ArticleGenome research2011
High sensitivity to aligner and high rate of false positives in the estimates of positive selection in the 12 Drosophila genomes.
Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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84 citing papers in PubMed.
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- Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond.iScience · 2023Article
- Phylotranscriptomic Analyses of Mycoheterotrophic Monocots Show a Continuum of Convergent Evolutionary Changes in Expressed Nuclear Genes From Three Independent Nonphotosynthetic Lineages.Genome biology and evolution · 2023Article
- Signatures of Positive Selection in the Genome ofLife (Basel, Switzerland) · 2022Article
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- Intermolecular Interactions Drive Protein Adaptive and Coadaptive Evolution at Both Species and Population Levels.Molecular biology and evolution · 2022Article
- Evidence of episodic positive selection inPeerJ · 2022Article
- Frequent lineage-specific substitution rate changes support an episodic model for protein evolution.G3 (Bethesda, Md.) · 2021Article
- The Birth-and-Death Evolution of Cytochrome P450 Genes in Bees.Genome biology and evolution · 2021Article
- Relative model selection of evolutionary substitution models can be sensitive to multiple sequence alignment uncertainty.BMC ecology and evolution · 2021Article
- Variation in the Evolution and Sequences of Proglucagon and the Receptors for Proglucagon-Derived Peptides in Mammals.Frontiers in endocrinology · 2021Article
- From Inquilines to Gall Inducers: Genomic Signature of a Life-Style Transition in Synergus Gall Wasps.Genome biology and evolution · 2020Article
- DGINN, an automated and highly-flexible pipeline for the detection of genetic innovations on protein-coding genes.Nucleic acids research · 2020Article
- Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
24 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
We investigate the effect of aligner choice on inferences of positive selection using site-specific models of molecular evolution. We find that independently of the choice of aligner, the rate of false positives is unacceptably high. Our study is a whole-genome analysis of all protein-coding genes in 12 Drosophila genomes annotated in either all 12 species (~6690 genes) or in the six melanogaster group species. We compare six popular aligners: PRANK, T-Coffee, ClustalW, ProbCons, AMAP, and MUSCLE, and find that the aligner choice strongly influences the estimates of positive selection. Differences persist when we use (1) different stringency cutoffs, (2) different selection inference models, (3) alignments with or without gaps, and/or additional masking, (4) per-site versus per-gene statistics, (5) closely related melanogaster group species versus more distant 12 Drosophila genomes. Furthermore, we find that these differences are consequential for downstream analyses such as determination of over/under-represented GO terms associated with positive selection. Visual analysis indicates that most sites inferred as positively selected are, in fact, misaligned at the codon level, resulting in false positive rates of 48%-82%. PRANK, which has been reported to outperform other aligners in simulations, performed best in our empirical study as well. Unfortunately, PRANK still had a high, and unacceptable for most applications, false positives rate of 50%-55%. We identify misannotations and indels, many of which appear to be located in disordered protein regions, as primary culprits for the high misalignment-related error levels and discuss possible workaround approaches to this apparently pervasive problem in genome-wide evolutionary analyses.
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