ORCID Profile
0000-0003-0518-6783
Current Organisation
Uppsala University
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Publisher: eLife Sciences Publications, Ltd
Date: 06-07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 26-03-2020
DOI: 10.1101/2020.03.26.010728
Abstract: 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 erse 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.
Publisher: eLife Sciences Publications, Ltd
Date: 26-07-2023
Abstract: 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 ersity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic ersity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. 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) that corrects for both confounders. Unlike previous metrics of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.
Publisher: Cold Spring Harbor Laboratory
Date: 03-03-2023
DOI: 10.1101/2023.03.02.530449
Abstract: 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 ersity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic ersity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. 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) that corrects for both confounders. Unlike previous metrics of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.
Publisher: Cold Spring Harbor Laboratory
Date: 28-10-2022
DOI: 10.1101/2022.10.27.514087
Abstract: Protein domains that emerged more recently in evolution have higher structural disorder and greater clustering of hydrophobic residues along the primary sequence. It is hard to explain how selection acting via descent with modification could act so slowly as not to saturate over the extraordinarily long timescales over which these trends persist. Here we hypothesize that the trends were created by a higher level of selection that differentially affects the retention probabilities of protein domains with different properties. This hypothesis predicts that loss rates should depend on disorder and clustering trait values. To test this, we inferred loss rates via maximum likelihood for animal Pfam domains, after first performing a set of stringent quality control methods to reduce annotation errors. Intermediate trait values, matching those of ancient domains, are associated with the lowest loss rates, making our results difficult to explain with reference to previously described homology detection biases. Simulations confirm that effect sizes are of the right magnitude to produce the observed long-term trends. Our results support the hypothesis that differential domain loss slowly weeds out those protein domains that have non-optimal levels of disorder and clustering. The same preferences also shape differential ersification of Pfam domains, further impacting proteome composition.
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2023
DOI: 10.1101/2023.02.01.526552
Abstract: Nearly neutral theory predicts that the effectiveness of natural selection will vary with species’ neutral genetic ersity, or effective population size ( N e ). This relationship allows comparisons among species with different effective population sizes to reveal subtle selective preferences for a variety of traits. We investigate one such trait – amino acid composition – and find that the efficacy of selection, measured as the Codon Adaptation Index of Species (CAIS), can predict amino acid frequencies across vertebrates. In addition to amino acid frequency (an evolutionary outcome), we also measure amino acid flux (an evolutionary process) on the branches separating mouse and rat, and compare it to flux on the branches separating human and chimpanzee. We decompose flux into a shared component that reflects a variety of universal artifacts, and a species-specific component capturing any effects of N e . The shared component of flux is correlated with structural disorder propensity. The species component is correlated with selective preference as measured by CAIS, i.e., the two methods agree on which amino acids are preferred under more effective selection, with the CAIS method providing higher statistical resolution, and producing a correlation with random peptide fitness effects. Within highly exchangeable pairs of amino acids, arginine is strongly preferred over lysine, and valine over isoleucine. Interestingly, these preferences match how thermophiles tend to differ from mesophilic relatives, as expected from theories of marginal protein stability at mutation-selection-drift balance.
Publisher: Cold Spring Harbor Laboratory
Date: 16-10-2020
DOI: 10.1101/2020.10.15.341313
Abstract: 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 ex le 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.
Publisher: eLife Sciences Publications, Ltd
Date: 08-01-2021
DOI: 10.7554/ELIFE.57347
Abstract: Extant protein-coding sequences span a huge range of ages, from those that emerged only recently 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. A long-term reduction in hydrophobicity and hydrophobic clustering was found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced species, using sensitive HMM methods to detect protein domain homology. We find that the reduction in hydrophobic clustering is universal across lineages. However, only young animal domains have a tendency to have higher structural disorder. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that the composition of the contemporary descendants of ancient sequences reflects amino acid availability during the earliest stages of life, when these sequences first emerged.
Publisher: Oxford University Press (OUP)
Date: 06-2016
DOI: 10.1093/GBE/EVW120
Publisher: Oxford University Press (OUP)
Date: 22-03-2023
Abstract: Protein domains that emerged more recently in evolution have a higher structural disorder and greater clustering of hydrophobic residues along the primary sequence. It is hard to explain how selection acting via descent with modification could act so slowly as not to saturate over the extraordinarily long timescales over which these trends persist. Here, we hypothesize that the trends were created by a higher level of selection that differentially affects the retention probabilities of protein domains with different properties. This hypothesis predicts that loss rates should depend on disorder and clustering trait values. To test this, we inferred loss rates via maximum likelihood for animal Pfam domains, after first performing a set of stringent quality control methods to reduce annotation errors. Intermediate trait values, matching those of ancient domains, are associated with the lowest loss rates, making our results difficult to explain with reference to previously described homology detection biases. Simulations confirm that effect sizes are of the right magnitude to produce the observed long-term trends. Our results support the hypothesis that differential domain loss slowly weeds out those protein domains that have nonoptimal levels of disorder and clustering. The same preferences also shape the differential ersification of Pfam domains, thereby further impacting proteome composition.
Publisher: eLife Sciences Publications, Ltd
Date: 26-07-2023
DOI: 10.7554/ELIFE.87335
Abstract: 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 ersity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic ersity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. 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) that corrects for both confounders. Unlike previous metrics of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jennifer James.