DISTMATP

Creates a distance matrix from multiple alignments

distmat calculates the evolutionary distances between every pair ofsequences in a multiple alignment. The sequences need to be alignedbefore running this program. The quality of the alignment is ofparamount importance in obtaining meaningful information from thisanalysis. This application calculates a distance matrix for the set ofsequences in the alignment. The distances are expressed in terms of thenumber of substitutions per 100 bases or amino acids.

As sequence diverge so does the probability of there being multiplesubstitutions at any one site in the alignment increase. The distancewill then be an underestimate of the true evolutionary distance betweenthe sequences. Therefore, there are a number of methods for correctingthe observed substitution rate for the occurence of multiplesubstutions.

For nucleotides, the "-position" flag allows the user to choose basepositions to analyse in each codon, i.e. 123 (all bases), 12 (the firsttwo bases), 1, 2, or 3 individual bases.

Uncorrected distances

S = m/(npos + gaps*gap_penalty)                                  (1)m 	    - score of matches (1 for an exact match, a fraction for partial	      matches and 0 for no match)npos	    - number of positions included in mgaps        - number of gaps in the sequencesgap_penalty - the score given to a gapped position

D = uncorrected distance = p-distance = 1-S          (2)

The score of match includes all exact matches. For nucleotides, if theflag "-ambiguous" is used then partial matches are included in thescore. For example, a match of M (A or C) with A will increment m by 0.5(0.5*1.0). Gaps are not included in the calculation unless a non zerovalue is given with "-gapweight". It should be noted that end gaps andinternal gaps will be weighted by the same amount. So it is recommendedthat this be used with "-sbegin"and "-send" to specify the start and endof the region to calculate the distance from.

Multiple Substitution correction algorithms

Jukes-Cantor

distance = -b ln (1-D/b)D - uncorrected distanceb - constant. b= 3/4 for nucleotides and 19/20 for proteins.

Partial matches and gap positions can be taken into account in thecalculation of D, by setting the "-ambiguous" and "-gapweight" flags(see "uncorrected distance" method).

Reference:
"Phylogenetic Inference", Swofford, Olsen, Waddell, andHillis, in Molecular Systematics, 2nd ed., Sinauer Ass., Inc., 1996, Ch. 11.

Tajima-Nei

A = 1, T = 2, C = 3, G = 4b = 0.5(1.- Sum(i=A,G)(fraction[i]^2  + D^2/h)h = Sum(i=A,C)Sum(k=T,G) (0.5 * pair_frequency[i,k]^2/(fraction[i]*fraction[k]))distance = -b ln(1.-D/b)pair_frequency[i,k]   - frequency of the i and k base pair at sites in			the alignement of the pair of sequences.fraction[i]           - average content of the base i in both sequences

Reference:
F. Tajima and M. Nei, Mol. Biol. Evol. 1984, 1, 269.

Kimura Two-Parameter distance

P = transitions/nposQ = transversions/nposnpos - number of positions scoreddistance = -0.5 ln[ (1-2P-Q)*sqrt(1-2Q)]

Reference:
M. kimura, J. Mol. Evol. 1980, 16, 111.

Tamura

P = transitions/nposQ = transversions/nposnpos - number of positions scoredGC1 = GC fraction in sequence 1GC2 = GC fraction in sequence 2C = GC1 + GC2 - 2*GC1*GC2distance = -C ln(1-P/C-Q) - 0.5(1-C) ln(1-2Q)

Reference:
K. Tamura, Mol. Biol. Evol. 1992, 9, 678.

Jin-Nei Gamma distance

L = average substituition = transition_rate + 2 * transversion_ratea = (average L)^2/(variance of L)P = transitions/nposQ = transversions/nposnpos - number of positions scoreddistance = 0.5 * a ((1-2P-Q)^(-1/a) + 0.5 (1-2Q)^(-1/a) -3/2)

It is suggested [Jin et al.], in general, that the distance becalculated with an a-value of 1. However, the user can specify their ownvalue, using the "-parametera" option, or calculate for each pair ofsequence, using "-calculatea".

Reference:
L. Jin and M. Nei, Mol. Biol. Evol. 1990, 7, 82.

Kimura Protein distance

S = m/nposm  - exact matchnpos - number of positions scoredD = 1-Sdistance = -ln(1 - D - 0.2D^2)

Reference:
M. Kimura, The Neutral Theory of Molecular Evolution, Camb. Uni. Press,Camb., 1983.

1. "Phylogenetic Inference", Swofford, Olsen, Waddell, and Hillis, in Molecular Systematics, 2nd ed., Sinauer Ass., Inc., 1996, Ch. 11.
2. F. Tajima and M. Nei, Mol. Biol. Evol. 1984, 1, 269.
3. M. Kimura, J. Mol. Evol. 1980, 16, 111.
4. K. Tamura, Mol. Biol. Evol. 1992, 9, 678.
5. L. Jin and M. Nei, Mol. Biol. Evol. 1990, 7, 82.
6. M. Kimura, The Neutral Theory of Molecular Evolution, Camb. Uni. Press, Camb., 1983.