119 Vertebrate CoVs Track Settings
 
Multiz Alignment & Conservation (119 strains: strains with vertebrate hosts and human SARS-Cov2)   (All Comparative Genomics tracks)

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Multiz Alignments ▾       Basewise Conservation (phyloP) ▾       Element Conservation (phastCons) ▾      
 
Multiz Alignments Configuration

Species selection:  + - default

  SARS-CoV-2 sequences  + -

sARS-CoV-2/CA6/human/2020/USA
wIV04
betaCoV/Wuhan/IPBCAMS-WH-04/2019
2019-nCoV_WHU01
betaCoV/Wuhan/WH-03/2019
wIV06
betaCoV/Wuhan/YS8011/2020
betaCoV/Hangzhou/HZ-1/2020_20cov-1L
2019-nCoV/USA-CA8/2020
betaCoV/Wuhan/WH19008/2019
betaCoV/Wuhan/WH19005/2019
betaCoV/Wuhan/IPBCAMS-WH-02/2019
sARS0CoV-2/61-TW/human/2020/NPL
sARS-CoV-2/WH-09/human/2020/CHN
2019-nCoV/USA-WI1/2020
2019-nCoV_HKU-SZ-002a_2020
2019-nCoV/USA-WA1/2020
taiwan/NTU01/2020
betaCoV/Wuhan/WH-04/2019
2019-nCoV/Japan/TY/WK-521/2020
2019-nCoV/Japan/TY/WK-501/2020
2019-nCoV/Japan/TY/WK-012/2020
2019-nCoV_HKU-SZ-005b_2020
2019-nCoV/USA-CA7/2020
sARS-CoV-2/IQTC04/human/2020/CHN
sARS-CoV-2/105/human/2020/CHN
sARS-CoV-2/233/human/2020/CHN
sARS-CoV-2/Hu/DP/Kng/19-027
sARS-CoV-2/Hu/DP/Kng/19-020
sARS-CoV-2/SP02/human/2020/BRA
2019-nCoV/USA-AZ1/2020
sARS-CoV-2/Yunnan-01/human/2020/CHN
betaCoV/Finland/1/2020
2019-nCoV/USA-IL1/2020
betaCoV/Korea/SNU01/2020
sARS-CoV-2/01/human/2020/SWE
2019-nCoV/USA-MA1/2020
sARS-CoV-2/WA2/human/2020/USA
sARS-CoV-2/IL2/human/2020/USA
2019-nCoV/USA-CA3/2020
2019-nCoV/USA-CA2/2020
betaCoV/Australia/VIC01/2020
2019-nCoV/USA-TX1/2020
sARS-CoV-2/IQTC03/human/2020/CHN
sARS-CoV-2/IQTC02/human/2020/CHN
betaCoV/Wuhan/IPBCAMS-WH-01/2019
wIV07
2019-nCoV/USA-CA5/2020
2019-nCoV/USA-CA1/2020
betaCoV/Wuhan/WH-01/2019
wIV05
2019-nCoV/Japan/KY/V-029/2020
betaCoV/Japan/AI/I-004/2020
betaCov/Taiwan/NTU02/2020
betaCoV/Wuhan/IPBCAMS-WH-03/2019
2019-nCoV/USA-CA9/2020
betaCoV/Wuhan/IPBCAMS-WH-05/2020
betaCoV/Wuhan/WH19004/2020
wIV02
sARS-CoV-2/IQTC01/human/2020/CHN
betaCoV/Wuhan/WH-02/2019
betaCoV/Wuhan/WH19002/2019

  Other CoV sequences from vertebrate hosts  + -

bat_CoV_TG13
pangolin-CoV-2020_MP789
bat_CoV_BM48-31/BGR/2008
wencheng_Sm_shrew_CoV_Xingguo-101
bat_CoV_HKU4-1
beluga_Whale_CoV_SW1
wigeon_CoV_HKU20
avian_infectious_bronchitis_virus
betaCoV_HKU24_strain_HKU24-R05005I
turkey_CoV
betaCoV_ErinaceusCoV/VMC/2012-174/GER/2012
bat_Hp-betaCoV/Zhejiang2013
betaCoV_England_1
mERS_Middle_East_respiratory_syndrome_CoV
rabbit_CoV_HKU14
night-heron_CoV_HKU19
bovine_CoV
bat_CoV_PREDICT/PDF-2180
bat_CoV_HKU5-1
human_CoV_OC43_strain_ATCC_VR-759
common-moorhen_CoV_HKU21
bulbul_CoV_HKU11-934
human_CoV_HKU1
bat_CoV_HKU9-1
rat_CoV_Parker
btMr-AlphaCoV/SAX2011
mouse_hepatitis_virus_strain_MHV-A59_C12_mutant
magpie-robin_CoV_HKU18
rousettus_bat_CoV_HKU10
rousettus_bat_CoV_GCCDC1_356
sparrow_CoV_HKU17
porcine_CoV_HKU15_strain_HKU15-155
munia_CoV_HKU13-3514
human_CoV_229E
white-eye_CoV_HKU16
coronavirus_AcCoV-JC34
camel_alphaCoV_camel/Riyadh/Ry141/2015
human_Coronavirus_NL63
mink_CoV_strain_WD1127
ferret_CoV_FRCoV-NL-2010
porcine_epidemic_diarrhea_virus
scotophilus_bat_CoV_512
nL63-related_bat_CoV_strain_BtKYNL63-9a
bat_CoV_HKU8
bat_CoV_CDPHE15/USA/2006
thrush_CoV_HKU12-600
btRf-AlphaCoV/HuB2013
lucheng_Rn_rat_CoV_Lucheng-19
bat_CoV_HKU2
btNv-AlphaCoV/SC2013
swine_enteric_CoV_strain_Italy/213306/2009
transmissible_gastroenteritis_virus
bat_CoV_1A
feline_infectious_peritonitis_virus
btRf-AlphaCoV/YN2012
sARS_CoV

Multiple alignment base-level:
Display bases identical to reference as dots
Display chains between alignments

Codon Changes:
Display synonymous and non-synonymous changes in coding exons.

Codon Translation:
Default species to establish reading frame:
No codon translation
Use default species reading frames for translation
Use reading frames for species if available, otherwise no translation
Use reading frames for species if available, otherwise use default species
List subtracks: only selected/visible    all  
 
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 PhyloP  119 virus strains Basewise Conservation by PhyloP   Data format 
 
hide
 PhastCons  119 virus strains Basewise Conservation by PhastCons   Data format 
 
hide
 Multiz Align  Multiz Alignment of 119 strains: red=nonsyn green=syn blue=noncod yellow=noalign   Data format 
Assembly: SARS-CoV-2 Jan. 2020 (NC_045512.2)

Downloads for data in this track are available:

Description

This track shows multiple alignments of 119 virus sequences, aligned to the SARS-CoV-2 reference sequence SARS-CoV-2/NC_045512.2, genome assembly assembly GCF_009858895.2_ASM985889v3. These 119 sequences are from very different coronavirus strains:

  • All 55 reference genomes annotated as "Coronaviridae" in NCBI Viral Genomes. These cover very different vertebrate hosts, from bat to wigeon.
  • A subset of sequences from the 2019/2020 outbreak, from Genbank (52 sequences) and BIGD (12 sequences).
It also includes measurements of evolutionary conservation using two methods (phastCons and phyloP) from the PHAST package, for all 119 virus sequences. 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 (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.

In the track display, the sequence is labeled using its NCBI Nucleotide accession number.

The mapping between sequence accession identifiers and more descriptive names is provided via a text file on our download server.

Display Conventions and Configuration

Pairwise alignments of each species to the SARS-CoV-2 genome are displayed as a series of colored blocks indicating the functional effect of polymorphisms (in pack mode), or as a wiggle (in full mode) that indicates alignment quality. In dense display mode, percent identity of the whole alignments is shown in grayscale using darker values to indicate higher levels of identity.

In pack mode, regions that align with 100% identity are not shown. When there is not 100% percent identity, blocks of four colors are drawn.

  • Red blocks are drawn when a polymorphism in a coding region results in a change in the amino acid that is generated.
  • Green blocks are drawn when a polymorphism in a coding region results in no change to the amino acid that is generated.
  • Blue blocks are drawn when a polymorphism is outside a coding region.
  • Pale yellow blocks are drawn when there are no aligning bases to that region in the reference genome.

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).

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.

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 SARS-CoV-2 sequence at those alignment positions relative to the longest non-SARS-CoV-2 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.

Methods

Pairwise alignments with the reference sequence were generated for each sequence using lastz version 1.04.00. Parameters used for each lastz alignment:

# hsp_threshold      = 2200
# gapped_threshold   = 4000 = L
# x_drop             = 910
# y_drop             = 3400 = Y
# gap_open_penalty   = 400
# gap_extend_penalty = 30
#        A    C    G    T
#   A   91  -90  -25 -100
#   C  -90  100 -100  -25
#   G  -25 -100  100  -90
#   T -100  -25  -90   91
# seed=1110100110010101111 w/transition
# step=1
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. Parameters used in the chaining (axtChain) step: -minScore=10 -linearGap=loose

High-scoring chains were then placed along the genome, with gaps filled by lower-scoring chains, to produce an alignment net.

count sample
date
accession phylogenetic
distance
descriptive name
0012019-12-30NC_045512.20.000000Wuhan-Hu-1
0022020-01-02MN988668.10.0000032019-nCoV WHU01
0032019-12-30MN996528.10.000003WIV04
0042019-12-30MT019532.10.000003BetaCoV/Wuhan/IPBCAMS-WH-04/2019
0052020-01-01LR757996.10.000004BetaCoV/Wuhan/WH-03/2019
0062019-12-30MN996530.10.000006WIV06
0072020-01-20MT039873.10.000006BetaCoV/Hangzhou/HZ-1/2020 20cov-1L
0082020-01-07NMDC60013002-070.000006BetaCoV/Wuhan/YS8011/2020
0092020-01-01MT019533.10.000008BetaCoV/Wuhan/IPBCAMS-WH-05/2020
0102020-02-10MT106053.10.0000082019-nCoV/USA-CA8/2020
0112020-02-23MT118835.10.0000082019-nCoV/USA-CA9/2020
0122019-12-30NMDC60013002-060.000008BetaCoV/Wuhan/WH19008/2019
0132019-12-30MT019531.10.000010BetaCoV/Wuhan/IPBCAMS-WH-03/2019
0142019-12-30NMDC60013002-100.000010BetaCoV/Wuhan/WH19005/2019
0152019-12-30MT019530.10.000011BetaCoV/Wuhan/IPBCAMS-WH-02/2019
0162020-01-13MT072688.10.000012SARS0CoV-2/61-TW/human/2020/NPL
0172020-01-08MT093631.10.000013SARS-CoV-2/WH-09/human/2020/CHN
0182020-01-31MT039887.10.0000142019-nCoV/USA-WI1/2020
0192020-01-29MT027064.10.0000152019-nCoV/USA-CA5/2020
0202020-01-22MN994468.10.0000162019-nCoV/USA-CA2/2020
0212020-01-01NMDC60013002-090.000017BetaCoV/Wuhan/WH19004/2020
0222020-02-05MT066176.10.000018BetaCov/Taiwan/NTU02/2020
0232020-02-10LC528232.10.000020SARS-CoV-2/Hu/DP/Kng/19-020
0242020-02-10LC528233.10.000020SARS-CoV-2/Hu/DP/Kng/19-027
0252019-12-30MN996531.10.000020WIV07
0262019-12-30MN996529.10.000021WIV05
0272020-01-27MT044258.10.000022SARS-CoV-2/CA6/human/2020/USA
0282019-12-26LR757998.10.000023BetaCoV/Wuhan/WH-01/2019
0292019-12-30MN996527.10.000024WIV02
0302020-01-29MT027062.10.0000252019-nCoV/USA-CA3/2020
0312020-02-05MT123290.10.000026SARS-CoV-2/IQTC01/human/2020/CHN
0322020-01-25LC5219250.000027BetaCoV/Japan/AI/I-004/2020
0332020-01-29LC5229720.0000272019-nCoV/Japan/KY/V-029/2020
0342019-12-23MT019529.10.000027BetaCoV/Wuhan/IPBCAMS-WH-01/2019
0352020-02-28MT126808.10.000028SARS-CoV-2/SP02/human/2020/BRA
0362020-01-25MT007544.10.000030BetaCoV/Australia/VIC01/2020
0372020-01-17MT049951.10.000030SARS-CoV-2/Yunnan-01/human/2020/CHN
0382020-02-28MT123292.10.000031SARS-CoV-2/IQTC04/human/2020/CHN
0392020-01-29MT020781.10.000032BetaCoV/Finland/1/2020
0402020-02-06MT106052.10.0000322019-nCoV/USA-CA7/2020
0412020-01-26MT135041.10.000032SARS-CoV-2/105/human/2020/CHN
0422020-01-28MT135043.10.000032SARS-CoV-2/233/human/2020/CHN
0432020-01MN975262.10.0000332019-nCoV_HKU-SZ-005b_2020
0442020-03-05MT152824.10.000033SARS-CoV-2/WA2/human/2020/USA
0452020-02-11MT039888.10.0000342019-nCoV/USA-MA1/2020
0462020-01-31LC5229750.0000352019-nCoV/Japan/TY/WK-521/2020
0472020-01-29LC5229730.0000362019-nCoV/Japan/TY/WK-012/2020
0482020-01-31LC5229740.0000362019-nCoV/Japan/TY/WK-501/2020
0492020-01MN938384.10.0000362019-nCoV_HKU-SZ-002a_2020
0502020-01-19MN985325.10.0000362019-nCoV/USA-WA1/2020
0512020-01-22MN997409.10.0000362019-nCoV/USA-AZ1/2020
0522020-02-11MT106054.10.0000362019-nCoV/USA-TX1/2020
0532020-01-29MT123291.10.000036SARS-CoV-2/IQTC02/human/2020/CHN
0542020-02-28MT123293.10.000036SARS-CoV-2/IQTC03/human/2020/CHN
0552020-01-05LR757995.10.000037BetaCoV/Wuhan/WH-04/2019
0562020-02-01MT066175.10.000037Taiwan/NTU01/2020
0572020-01-23MN994467.10.0000382019-nCoV/USA-CA1/2020
0582020-01-28MT044257.10.000038SARS-CoV-2/IL2/human/2020/USA
0592020-02-07MT093571.10.000038SARS-CoV-2/01/human/2020/SWE
0602020-01-21MN988713.10.0000392019-nCoV/USA-IL1/2020
0612020-01MT039890.10.000040BetaCoV/Korea/SNU01/2020
0622019-12-31LR757997.10.001411BetaCoV/Wuhan/WH-02/2019
0632019-12-30NMDC60013002-050.002318BetaCoV/Wuhan/WH19002/2019
0642013-07-24GWHABKP000000000.126322Bat CoV TG13
0652019-03-01GWHABKW000000000.318494Pangolin-CoV-2020 MP789
0662018-08-13NC_004718.30.885159SARS CoV
0672018-08-13NC_014470.11.088135Bat CoV BM48-31/BGR/2008
0682018-08-13NC_035191.11.483474Wencheng Sm shrew CoV Xingguo-101
0692018-08-13NC_009019.12.026165Bat CoV HKU4-1
0702018-08-13NC_010646.12.170350Beluga Whale CoV SW1
0712018-08-13NC_016995.12.225972Wigeon CoV HKU20
0722018-08-13NC_001451.12.263777Avian infectious bronchitis virus
0732018-08-13NC_026011.12.265050BetaCoV HKU24 strain HKU24-R05005I
0742018-08-13NC_010800.12.317576Turkey CoV
0752018-08-24NC_039207.12.337043BetaCoV ErinaceusCoV/VMC/2012-174/GER/2012
0762018-08-13NC_025217.12.384179Bat Hp-betaCoV/Zhejiang2013
0772018-08-24NC_038294.12.434929BetaCoV England 1
0782018-08-13NC_019843.32.434930MERS Middle East respiratory syndrome CoV
0792018-08-13NC_017083.12.491178Rabbit CoV HKU14
0802018-08-13NC_016994.12.498432Night-heron CoV HKU19
0812018-08-13NC_003045.12.507057Bovine CoV
0822019-03-10NC_034440.12.542837Bat CoV PREDICT/PDF-2180
0832018-08-13NC_009020.12.551785Bat CoV HKU5-1
0842019-02-21NC_006213.12.589639Human CoV OC43 strain ATCC VR-759
0852018-08-13NC_016996.12.598443Common-moorhen CoV HKU21
0862018-08-24NC_011547.12.612548Bulbul CoV HKU11-934
0872018-08-13NC_006577.22.649716Human CoV HKU1
0882018-08-13NC_009021.12.778940Bat CoV HKU9-1
0892018-08-13NC_012936.12.785289Rat CoV Parker
0902018-08-13NC_028811.12.786411BtMr-AlphaCoV/SAX2011
0912018-08-13NC_001846.12.792354Mouse hepatitis virus strain MHV-A59 C12 mutant
0922018-08-13NC_016993.12.828026Magpie-robin CoV HKU18
0932018-08-13NC_018871.12.831499Rousettus bat CoV HKU10
0942018-08-13NC_030886.12.885630Rousettus bat CoV GCCDC1 356
0952018-08-13NC_016992.12.887272Sparrow CoV HKU17
0962018-08-24NC_039208.12.902341Porcine CoV HKU15 strain HKU15-155
0972018-08-13NC_011550.12.936050Munia CoV HKU13-3514
0982018-08-13NC_002645.12.983896Human CoV 229E
0992018-08-13NC_016991.13.002680White-eye CoV HKU16
1002018-08-13NC_034972.13.004210Coronavirus AcCoV-JC34
1012018-08-13NC_028752.13.008138Camel alphaCoV camel/Riyadh/Ry141/2015
1022018-08-13NC_005831.23.009141Human Coronavirus NL63
1032018-08-13NC_023760.13.023450Mink CoV strain WD1127
1042018-08-13NC_030292.13.041640Ferret CoV FRCoV-NL-2010
1052018-08-13NC_003436.13.068747Porcine epidemic diarrhea virus
1062018-08-13NC_009657.13.074701Scotophilus bat CoV 512
1072018-08-13NC_032107.13.086646NL63-related bat CoV strain BtKYNL63-9a
1082018-08-13NC_010438.13.120462Bat CoV HKU8
1092018-08-13NC_022103.13.126101Bat CoV CDPHE15/USA/2006
1102018-08-13NC_011549.13.154652Thrush CoV HKU12-600
1112018-08-13NC_028814.13.185708BtRf-AlphaCoV/HuB2013
1122018-08-13NC_032730.13.203052Lucheng Rn rat CoV Lucheng-19
1132018-08-13NC_009988.13.204418Bat CoV HKU2
1142018-08-13NC_028833.13.260958BtNv-AlphaCoV/SC2013
1152018-08-13NC_028806.13.346396Swine enteric CoV strain Italy/213306/2009
1162018-08-24NC_038861.13.359831Transmissible gastroenteritis virus
1172018-08-13NC_010437.13.404316Bat CoV 1A
1182018-08-13NC_002306.33.472931Feline infectious peritonitis virus
1192018-08-13NC_028824.13.505645BtRf-AlphaCoV/YN2012

The multiple alignment was constructed from the resulting pairwise alignments progressively aligned using multiz/autoMZ. The phylogenetic tree was calculated on 31mer frequency similarity and neighbor joining that distance matrix with the phylip toolset command: neighbor. The reference sequence NC_045512v2 is at the top of the tree:

((((((((((((((((((((((((((((((((((((((((((((((((((((((NC_045512v2 (MN996528v1
MT019532v1)) MN988668v1) LR757996v1) (MN996530v1 NMDC60013002_07)) MT039873v1)
(MT106053v1 NMDC60013002_06)) MT019533v1) MT118835v1) MT019531v1)
NMDC60013002_10) MT019530v1) MT072688v1) MT093631v1) MT039887v1) MT027064v1)
MN994468v1) NMDC60013002_09) MT066176v1) (LC528232v1 LC528233v1)) MN996531v1)
MN996529v1) MT044258v1) LR757998v1) MN996527v1) MT027062v1)
(LC522972 MT123290v1)) MT019529v1) LC521925) MT126808v1)
(((((((LC522973 LC522974) LC522975) (((LR757995v1 MT066175v1) MN985325v1)
(MN938384v1 MN997409v1))) MN975262v1) MT106052v1) (MT135041v1 MT135043v1))
MT049951v1)) MT007544v1) MT123292v1) MT020781v1) MT152824v1) MT039888v1)
(MT123291v1 MT123293v1)) MT106054v1) (MN994467v1 MT044257v1)) MT093571v1)
MN988713v1) MT039890v1) NMDC60013002_05) LR757997v1) GWHABKP00000000)
GWHABKW00000000) NC_004718v3) NC_014470v1) NC_035191v1) (NC_009019v1
((NC_009020v1 ((NC_019843v3 NC_038294v1) NC_034440v1)) NC_039207v1)))
((NC_001451v1 NC_010800v1) ((((NC_011547v1 (NC_011549v1 NC_016991v1))
((NC_011550v1 NC_016993v1) (NC_016992v1 NC_039208v1))) NC_016996v1)
NC_016994v1))) NC_025217v1) (((((NC_001846v1 NC_012936v1) ((NC_003045v1
NC_006213v1) NC_017083v1)) NC_026011v1) NC_006577v2) NC_010646v1))
((((((NC_002306v3 (NC_028806v1 NC_038861v1)) NC_003436v1) (NC_023760v1
NC_030292v1)) (((NC_002645v1 NC_028752v1) (NC_005831v2 NC_032107v1))
(((((NC_009657v1 NC_010437v1) NC_010438v1) ((NC_009988v1 NC_028824v1)
NC_028833v1)) NC_022103v1) (NC_018871v1 NC_028814v1)))) (NC_028811v1
(NC_032730v1 NC_034972v1))) (NC_009021v1 NC_030886v1))) NC_016995v1)
Framing tables from the genes 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 119-way alignment (msa_view). The 4d sites were derived from the NCBI 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.

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 --most-conserved 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, Robert Harris, and Webb Miller of the Penn State Bioinformatics Group
  • 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).
  • Chaining and Netting: axtChain, chainNet by Jim Kent 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

References

Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 2014 Sep 12;345(6202):1369-72. PMID: 25214632; Supplemental Materials and Methods

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