This track shows multiple alignments of 124 insects and measurements of evolutionary conservation using two methods (phastCons and phyloP) from the PHAST package, for all 124 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.
The phylogenetic tree was derived from kmers in common counting between the sequences to obtain a 'distance' matrix, then using the phylip command 'neighbors' operation for the simple neighbor joining algorithm to establish this binary tree. This tree is not necessarily biologically correct, but it does serve as a useful guide tree for the multiz alignment procedure. See also: Phylip distance operations
PhastCons (which has been used in previous Conservation tracks) 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.
See also: lastz parameters and other details, and chain minimum score and gap parameters used in these alignments.
Missing sequence in the assemblies is highlighted in the track display by regions of yellow when zoomed out and Ns displayed at base level (see Gap Annotation, below).
Organism Species Assembly name browser or
NCBI sourcealignment type D. melanogaster Drosophila melanogaster Aug. 2014 (BDGP Release 6 + ISO1 MT/dm6) Aug. 2014 (BDGP Release 6 + ISO1 MT/dm6) reference A. albimanus Anopheles albimanus Aug. 2017 (Anop_albi_ALBI9_A_V2) GCA_000349125.2 net A. aquasalis Anopheles aquasalis Dec. 2017 (A_aquasalis_v1.0) GCA_002846955.1 net A. arabiensis Anopheles arabiensis Apr. 2013 (Anop_arab_DONG5_A_V1) GCA_000349185.1 net A. atroparvus Anopheles atroparvus Sep. 2013 (Anop_atro_EBRO_V1) GCA_000473505.1 net A. christyi Anopheles christyi Apr. 2013 (Anop_chri_ACHKN1017_V1) GCA_000349165.1 net A. coluzzii Anopheles coluzzii Apr. 2008 (m5) GCA_000150765.1 net A. cracens Anopheles cracens Apr. 2017 (ASM209184v1) GCA_002091845.1 net A. culicifacies Anopheles culicifacies Sep. 2013 (Anop_culi_species_A-37_1_V1) GCA_000473375.1 net A. darlingi Anopheles darlingi Dec. 2013 (A_darlingi_v1) GCA_000211455.3 net A. dirus Anopheles dirus Mar. 2013 (Anop_diru_WRAIR2_V1) GCA_000349145.1 net A. epiroticus Anopheles epiroticus Mar. 2013 (Anop_epir_epiroticus2_V1) GCA_000349105.1 net A. farauti Anopheles farauti Jan. 2014 (Anop_fara_FAR1_V2) GCA_000473445.2 net A. farauti_No4 Anopheles farauti No. 4 Mar. 2015 (ASM95621v1) GCA_000956215.1 net A. funestus Anopheles funestus Mar. 2013 (Anop_fune_FUMOZ_V1) GCA_000349085.1 net A. gambiae Anopheles gambiae Oct. 2006 (AgamP3/anoGam3) Oct. 2006 (AgamP3/anoGam3) net A. gambiae_1 Anopheles gambiae str. PEST Oct. 2006 (AgamP3) GCF_000005575.2 net A. koliensis Anopheles koliensis Mar. 2015 (ASM95627v1) GCA_000956275.1 net A. maculatus Anopheles maculatus Apr. 2017 (ASM209183v1) GCA_002091835.1 net A. melas Anopheles melas Jan. 2014 (Anop_mela_CM1001059_A_V2) GCA_000473525.2 net A. mellifera Apis mellifera 04 Nov 2010 (Amel_4.5/apiMel4) 04 Nov 2010 (Amel_4.5/apiMel4) net A. merus Anopheles merus Jan. 2014 (Anop_meru_MAF_V1) GCA_000473845.2 net A. minimus Anopheles minimus Mar. 2013 (Anop_mini_MINIMUS1_V1) GCA_000349025.1 net A. nili Anopheles nili Jul. 2013 (Anili1) GCA_000439205.1 net A. punctulatus Anopheles punctulatus Mar. 2015 (ASM95625v1) GCA_000956255.1 net A. quadriannulatus Anopheles quadriannulatus Mar. 2013 (Anop_quad_QUAD4_A_V1) GCA_000349065.1 net A. sinensis Anopheles sinensis Jul. 2014 (AS2) GCA_000441895.2 net A. stephensi Anopheles stephensi Sep. 2018 (ASM344897v1) GCA_003448975.1 net Aedes_aegypti Aedes aegypti Jun. 2017 (AaegL5.0) GCF_002204515.2 net Aedes_albopictus Aedes albopictus Jan. 2017 (canu_80X_arrow2.2) GCF_001876365.2 net Bactrocera_dorsalis Bactrocera dorsalis Dec. 2014 (ASM78921v2) GCF_000789215.1 net Bactrocera_latifrons Bactrocera latifrons Oct. 2016 (ASM185335v1) GCF_001853355.1 net Bactrocera_oleae Bactrocera oleae Jul. 2015 (gapfilled_joined_lt9474.gt500.covgt10) GCF_001188975.1 net Bactrocera_tryoni Bactrocera tryoni May 2014 (Assembly_2.2_of_Bactrocera_tryoni_genome) GCA_000695345.1 net Belgica_antarctica Belgica antarctica Sep. 2014 (ASM77530v1) GCA_000775305.1 net Calliphora_vicina Calliphora vicina Jun. 2015 (ASM101727v1) GCA_001017275.1 net Ceratitis_capitata Ceratitis capitata Nov. 2017 (Ccap_2.1) GCF_000347755.3 net Chaoborus_trivitattus Chaoborus trivitattus May 2015 (ASM101481v1) GCA_001014815.1 net Chironomus_riparius Chironomus riparius May 2015 (ASM101450v1) GCA_001014505.1 net Chironomus_tentans Chironomus tentans Nov. 2014 (CT01) GCA_000786525.1 net Cirrula_hians Cirrula hians May 2015 (ASM101507v1) GCA_001015075.1 net Clogmia_albipunctata Clogmia albipunctata May 2015 (ASM101494v1) GCA_001014945.1 net Clunio_marinus Clunio marinus Nov. 2016 (CLUMA_1.0) GCA_900005825.1 net Coboldia_fuscipes Coboldia fuscipes May 2015 (ASM101433v1) GCA_001014335.1 net Condylostylus_patibulatus Condylostylus patibulatus May 2015 (ASM101487v1) GCA_001014875.1 net Culex_quinquefasciatus Culex quinquefasciatus Apr. 2007 (CulPip1.0) GCF_000209185.1 net Culicoides_sonorensis Culicoides sonorensis Feb. 2018 (Cson_Genome_version_2.0) GCA_900258525.2 net D. albomicans Drosophila albomicans 21 May 2012 (DroAlb_1.0/droAlb1) 21 May 2012 (DroAlb_1.0/droAlb1) net D. americana Drosophila americana Oct. 2015 (D._americana_H5_strain_genome_assembly) GCA_001245395.1 net D. ananassae Drosophila ananassae Feb. 2006 (Agencourt CAF1/droAna3) Feb. 2006 (Agencourt CAF1/droAna3) syntenic D. arizonae Drosophila arizonae May 2016 (ASM165402v1) GCF_001654025.1 syntenic D. athabasca Drosophila athabasca Jun. 2018 (ASM318502v1) GCA_003185025.1 syntenic D. biarmipes Drosophila biarmipes 04 Mar 2013 (Dbia_2.0/droBia2) 04 Mar 2013 (Dbia_2.0/droBia2) syntenic D. bipectinata Drosophila bipectinata 04 Mar 2013 (Dbip_2.0/droBip2) 04 Mar 2013 (Dbip_2.0/droBip2) net D. busckii Drosophila busckii Sep. 2015 (ASM127793v1) GCF_001277935.1 syntenic D. elegans Drosophila elegans 04 Mar 2013 (Dele_2.0/droEle2) 04 Mar 2013 (Dele_2.0/droEle2) net D. erecta Drosophila erecta Feb. 2006 (Agencourt CAF1/droEre2) Feb. 2006 (Agencourt CAF1/droEre2) syntenic D. eugracilis Drosophila eugracilis 04 Mar 2013 (Deug_2.0/droEug2) 04 Mar 2013 (Deug_2.0/droEug2) net D. ficusphila Drosophila ficusphila 04 Mar 2013 (Dfic_2.0/droFic2) 04 Mar 2013 (Dfic_2.0/droFic2) net D. grimshawi Drosophila grimshawi Feb. 2006 (Agencourt CAF1/droGri2) Feb. 2006 (Agencourt CAF1/droGri2) syntenic D. hydei Drosophila hydei Nov. 2017 (ASM278046v1) GCF_002780465.1 net D. kikkawai Drosophila kikkawai 04 Mar 2013 (Dkik_2.0/droKik2) 04 Mar 2013 (Dkik_2.0/droKik2) net D. miranda Drosophila miranda 19 Apr 2013 (DroMir_2.2/droMir2) 19 Apr 2013 (DroMir_2.2/droMir2) syntenic D. mojavensis Drosophila mojavensis Feb. 2006 (Agencourt CAF1/droMoj3) Feb. 2006 (Agencourt CAF1/droMoj3) syntenic D. montana Drosophila montana May 2018 (ASM308661v1) GCA_003086615.1 net D. nasuta Drosophila nasuta Jul. 2017 (ASM222288v1) GCA_002222885.1 net D. navojoa Drosophila navojoa May 2016 (ASM165401v1) GCF_001654015.1 syntenic D. novamexicana Drosophila novamexicana Jul. 2018 (DnovRS1) GCA_003285875.1 syntenic D. obscura Drosophila obscura Jul. 2017 (Dobs_1.0) GCF_002217835.1 net D. persimilis Drosophila persimilis Oct. 2005 (Broad/droPer1) Oct. 2005 (Broad/droPer1) net D. pseudoobscura Drosophila pseudoobscura pseudoobscura 11 Apr 2013 (Dpse_3.0/droPse3) 11 Apr 2013 (Dpse_3.0/droPse3) syntenic D. pseudoobscura_1 Drosophila pseudoobscura pseudoobscura Apr. 2013 (Dpse_3.0) GCF_000001765.3 net D. rhopaloa Drosophila rhopaloa 22 Feb 2013 (Drho_2.0/droRho2) 22 Feb 2013 (Drho_2.0/droRho2) net D. sechellia Drosophila sechellia Oct. 2005 (Broad/droSec1) Oct. 2005 (Broad/droSec1) syntenic D. serrata Drosophila serrata Apr. 2017 (Dser1.0) GCF_002093755.1 net D. simulans Drosophila simulans Sep. 2014 (ASM75419v2/droSim2) Sep. 2014 (ASM75419v2/droSim2) syntenic D. subobscura Drosophila subobscura Nov. 2017 (Dsub_1.0) GCA_002749795.1 net D. suzukii Drosophila suzukii 30 Sep 2013 (Dsuzukii.v01/droSuz1) 30 Sep 2013 (Dsuzukii.v01/droSuz1) net D. takahashii Drosophila takahashii 04 Mar 2013 (Dtak_2.0/droTak2) 04 Mar 2013 (Dtak_2.0/droTak2) net D. virilis Drosophila virilis Feb. 2006 (Agencourt CAF1/droVir3) Feb. 2006 (Agencourt CAF1/droVir3) syntenic D. willistoni Drosophila willistoni 03 Aug 2006 (dwil_caf1/droWil2) 03 Aug 2006 (dwil_caf1/droWil2) syntenic D. yakuba Drosophila yakuba 27 Jun 2006 (dyak_caf1/droYak3) 27 Jun 2006 (dyak_caf1/droYak3) syntenic Ephydra_gracilis Ephydra gracilis May 2015 (ASM101467v1) GCA_001014675.1 net Eristalis_dimidiata Eristalis dimidiata May 2015 (ASM101514v1) GCA_001015145.1 net Eutreta_diana Eutreta diana May 2015 (ASM101511v1) GCA_001015115.1 net Glossina_austeni Glossina austeni May 2014 (Glossina_austeni-1.0.3) GCA_000688735.1 net Glossina_brevipalpis Glossina brevipalpis May 2014 (Glossina_brevipalpis_1.0.3) GCA_000671755.1 net Glossina_fuscipes Glossina fuscipes fuscipes May 2014 (Glossina_fuscipes-3.0.2) GCA_000671735.1 net Glossina_morsitans_1 Glossina morsitans May 2015 (ASM101451v1) GCA_001014515.1 net Glossina_morsitans_2 Glossina morsitans morsitans Mar. 2014 (ASM107743v1) GCA_001077435.1 net Glossina_pallidipes Glossina pallidipes May 2014 (Glossina_pallidipes-1.0.3) GCA_000688715.1 net Glossina_palpalis_gambiensis Glossina palpalis gambiensis Jan. 2015 (Glossina_palpalis_gambiensis-2.0.1) GCA_000818775.1 net Haematobia_irritans Haematobia irritans May 2018 (Hi_v1.0) GCA_003123925.1 net Hermetia_illucens Hermetia illucens May 2015 (ASM101489v1) GCA_001014895.1 net Holcocephala_fusca Holcocephala fusca May 2015 (ASM101521v1) GCA_001015215.1 net Liriomyza_trifolii Liriomyza trifolii May 2015 (ASM101493v1) GCA_001014935.1 net Lucilia_cuprina Lucilia cuprina Dec. 2017 (Lcup_2.0) GCF_000699065.1 net Lucilia_sericata Lucilia sericata May 2015 (ASM101483v1) GCA_001014835.1 net Lutzomyia_longipalpis Lutzomyia longipalpis Jun. 2012 (Llon_1.0) GCA_000265325.1 net M. domestica Musca domestica 22 Apr 2013 (Musca_domestica-2.0.2/musDom2) 22 Apr 2013 (Musca_domestica-2.0.2/musDom2) net Mayetiola_destructor Mayetiola destructor Oct. 2010 (Mdes_1.0) GCA_000149185.1 net Megaselia_abdita Megaselia abdita May 2015 (ASM101517v1) GCA_001015175.1 net Megaselia_scalaris Megaselia scalaris Mar. 2013 (ASM34191v2) GCA_000341915.2 net Mochlonyx_cinctipes Mochlonyx cinctipes May 2015 (ASM101484v1) GCA_001014845.1 net Neobellieria_bullata Neobellieria bullata Jun. 2015 (ASM101745v1) GCA_001017455.1 net Paykullia_maculata Paykullia maculata Apr. 2018 (ASM305512v1) GCA_003055125.1 net Phlebotomus_papatasi Phlebotomus papatasi May 2012 (Ppap_1.0) GCA_000262795.1 net Phormia_regina Phormia regina Sep. 2016 (ASM173554v1) GCA_001735545.1 net Phortica_variegata Phortica variegata May 2015 (ASM101441v1) GCA_001014415.1 net Proctacanthus_coquilletti Proctacanthus coquilletti Jan. 2017 (200kmer_750.trimmed) GCA_001932985.1 net Rhagoletis_zephyria Rhagoletis zephyria Jul. 2016 (Rhagoletis_zephyria_1.0) GCF_001687245.1 net Sarcophagidae_BV_2014 Sarcophagidae sp. BV-2014 Jul. 2015 (ASM104719v1) GCA_001047195.1 net Scaptodrosophila_lebanonensis Scaptodrosophila lebanonensis Jul. 2018 (SlebRS1) GCA_003285725.1 net Sphyracephala_brevicornis Sphyracephala brevicornis May 2015 (ASM101523v1) GCA_001015235.1 net Stomoxys_calcitrans Stomoxys calcitrans May 2015 (Stomoxys_calcitrans-1.0.1) GCF_001015335.1 net T. castaneum Tribolium castaneum Sep. 2005 (Baylor 2.0/triCas2) Sep. 2005 (Baylor 2.0/triCas2) net Teleopsis_dalmanni Teleopsis dalmanni Jul. 2017 (Tel_dalmanni_2A_v1.0) GCA_002237135.1 net Tephritis_californica Tephritis californica Jun. 2015 (ASM101751v1) GCA_001017515.1 net Themira_minor Themira minor May 2015 (ASM101457v1) GCA_001014575.1 net Tipula_oleracea Tipula oleracea Jun. 2015 (ASM101753v1) GCA_001017535.1 net Trichoceridae_BV_2014 Trichoceridae sp. BV-2014 May 2015 (ASM101442v1) GCA_001014425.1 net Trupanea_jonesi Trupanea jonesi May 2015 (ASM101466v1) GCA_001014665.1 net Zaprionus_indianus Zaprionus indianus Oct. 2016 (ZP_IN_1.0) GCA_001752445.1 net Zeugodacus_cucurbitae Zeugodacus cucurbitae Dec. 2014 (ASM80634v1) GCF_000806345.1 net
Downloads for data in this track are available:
- Multiz alignments (MAF format), and phylogenetic trees
- PhyloP conservation (WIG format)
- PhastCons conservation (WIG format)
Display Conventions and Configuration
The track configuration options allow the user to display the three different clade sets of scores, all, Brachycera, Nematocera or Holometabola, individually or all simultaneously. In full and pack display modes, conservation scores are displayed as a wiggle track (histogram) in which the height reflects the value 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. Configuration buttons are available to select all of the species (Set all), deselect all of the species (Clear all), or use the default settings (Set defaults). 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.
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 $organism 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 $organism 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 $organism sequence at those alignment positions relative to the longest non-$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:
- 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 (Table 2).
Table 2. Gene tracks used for codon translation.
Gene Track Species NCBI RefSeq Genes D. persimilis Ensembl Genes v68 D. erecta, D. ananassae, D. melanogaster Xeno RefGene D. sechellia no annotations all others Methods
Pairwise alignments with the $organism genome were generated for each species using lastz from repeat-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. Please note the specific parameters for the alignments. 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 for each species, see the description pages for the Chain and Net tracks.
An additional filtering step was introduced in the generation of the 124-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: some of the pairwise alignments were filtered based on synteny; and some were filtered to retain only alignments of best quality in both the target and query ("reciprocal best"). See also: D. melanogaster/dm6 124-way alignment filtering parameters. The column alignment type indicates the type of filtering.
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.
Phylogenetic Tree Model
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 124-way alignment (msa_view). The 4d sites were derived from the NCBI RefSeq gene set, filtered to select single-coverage long transcripts.
This same tree model was used in the phyloP calculations, however their background frequencies were modified to maintain reversibility. The resulting tree model for all species.
PhastCons Conservation
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.
PhyloP Conservation
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).
Conserved Elements
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".
Credits
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, phyloP, phyloFit, tree_doctor, msa_view and other programs in PHAST by Adam Siepel at Cold Spring Harbor Laboratory (original development done at the Haussler lab at UCSC).
- 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 Murphy et al. (2001) and general consensus in the vertebrate phylogeny community as of March 2007.
References
Phylip distance operations:
Fan H, Ives A, Surget_groba Y, Cannon C. An assembly and alignment-free method of phylogeny reconstruction from next-generation sequencing data. BMC Genomics. 2015; 16(1): 522. PMID: 26169061
Bernard G, Ragan M, Chana C.X. Recapitulating phylogenies using k-mers: from trees to networks. F1000Res. 2016; 5: 2789. PMID: 28105314
Phylo-HMMs, phastCons, and phyloP:
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
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
Lastz (formerly Blastz):
Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468
Harris RS. 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
Phylogenetic Tree:
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