Models of natural mutations including site heterogeneity

Koshi, Jeffrey M.; Goldstein, Richard A.

doi:10.1002/(sici)1097-0134(19980815)32:3<289::aid-prot4>3.3.co;2-3

Cited by 26 publications

(35 citation statements)

References 24 publications

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“…Amino acid distributions with a similar functional form have also been used previously by other authors (Koshi and Goldstein, 1998;Koshi et al 1999;Dokholyan et al 2001;. Our predictions are in very good agreement with the distributions observed in the Protein Data Bank.…”

Section: Introductionsupporting

confidence: 87%

“…The Gamma distribution is flexible enough to interpolate between broad and narrow distributions, and its free parameter improves considerably the fit between models of evolution and multiple sequence alignments. Subsequently, site-specific amino acid frequencies (Halpern and Bruno, 1998) and site-specific substitution matrices determined for different structural classes (Liò and Goldman, 1998;Koshi and Goldstein, 1998;Koshi et al, 1999;Thorne, 2000;Parisi and Echave, 2001;Fornasari et al, 2002) were shown to further improve the reconstruction of phylogenetic trees. In these works, site-specificity is either empirically derived from the data or simulated with the help of some protein model.…”

Section: Introductionmentioning

confidence: 99%

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Looking at structure, stability, and evolution of proteins through the principal eigenvector of contact matrices and hydrophobicity profiles

Bastolla

Porto

Roman

et al. 2005

Gene

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We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and protein structures as vectors: Structures are represented by the principal eigenvector (PE) of the protein contact matrix, a quantity that resembles closely the effective connectivity of each site; Sequences are represented through the "interactivity" of each amino acid type, using novel parameters that are correlated with hydropathy scales. These interactivity parameters are more strongly correlated than the other hydropathy scales that we examine with: (1) The change upon mutations of the unfolding free energy of proteins with two-states thermodynamics; (2) Genomic properties as the genome-size and the genome-wide GC content; (3) The main eigenvectors of the substitution matrices. The evolutionary average of the interactivity vector correlates very strongly with the PE of a protein structure. Using this result, we derive an analytic expression for site-specific distributions of amino acids across protein families in the form of Boltzmann distributions whose "inverse temperature" is a function of the PE component. We show that our predictions are in agreement with site-specific amino acid distributions obtained from the Protein Data Bank, and we determine the mutational model that best fits the observed site-specific amino acid distributions. Interestingly, the optimal model almost minimizes the rate at which deleterious mutations are eliminated by natural selection.

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Section: Introductionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Looking at structure, stability, and evolution of proteins through the principal eigenvector of contact matrices and hydrophobicity profiles

Bastolla

Porto

Roman

et al. 2005

Gene

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“…Koshi & Goldstein 1998;Huelsenbeck & Nielsen 1999;Lartillot & Philippe 2004;Pagel & Meade 2004;Blackburne et al 2008). For example, we (Pagel & Meade 2004, 2005) reported a mixture model for characterizing what we called 'pattern heterogeneity' in the evolution of nucleotide sequences.…”

Section: Introductionmentioning

confidence: 99%

Modelling heterotachy in phylogenetic inference by reversible-jump Markov chain Monte Carlo

Pagel

Meade

2008

Phil. Trans. R. Soc. B

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The rate at which a given site in a gene sequence alignment evolves over time may vary. This phenomenon-known as heterotachy-can bias or distort phylogenetic trees inferred from models of sequence evolution that assume rates of evolution are constant. Here, we describe a phylogenetic mixture model designed to accommodate heterotachy. The method sums the likelihood of the data at each site over more than one set of branch lengths on the same tree topology. A branch-length set that is best for one site may differ from the branch-length set that is best for some other site, thereby allowing different sites to have different rates of change throughout the tree. Because rate variation may not be present in all branches, we use a reversible-jump Markov chain Monte Carlo algorithm to identify those branches in which reliable amounts of heterotachy occur. We implement the method in combination with our 'pattern-heterogeneity' mixture model, applying it to simulated data and five published datasets. We find that complex evolutionary signals of heterotachy are routinely present over and above variation in the rate or pattern of evolution across sites, that the reversible-jump method requires far fewer parameters than conventional mixture models to describe it, and serves to identify the regions of the tree in which heterotachy is most pronounced. The reversible-jump procedure also removes the need for a posteriori tests of 'significance' such as the Akaike or Bayesian information criterion tests, or Bayes factors. Heterotachy has important consequences for the correct reconstruction of phylogenies as well as for tests of hypotheses that rely on accurate branch-length information. These include molecular clocks, analyses of tempo and mode of evolution, comparative studies and ancestral state reconstruction. The model is available from the authors' website, and can be used for the analysis of both nucleotide and morphological data.

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“…In fact, the physical locations or the directions of the side chains of the residues can be quite different among the residues within a short region in sequence. Recent studies revealed that there was considerable heterogeneity in substitution rate among amino acid positions (32,69). These facts suggest that an analysis of variation at the single-amino-acid-site level would be very important to understanding the nature of variations and elucidating the evolutionary mechanism (5,16,21,44).…”

mentioning

confidence: 99%

Reevaluation of Amino Acid Variability of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein and Prediction of New Discontinuous Epitopes

Yamaguchi-Kabata

Gojobori

2000

J Virol

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To elucidate the evolutionary mechanisms of the human immunodeficiency virus type 1 gp120 envelope glycoprotein at the single-site level, the degree of amino acid variation and the numbers of synonymous and nonsynonymous substitutions were examined in 186 nucleotide sequences for gp120 (subtype B). Analyses of amino acid variabilities showed that the level of variability was very different from site to site in both conserved (C1 to C5) and variable (V1 to V5) regions previously assigned. To examine the relative importance of positive and negative selection for each amino acid position, the numbers of synonymous and nonsynonymous substitutions that occurred at each codon position were estimated by taking phylogenetic relationships into account. Among the 414 codon positions examined, we identified 33 positions where nonsynonymous substitutions were significantly predominant. These positions where positive selection may be operating, which we call putative positive selection (PS) sites, were found not only in the variable loops but also in the conserved regions (C1 to C4). In particular, we found seven PS sites at the surface positions of the ␣-helix (positions 335 to 347 in the C3 region) in the opposite face for CD4 binding. Furthermore, two PS sites in the C2 region and four PS sites in the C4 region were detected in the same face of the protein. The PS sites found in the C2, C3, and C4 regions were separated in the amino acid sequence but close together in the three-dimensional structure. This observation suggests the existence of discontinuous epitopes in the protein's surface including this ␣-helix, although the antigenicity of this area has not been reported yet.The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) interacts with receptors on the target cell and mediates virus entry by fusing the viral and cell membranes. To maintain viral infectivity, amino acids that interact with receptors are expected to be more conserved than other sites on the protein surface. Amino acid changes that reduce the affinity for the receptor will decrease infectivity or survivability, implying that negative selection is operating against amino acid changes on sites for receptor binding. The primary receptor for HIV is CD4 (9), and the secondary receptors are chemokine receptors. The main second receptor for the macrophage-tropic strains is CCR5 (11, 13) and that for T-celltropic strains is CXCR4 (15). In contrast to the functional constraint of amino acids for receptor binding, some amino acid changes in this protein may produce antigenic variations that enable the virus to escape from recognition by the host immune system. Variants with such mutations at antigenic sites will have a higher fitness than others, implying that positive selection is operating against amino acid changes at the antigenic sites. Therefore, both positive and negative selections against amino acid changes are taking place during the evolution of the surface proteins of parasites (48, 66).The relative importance of positive and ne...

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Models of natural mutations including site heterogeneity

Cited by 26 publications

References 24 publications

Looking at structure, stability, and evolution of proteins through the principal eigenvector of contact matrices and hydrophobicity profiles

Looking at structure, stability, and evolution of proteins through the principal eigenvector of contact matrices and hydrophobicity profiles

Modelling heterotachy in phylogenetic inference by reversible-jump Markov chain Monte Carlo

Reevaluation of Amino Acid Variability of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein and Prediction of New Discontinuous Epitopes

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