Significance We introduce a test of the null hypothesis that nucleotide substitution or amino acid replacement processes are independent of gap locations within sequence alignments. When applying this test to… Click to show full abstract
Significance We introduce a test of the null hypothesis that nucleotide substitution or amino acid replacement processes are independent of gap locations within sequence alignments. When applying this test to alignments that are informed by protein structure, the null is rejected about 2/3 of the time. This indicates that modifications are needed to the usual approach of ignoring gap locations when making evolutionary inferences. Additionally, we demonstrate that optimal alignments introduce spurious correlations between gap locations and nucleotide substitution patterns. Because these spurious correlations will not be eliminated by employing genomic-scale datasets, we emphasize the need for modifying the conventional approach of basing evolutionary inferences upon single optimal alignments.
               
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