Phylogenetic assessment of alignments reveals neglected tree signal in gaps

By Christophe Dessimoz, Manuel Gil. 2010

138 citations recorded by the source corpus.

BackgroundThe alignment of biological sequences is of chief importance to most evolutionary and comparative genomics studies, yet the two main approaches used to assess alignment accuracy have flaws: reference alignments are derived from the biased sample of proteins with known structure, and simulated data lack realism.ResultsHere, we introduce tree-based tests of alignment accuracy, which not only use large and representative samples of real biological data, but also enable the evaluation of the effect of gap placement on phylogenetic inference. We show that (i) the current belief that consistency-based alignments outperform scoring matrix-based alignments is misguided; (ii) gaps carry substantial phylogenetic signal, but are poorly exploited by most alignment and tree building programs; (iii) even so, excluding gaps and variable regions is detrimental; (iv) disagreement among alignment programs says little about the accuracy of resulting trees.ConclusionsThis study provides the broad community relying on sequence alignment with important practical recommendations, sets superior standards for assessing alignment accuracy, and paves the way for the development of phylogenetic inference methods of significantly higher resolution.

Subfields: Molecular Biology, Paleontology

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Citations in the corpus

MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability (2013, background): “Because of its high performance (Nuin et al. 2006; Golubchik et al. 2007; Dessimoz and Gil 2010; Letsch et al. 2010; Sahraeian and Yoon 2011; Sievers et al. 2011), MAFFT is becoming popular in recent years.”
Survey of Branch Support Methods Demonstrates Accuracy, Power, and Robustness of Fast Likelihood-based Approximation Schemes (2011, background): “A recently proposed framework for more objective testing on real data is a promising step (Dessimoz and Gil 2010).”
PhyloSuite: An integrated and scalable desktop platform for streamlined molecular sequence data management and evolutionary phylogenetics studies (2019, methodology): “…generated by the above software programs, but it should be used with utmost caution, as sometimes it may cause the loss of the coding frame in a protein‐ coding sequence if the “Codons” option is not used, and otherwise negatively affect the downstream phylogenetic analyses (Dessimoz & Gil, 2010).”
Class of multiple sequence alignment algorithm affects genomic analysis. (2013, background): “Other possible benchmarks have been investigated, for example, the gaps placed by Prank may contain a stronger phylogenetic signal than similarity-MSAMs (Dessimoz and Gil 2010), suggesting that gap placement in evolution-MSAMs may be more accurate.”
webPRANK: a phylogeny-aware multiple sequence aligner with interactive alignment browser (2010, methodology): “The alignments generated using the algorithm have been found to perform well in phylogenetic alignment benchmarks based on both real [4] and simulated [2] data, and give the most accurate inference of selection on codon sequences [5].”
Accurate extension of multiple sequence alignments using a phylogeny-aware graph algorithm (2012, methodology): “The phylogeny-aware algorithm based on these ideas and implemented in the program PRANK performs very well in evolutionary alignment comparisons (Dessimoz and Gil, 2010; Fletcher and Yang, 2010; Jordan and Goldman, 2012; Markova-Raina and Petrov, 2011).”