Detecting macroevolutionary genotype–phenotype associations using error-corrected rates of protein convergence

Abstract

On macroevolutionary timescales, extensive mutations and phylogenetic uncertainty mask the signals of genotype–phenotype associations underlying convergent evolution. To overcome this problem, we extended the widely used framework of non-synonymous to synonymous substitution rate ratios and developed the novel metric ωC, which measures the error-corrected convergence rate of protein evolution. While ωC distinguishes natural selection from genetic noise and phylogenetic errors in simulation and real examples, its accuracy allows an exploratory genome-wide search of adaptive molecular convergence without phenotypic hypothesis or candidate genes. Using gene expression data, we explored over 20 million branch combinations in vertebrate genes and identified the joint convergence of expression patterns and protein sequences with amino acid substitutions in functionally important sites, providing hypotheses on undiscovered phenotypes. We further extended our method with a heuristic algorithm to detect highly repetitive convergence among computationally non-trivial higher-order phylogenetic combinations. Our approach allows bidirectional searches for genotype–phenotype associations, even in lineages that diverged for hundreds of millions of years.

Increased positive selection in highly recombining genes does not necessarily reflect an evolutionary advantage of recombination

“…This suggests that contrarily to the previous example, fitness at one site does not always depends on the amino-acids present at other sites. In this sense, there is also accumulating evidence for convergent adaptation at the molecular level (Christin et al, 2007; Zhen et al, 2012; Davies et al, 2012; Wu et al, 2020; Duchemin et al, 2023; Fukushima and Pollock, 2023), suggesting that there is sometimes a limited number of mutations that can lead to a given phenotype, and thus limited opportunities for compensatory mutations. Moreover, an important role of beneficial back mutations have been reported in plants (Chen et al, 2021) and mammals (Moses and Durbin, 2009; Latrille et al, 2023).…”

“…In this sense, there is also accumulating evidence for convergent adaptation at the molecular level (Christin et al, 2007;Zhen et al, 2012;Davies et al, 2012;Wu et al, 2020;Duchemin et al, 2023;Fukushima and Pollock, 2023), suggesting that there is sometimes a limited number of mutations that can lead to a given phenotype, and thus limited opportunities for compensatory mutations. Moreover, an important role Increased positive selection in highly recombining genes does not necessarily reflect an evolutionary advantage of recombination of beneficial back mutations have been reported in plants (Chen et al, 2021) and mammals (Moses and Durbin, 2009;Latrille et al, 2023).…”

Age, metabolisms, and potential origin of dominant anammox bacteria in the global oxygen-deficient zones

“…Also based on the alignment, a maximum-likelihood phylogenetic tree was inferred using IQ-TREE v1.5.5 [ 59 ] with the best-fit LG + R6 substitution model. The resulting phylogenetic tree was rooted at desired branches using the tree manipulating tool nwkit [ 72 ], and the total sequence number (101) and the tree number (1) were manually added as the top line of the Newick tree file.…”

Physicochemical Perspective of Biological Heterogeneity

“…On a broader scale, intercellular and organismal heterogeneity are evident in the diverse cell types, tissues, and organs that collectively form an organism. Going further, organisms of the same species vary from molecular to phenotypical level . Understanding and characterizing heterogeneity in biology has become increasingly important in fields like personalized medicine, where individual variations in genetic makeup and cellular behavior can impact disease susceptibility, progression, and treatment responses …”