Description

This track shows multiple alignments of 7 human coronavirus sequences, aligned to the SARS-CoV-2 NCBI reference sequence SARS-CoV-2 for NC_045512.2, genome assembly GCF_009858895.2_ASM985889v3. The multiple alignments were generated using Multiz and other tools in the UCSC/Penn State Bioinformatics comparative genomics alignment pipeline.

In the track display, the sequences are labeled using common names. Note the table below to relate these common names to the NCBI assembly accession identifier.

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 (+), deselect all of the species (-), or use the default settings (Reset to defaults).

For text nucleotide alignments, click on the alignment tracks. To view detailed information about the alignments at a specific position, zoom to a small region or click the 'base' button to see amino acid alignments.

Base Level

When zoomed-in to the base-level display, the track shows the amino acid 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 can be turned off in base-level display mode if desired. You can 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 1.04.03. Parameters used for each LASTZ alignment:

# hsp_threshold      = 3000
# gapped_threshold   = 3000 = L
# x_drop             = 910
# y_drop             = 9400 = Y
# gap_open_penalty   = 400
# gap_extend_penalty = 30
#        A    C    G    T
#   A   91 -114  -31 -123
#   C -114  100 -125  -31
#   G  -31 -125  100 -114
#   T -123  -31 -114   91
# seed=1110100110010101111 w/2 transitions
# step=1

-minScore=1000 -linearGap=loose

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

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:

((((SARS_CoV_2 SARS_CoV_1) MERS) (OC43 HKU1)) (CoV229E NL63))

Data Access

Downloads for data in this track are available:

• Multiz alignments (MAF format), and phylogenetic trees

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