Progressive sequence alignment as a prerequisitetto correct phylogenetic trees

Abstract

A progressive alignment method is described that utilizes the Needleman and Wunsch pairwise alignment algorithm iteratively to achieve the multiple alignment of a set of protein sequences and to construct an evolutionary tree depicting their relationship. The sequences are assumed a priori to share a common ancestor, and the trees are constructed from difference matrices derived directly from the multiple alignment. The thrust of the method involves putting more trust in the comparison of recently diverged sequences than in those evolved in the distant past. In particular, this rule is followed: "once a gap, always a gap." The method has been applied to three sets of protein sequences: 7 superoxide dismutases, 11 globins, and 9 tyrosine kinase-like sequences. Multiple alignments and phylogenetic trees for these sets of sequences were determined and compared with trees derived by conventional pairwise treatments. In several instances, the progressive method led to trees that appeared to be more in line with biological expectations than were trees obtained by more commonly used methods.

The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4)

“…In those studies we reported that the activated portion of the INT3 protein in MMTV induced mouse mammary tumors shares signi®cant homology with the intracellular domain of members of the NOTCH gene family. In this study we have determined the nucleotide sequence of the complete uninterrupted INT3 RNA transcript and have shown that the organization of the remainder of the encoded protein also shares signi®cant homology with other members of the (Feng and Doolittle, 1987;Higgins and Sharp, 1989) of EGFL-repeats 11 and 12 from di erent members of the NOTCH gene family. MOTCH corresponds to the mouse homologues of NOTCH1, -3, and -4/ INT3; ROTCH2 corresponds to the rat homologue of NOTCH2.…”

Phylogeny for the faint of heart: a tutorial

“…[9]) because the exhaustive alignment of more than six or eight sequences was, and more or less still is, computationally unfeasible. Now, most multiple sequence alignments are constructed by the method known as 'progressive sequence alignment' [10,11]. This method builds an alignment up stepwise, starting with the most similar sequences and progressively adding the more dissimilar ('divergent') ones (Fig.…”

“…The cardinal rule of progressive sequence alignment is 'once a gap always a gap'; gaps can only be added or enlarged, never moved or removed [10]. This is based on the assumption that the best information on gap placement will be found among the most similar sequences, but also for practical purposes; if gaps were adjusted at every step the alignment process would be tremendously slower.…”

C2PA, a new protein expressed during mouse spermatogenesis

“…Protein sequence analysis was performed using the PileUp program provided by the Genetic Computer Group (GCG) package [5].…”