2022
DOI: 10.1101/2022.12.02.518889
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Evolutionary shortcuts via multi-nucleotide substitutions and their impact on natural selection analyses

Abstract: Inference and interpretation of evolutionary processes - in particular of the types and targets of natural selection affecting coding sequences, are critically influenced by the assumptions built into statistical models for such analyses. If certain aspects of the substitution process (even when they are not of direct interest) are presumed absent or are modeled with too crude of a simplification, estimates of key model parameters can become biased - often systematically, and lead to poor statistical performan… Show more

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Cited by 4 publications
(7 citation statements)
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“…These data are consistent with previous observations synonymous substitution rate variation is common Wisotsky et al, 2020) and that shorter branches tend to be more impacted by multiple hits than longer branches (Lucaci et al, 2023b(Lucaci et al, , 2021 such as the elephant lineage. The best-fitting ABSREL model identified 393 genes with a class of sites with ω>1 at P≤0.05 in the elephant lineage (Figure 1C), whereas the best-fitting BUSTED model identified 427 genes with a class of sites with ω>1 at P≤0.05 in the elephant lineage (Figure 1C); 324 genes were identified as positively selected by both methods (Figure 1D).…”
Section: Hundreds Of Genes Experienced An Episode Of Positive Selecti...supporting
confidence: 93%
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“…These data are consistent with previous observations synonymous substitution rate variation is common Wisotsky et al, 2020) and that shorter branches tend to be more impacted by multiple hits than longer branches (Lucaci et al, 2023b(Lucaci et al, , 2021 such as the elephant lineage. The best-fitting ABSREL model identified 393 genes with a class of sites with ω>1 at P≤0.05 in the elephant lineage (Figure 1C), whereas the best-fitting BUSTED model identified 427 genes with a class of sites with ω>1 at P≤0.05 in the elephant lineage (Figure 1C); 324 genes were identified as positively selected by both methods (Figure 1D).…”
Section: Hundreds Of Genes Experienced An Episode Of Positive Selecti...supporting
confidence: 93%
“…The ABSREL and BUSTED models are variants of the branch-sites random effect likelihood (BSREL) model of coding sequence evolution (Pond et al, 2011a;Smith et al, 2015), which allows for variation in d N /d S (ω) rates across lineages and sites; however, while ABSREL selects the optimal number of rate categories for each gene, BUSTED imposes three rate categories such that ω 1 ≤ω 2 ≤ω 3 (Figure 1B). Both models also accommodate synonymous rate variation across sites [S] , double and triple multi-nucleotide mutations per codon [MH] (Lucaci et al, 2021), and both synonymous rate variation and multi-nucleotide mutations [SMH]; failure to account for synonymous rate variation (Dunn et al, 2019;Rahman et al, 2021;Wisotsky et al, 2020) and multi-nucleotide mutations can lead to widespread false positive inferences of positive selection (Dunn et al, 2019;Lucaci et al, 2023a;Nozawa et al, 2009;Suzuki, 2008;Venkat et al, 2018;Yang and Reis, 2011). We used small sample corrected Akaike Information Criterion values Including synonymous rate variation across sites improved model fit for all genes; however, only 31 genes had significant evidence for multi-nucleotide mutations (Figure 1C).…”
Section: Hundreds Of Genes Experienced An Episode Of Positive Selecti...mentioning
confidence: 99%
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“…This indicates that this change possibly had an adaptive character in the ancestral background. It is important to note, however, that models used for the analysis do not account for variation of synonymous substitution rate and multinucleotide substitution events, which in some cases might lead to false positive results (Lucaci et al , 2023). Because of that, the alternative hypothesis that substitutions Q66H and G109D occurred in the common ancestor of Erwiniaceae due to genetic drift, enabling the subsequent loss of ibpB gene, cannot be fully discounted.…”
Section: Discussionmentioning
confidence: 99%