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Correlations between alignment gaps and nucleotide substitution or amino acid replacement

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Correlations between alignment gaps and nucleotide substitution or amino acid replacement
Other Titles
DNA 염기치환 혹은 아미노산 치환과 얼라인먼트 갭의 상관관계
Seo, Tae-Kun
Benjamin D. Redelings
Jeffrey L. Thorne
Issue Date
Seo, Tae-Kun, Benjamin D. Redelings, Jeffrey L. Thorne. 2022. "Correlations between alignment gaps and nucleotide substitution or amino acid replacement". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(34): 1-9.
To assess the conventional treatment in evolutionary inference of alignment gaps as missing data, we propose a simple nonparametric test of the null hypothesis that the locations of alignment gaps are independent of the nucleotide substitution or amino acid replacement process. When we apply the test to 1390 protein alignments that are informed by protein tertiary structure and use a 5% significance level, the null hypothesis of independence between amino acid replacement and gap location is rejected for approximately 65% of data sets. Via simulations that include substitution and insertion-deletion, we show that the test performs well with true alignments. When we simulate according to the null hypothesis and then apply the test to optimal alignments that are inferred by each of four widely-used software packages, the null hypothesis is rejected too frequently. Via further simulations and analyses, we show that the overly frequent rejections of the null hypothesis are not solely due to weaknesses of widely-used software for finding optimal alignments. Instead, our evidence suggests that optimal alignments are unrepresentative of true alignments and that biased evolutionary inferences may result from relying upon individual optimal alignments.
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