Biology subjects

Weibel, C.

Publications and source records attributed to Weibel, C..

4 recordsLinked to original sources

bioRxiv2023

A new codon adaptation metric predicts vertebrate body size and tendency to protein disorder

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an "effective population size" is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback-Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder

evolutionary biology↗

bioRxiv2023

The effectiveness of selection in a species affects the direction of amino acid frequency evolution

Nearly neutral theory predicts that species with higher effective population size (Ne) are better at purging slightly deleterious mutations. We compare evolution in high-Ne vs. low-Ne vertebrates to reveal subtle selective preferences among amino acids. We take three complementary approaches. First, we fit non-stationary substitution models using maximum likelihood, comparing the high-Ne clade of rodents and lagomorphs to its low-Ne sister clade of primates and colugos. Second, we compared evolutionary outcomes across a wider range of vertebrates, via correlations between amino acid frequencies and the codon adaptation index of species, a proxy for Ne. Third, we dissected which amino acids substitutions occurred in human, chimpanzee, mouse, and rat, as scored by parsimony - this also enabled comparison to a historical paper. All three methods agree on amino acid preference under more effective selection. Preferred amino acids are less costly to synthesize and use GC-rich codons, which are hard to maintain under AT-biased mutation. These factors explain 85% of the variance in amino acid preferences. Within highly exchangeable pairs of amino acids, arginine is strongly preferred over lysine, valine over isoleucine, and aspartate over glutamate, consistent with more effective selection preferring a marginally larger free energy of folding. The first two of these preferences, but not the third, match differences between thermophiles and mesophilic relatives. These results reveal the biophysical consequences of mutation-selection-drift balance, and demonstrate the utility of nearly neutral theory for understanding protein evolution. Significance statementAccording to the nearly neutral theory of molecular evolution, selection is less able to distinguish between similar alleles in species with lower population size. We identify which amino acids are subject to such weak preferences - these tend to be less costly to make, to use GC-rich codons easily destroyed by mutation, and to be enriched in thermophiles relative to mesophiles. The latter agrees with theories of marginal protein stability under mutation-selection-drift balance.

evolutionary biology↗

bioRxiv2020

The protein domains of vertebrate species in whichselection is more effective have greater intrinsicstructural disorder

The effectiveness of selection varies among species. It is often estimated by means of an "effective population size" based on neutral polymorphism, but this is confounded in complex ways with demography. The strength of codon bias more directly pertains to how well adaptation at many sites can be maintained in the face of deleterious mutations, but past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics, CAIS yields the expected relationship with adult vertebrate body mass. As an example of the use of CAIS, we ask whether protein domains evolve lower intrinsic structural disorder (ISD) when present in more exquisitely adapted species, as expected given that ISD is higher in eukaryotic proteomes than prokaryotic proteomes. Using phylogenetically corrected linear models, we find, contrary to expectations, that the ISD of a given protein domain evolves to be higher when in well-adapted species. This effect is stronger in young protein domains but is also present in ancient domains.

evolutionary biology↗

bioRxiv2020

Universal and taxon-specific trends in protein sequences as a function of age

Extant protein-coding sequences span a huge range of ages, from those that emerged only recently in particular lineages, to those present in the last universal common ancestor. Because evolution has had less time to act on young sequences, there might be "phylostratigraphy" trends in any properties that evolve slowly with age. Indeed, a long-term reduction in hydrophobicity and in hydrophobic clustering has been found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced and dated eukaryotic species, using sensitive HMM methods to detect homology of protein domains (which may vary in age within the same gene), and applying a variety of quality filters. We find that the reduction in hydrophobic clustering is universal across diverse lineages, showing limited sign of saturation. But the tendency for young domains to have higher protein structural disorder, driven primarily by more hydrophilic amino acids, is found only among young animal domains, and not young plant domains, nor ancient domains predating the existence of the last eukaryotic common ancestor. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that events during the earliest stages of life on earth continue to have an impact on the composition of ancient sequences.

evolutionary biology↗