Playing with blocks: some pitfalls of forcing multiple alignments.
Block alignments of multiple amino acid sequences are useful representations of regions thought to share common ancestry and function. Often the block alignments are motivated by the expectation that a protein of interest is similar in function to members of a family of proteins. However, when alignments are forced by using ad hoc methods, it is often difficult to decide whether the proposed relationship is valid. Visual examination can be deceptive, especially when alignments are not carried out in the context of controls subjected to similar procedures. Even computer-aided methods can be misleading when biases are introduced. To illustrate some of the problems that can arise, a few examples from the literature are analyzed. It is concluded that when standard methods fail to find an interesting block alignment unaided by human intervention, then the result should be regarded with caution.
Henikoff
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Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D000818:Animals; D015982:Bias; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016208:Databases, Factual; D004926:Escherichia coli; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010363:Pattern Recognition, Automated; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012324:RNA-Dependent RNA Polymerase; D002268:Carboxypeptidases; D043424:Carboxypeptidase B; D000604:Amino Acyl-tRNA Synthetases