopygia guttata Feb 2013 WashU taeGut324/taeGut2 Net Sarcopterygii subset American alligator Alligator mississippiensis Aug 2012 allMis0.2/allMis1 Net Chinese softshell turtle Pelodiscus sinensis Oct 2011 PelSin_1.0/pelSin1 Net Coelacanth Latimeria chalumnae Aug 2011 Broad/latCha1 Net Green seaturtle Chelonia mydas Mar 2013 CheMyd_1.0/cheMyd1 Net Lizard Anolis carolinensis May 2010 Broad AnoCar2.0/anoCar2 Net Painted turtle Chrysemys picta bellii Mar 2014 v3.0.3/chrPic2 Net Spiny softshell turtle Apalone spinifera May 2013 ASM38561v1/apaSpi1 Net X. tropicalis Xenopus tropicalis Sep 2012 JGI 7.0/xenTro7 Net Fish subset Atlantic cod Gadus morhua May 2010 Genofisk GadMor_May2010/gadMor1 Net Burton's mouthbreeder Haplochromis burtoni Oct 2011 AstBur1.0/hapBur1 Net Fugu Takifugu rubripes Oct 2011 FUGU5/fr3 Net Lamprey Petromyzon marinus Sep 2010 WUGSC 7.0/petMar2 Net Medaka Oryzias latipes Oct 2005 NIG/UT MEDAKA1/oryLat2 Net Mexican tetra (cavefish) Astyanax mexicanus Apr 2013 Astyanax_mexicanus-1.0.2/astMex1 Net Nile tilapia Oreochromis niloticus Jan 2011 Broad oreNil1.1/oreNil2 Net Princess of Burundi Neolamprologus brichardi May 2011 NeoBri1.0/neoBri1 Net Pundamilia nyererei Pundamilia nyererei Oct 2011 PunNye1.0/punNye1 Net Southern platyfish Xiphophorus maculatus Jan 2012 Xiphophorus_maculatus-4.4.2/xipMac1 Net Spotted gar Lepisosteus oculatus Dec 2011 LepOcu1/lepOcu1 Net Stickleback Gasterosteus aculeatus Feb 2006 Broad/gasAcu1 Net Tetraodon Tetraodon nigroviridis Mar 2007 Genoscope 8.0/tetNig2 Net Yellowbelly pufferfish Takifugu flavidus May 2013 version 1 of Takifugu flavidus genome/takFla1 Net Zebra mbuna Maylandia zebra Mar 2012 MetZeb1.1/mayZeb1 Net Zebrafish Danio rerio Sep 2014 GRCz10/danRer10 Net
Table 1. Genome assemblies included in the 100-way Conservation track.
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 $organism 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 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.
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 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:
Codon translation uses the following gene tracks as the basis for translation:
Table 2. Gene tracks used for codon translation.
Gene Track Species UCSC Genes Human, Mouse RefSeq Genes Cow, Frog (X. tropicalis) Ensembl Genes v73 Atlantic cod, Bushbaby, Cat, Chicken, Chimp, Coelacanth, Dog, Elephant, Ferret, Fugu, Gorilla, Horse, Lamprey, Lizard, Mallard duck, Marmoset, Medaka, Megabat, Microbat, Orangutan, Panda, Pig, Platypus, Rat, Soft-shell Turtle, Southern platyfish, Squirrel, Tasmanian devil, Tetraodon, Zebrafish no annotation Aardvark, Alpaca, American alligator, Armadillo, Baboon, Bactrian camel, Big brown bat, Black flying-fox, Brush-tailed rat, Budgerigar, Burton's mouthbreeder, Cape elephant shrew, Cape golden mole, Chinchilla, Chinese hamster, Chinese tree shrew, Collared flycatcher, Crab-eating macaque, David's myotis (bat), Dolphin, Domestic goat, Gibbon, Golden hamster, Green monkey, Green seaturtle, Hedgehog, Killer whale, Lesser Egyptian jerboa, Manatee, Medium ground finch, Mexican tetra (cavefish), Naked mole-rat, Nile tilapia, Pacific walrus, Painted turtle, Parrot, Peregrine falcon, Pika, Prairie vole, Princess of Burundi, Pundamilia nyererei, Rhesus, Rock pigeon, Saker falcon, Scarlet Macaw, Sheep, Shrew, Spiny softshell turtle, Spotted gar, Squirrel monkey, Star-nosed mole, Tawny puffer fish, Tenrec, Tibetan antelope, Tibetan ground jay, Wallaby, Weddell seal, White rhinoceros, White-throated sparrow, Zebra Mbuna, Zebra finch
Pairwise alignments with the $organism genome were generated for each species using blastz from repeat-masked genomic sequence. Lineage-specific repeats were removed prior to alignment, then reinserted. 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.
An additional filtering step was introduced in the generation of the 60-way conservation track to reduce the number of paralogs and pseudogenes from the high-quality assemblies and the suspect alignments from the low-quality assemblies: the pairwise alignments of high-quality mammalian sequences (placental and marsupial) were filtered based on synteny; those for 2X mammalian genomes were filtered to retain only alignments of best quality in both the target and query ("reciprocal best").
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.
Both phastCons and phyloP are phylogenetic methods that 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 all-species tree model for this track was generated using the phyloFit program from the PHAST package (REV model, EM algorithm, medium precision) using multiple alignments of 4-fold degenerate sites extracted from the 60-way alignment (msa_view). The 4d sites were derived from the RefSeq (Reviewed+Coding) gene set, filtered to select single-coverage long transcripts.
This same tree model was used in the phyloP calculations; however, the background frequencies were modified to maintain reversibility. The resulting tree model: all species,
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. Unlike many conservation-scoring programs, phastCons does not rely on a sliding window of fixed size; therefore, 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.
The phastCons parameters used were: expected-length=45, target-coverage=0.3, rho=0.3.
The phyloP program supports several different methods for computing p-values of conservation or acceleration, for individual nucleotides or larger elements ( http://compgen.cshl.edu/phast/). Here it was used to produce separate scores at each base (--wig-scores option), considering all branches of the phylogeny rather than a particular subtree or lineage (i.e., the --subtree option was not used). The scores were computed by performing a likelihood ratio test at each alignment column (--method LRT), and scores for both conservation and acceleration were produced (--mode CONACC).
The conserved elements were predicted by running phastCons with the --viterbi option. The predicted elements are segments of the alignment that are likely to have been "generated" by the conserved state of the phylo-HMM. Each element is assigned a log-odds score equal to its log probability under the conserved model minus its log probability under the non-conserved model. The "score" field associated with this track contains transformed log-odds scores, taking values between 0 and 1000. (The scores are transformed using a monotonic function of the form a * log(x) + b.) The raw log odds scores are retained in the "name" field and can be seen on the details page or in the browser when the track's display mode is set to "pack" or "full".
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. Thanks to Giacomo Bernardi for help with the fish relationships.
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
Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 2010 Jan;20(1):110-21. PMID: 19858363; PMC: PMC2798823
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
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
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.
Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac 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
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. PMID: 11743200