Human-mouse-rat alignments

Glenn Tesler
March 16, 2004
Links updated November 2024

Assembly versions
Downloadable data
Alignment coordinates from PatternHunter
Anchor coordinates from GRIMM-Anchors
Synteny block coordinates from GRIMM-Synteny
Discussion of X chromosome reconstruction (separate document)

This is the data for

G. Bourque, P.A. Pevzner and G. Tesler, Reconstructing the Genomic Architecture of Ancestral Mammals: Lessons From Human, Mouse, and Rat Genomes, Genome Research, 14 no. 4 (2004), 507-516.
Journal link: doi:10.1101/gr.1975204

Please cite the above if you use this data. If you use the PatternHunter anchors, please also cite

B. Ma, J. Tromp, M. Li, PatternHunter: Faster And More Sensitive Homology Search. Bioinformatics. 18(3):440-445, 2002.
Journal link: doi:10.1093/bioinformatics/18.3.440

Assembly versions

These are the IDs of the assemblies that we analyzed in 2003; UCSC has removed these older assemblies from their website and they are no longer available to download.

Organism	Assembly name	Chromosomes	Original URL (no longer available)
Human	UCSC hg15 (NCBI build 33)	1-22, X, Y; M ignored	http://genome.ucsc.edu/goldenPath/10april2003/bigZips/
Mouse	UCSC mm3 (NCBI build 30)	1-19, X	http://genome.ucsc.edu/goldenPath/mmFeb2003/bigZips/
Rat	UCSC rn3 (Baylor HGSC v. 3.1)	1-20, X; Un ignored	http://genome.ucsc.edu/goldenPath/rnJun2003/bigZips/

Downloadable data

	PatternHunter alignment coordinates	GRIMM-Anchors uncompressed anchors	GRIMM-Anchors compressed anchors	GRIMM-Synteny 300 kb blocks	GRIMM-Synteny 1 Mb blocks
human-mouse	gzip (40,315,854 bytes)	gzip (11,612,600 bytes)	gzip (1,949,496 bytes)	html text	html text
human-rat	gzip (40,793,358 bytes)	gzip (10,828,461 bytes)	gzip (1,791,448 bytes)	html text	html text
mouse-rat	gzip (272,624,055 bytes)	gzip (24,567,603 bytes)	gzip (708,977 bytes)	html text	html text
human-mouse-rat	not applicable	gzip (6,828,062 bytes)	gzip (1,041,309 bytes)	html text	text

The formats of the above files are described below. In addition, other members of the Rat Genome Sequencing Consortium made related data for the same assemblies available at http://www.genboree.org. The files may no longer be available, however.

PatternHunter alignments

The assemblies were first masked at UCSC with RepeatMasker and TandemRepeatFinder. Bin Ma ran PatternHunter to align the non-masked portions of the sequences. The coordinates of the regions that were masked were available at UCSC in the directories listed above, but are no longer available.

PatternHunter does base-by-base alignments of 2 sequences. It was run with each combination of two species, and also with each species vs. itself. (I did some processing of the latter for the purpose of analyzing repeats, but we will not be using it in the present set of papers.)

I parsed out the coordinates from the PatternHunter output and put them into my own format. Even the coordinate files without the detailed alignments are still very large.

If you have used PatternHunter directly, please note that the format below is my own format, useful to me for GRIMM-Synteny, and is different than PatternHunter's.

Each line has these fields:

	ID chr1 start1 end1 chr2 start2 end2 sign score evalue

for example:

	1 1 28574062 28575652 X 54629503 54631092 - 1367 0.0
	2 1 28574062 28575652 X 54726654 54728243 + 1355 0.0
	3 1 243490236 243492219 X 15479260 15481161 - 1017 0.0

ID: Due to concatenating a large number of separate PatternHunter output files and then filtering them, PatternHunter's ID number isn't unique or useful any more.
genome number: human-mouse: human=1, mouse=2
human-rat: human=1, rat=2
mouse-rat: mouse=1, rat=2
For example, in the file human-mouse.gz, (chr1,start1,end1) refer to human and (chr2,start2,end2) refer to mouse.
chr1, chr2: The chromosomes are denoted by their name as a string.
start1, end1, start2, end2: The start/end are 0-based on the + strand. The intervals are half-closed, half-open: [start,end).
sign: The sign is '+' or '-'. Negative means to take the string of bases from the interval as indicated on the + strands of both genomes/chromosomes, but then reverse complement one of those strings to align it to the other. See more on this below.
score: Higher scores are better alignments.
evalue: Lower evalues are better alignments.

Note on signs

The coordinates are 0-based on the positive strand. If the sign field is negative, it indicates that you take the sequence from the positive strand at the specified coordinates, and then reverse complement it:

   position   0  1  2  3  4  5  6  7  8  9
   + strand  [A] C  T  A  G  C  C  A  T  G
   - strand  [T] G  A  T  C  G  G  T  A  C

so position 0 with a sign + is "A" in the leftmost column, + strand row, and position 0 with a sign - is "T" in the leftmost column - strand row. I've marked that position with brackets.

Note that other conventions are also in use, such as:

   position   0  1  2  3  4  5  6  7  8  9
   + strand  [A] C  T  A  G  C  C  A  T  G
   - strand  [T] G  A  T  C  G  G  T  A  C
   position   9  8  7  6  5  4  3  2  1  0

where that position is identified as 0 on the + strand and 9 on the - strand. There are also variations where one or both strands are 1-based, the strands are indicated by positive/negative coordinates, etc.

GRIMM-Anchors coordinate files

PatternHunter's alignment coordinates were heavily processed to produce 2-way and 3-way anchors. These come in "uncompressed" and (lossy) "compressed" versions. The compression is appropriate for the purposes of GRIMM-Synteny; if it is not appropriate for your purposes, use the uncompressed version. The compression method is this: Sort the anchors in order for every species. Consecutive anchors in the first species are combined together if

in all other species they are consecutive in the exact same order as the first species or the exact reverse order (with all signs inverted as well)
and the anchors are close in all species (sum over species of gap between two consecutive anchors is < 50000 in 2-species comparisons or < 75000 in 3-species comparisons).

In the 2-species version, each line has these fields:

	ID chr1 start1 end1 chr2 start2 end2 sign

In the 3-species version:

	ID chr1 start1 end1 sign1 chr2 start2 end2 sign2 chr3 start3 end3 sign3

ID: Anchors are sorted in order by first genome and numbered consecutively.
genome number: human-mouse: human=1, mouse=2
human-rat: human=1, rat=2
mouse-rat: mouse=1, rat=2
human-mouse-rat: human=1, mouse=2, rat=3
chr1, chr2, chr2: The chromosomes are denoted by their name as a string.
start1, end1, start2, end2, start3, end3: The start/end are 0-based on the + strand. The intervals are half-closed, half-open: [start,end).
sign (2 species): The sign is '+' or '-'. Negative means to take the string of bases from the interval as indicated on the + strands of both genomes/chromosomes, but then reverse complement one of those strings to align it to the other. See more on this above.
sign1, sign2, sign3 (3 species): Each sign is '+' or '-'. Positive means to take the string of bases from the interval as indicated on the + strand of the appropriate genome. Negative means to take from the positive positions for that genome and then reverse complement the string. See more on this above.

GRIMM-Synteny coordinate files

Next, there are several synteny block files. There are 2-way comparisons in which only PatternHunter alignments between those two species were used, and the 3rd species played no role whatsoever. There are also 3-way comparisons.

The file blocks_hmr_1000000 is human-mouse-rat blocks at 1 Mb resolution. The genome #'s in this file can be derived from the filename (order h,m,r: genome 1 = human, genome 2 = mouse, genome 3 = rat). Similarly, in hr_1000000, genome 1 = human and genome 2 = rat. And so on.

Resolution x (300000 or 1000000) means that the length of the every block in the first genome is >= x and the GRIMM-Synteny "gap threshold" is x (in the 2-species files) or 1.5*x (in the 3-species files). We may change the definitions and parameters in future runs.

The first line of the file is "# " plus tab-separated names of the columns. Each subsequent line is a 2 or 3-way synteny block. The files are sorted in order by chromosome and then starting position in genome 1.

cluster_number: The ID assigned to that synteny block.
org1.chrom, org1.start, org1.end, org1.sign: are the chromosome # (as described above), start and end (as closed interval), and sign (1 or -1), for whatever genome 1 is in that file.
org1.pos: an integer sequence 1,2,... giving the order of the synteny blocks on chromosome org1.chrom of genome 1.
org2.*, org3.*: similar