Challenges Finding an optimal alignment of more than two sequences that includes matches mismatches, and gaps, and that takes into account the degree of variation in all of the sequences at the same time poses a very difficult challenge A second computational challenge is identifying a reasonable method of obtaining a cumulative score for the substitutions in the column ot an msa• Finding an optimal alignment of more than two sequences that includes matches, mismatches, and gaps, and that takes into account the degree of variation in all of the sequences at the same time poses a very difficult challenge. • A second computational challenge is identifying a reasonable method of obtaining a cumulative score for the substitutions in the column of an msa. Challenges