Benchmarking multi-rate codon models

CITATION: Delport, W. et al. 2010. Benchmarking multi-rate codon models. PLoS ONE, 5(7): e11587, doi:10.1371/journal.pone.0011587.The original publication is available at http://journals.plos.org/plosoneThe single rate codon model of non-synonymous substitution is ubiquitous in phylogenetic modeling. Indeed, the use of a non-synonymous to synonymous substitution rate ratio parameter has facilitated the interpretation of selection pressure on genomes. Although the single rate model has achieved wide acceptance, we argue that the assumption of a single rate of non-synonymous substitution is biologically unreasonable, given observed differences in substitution rates evident from empirical amino acid models. Some have attempted to incorporate amino acid substitution biases into models of codon evolution and have shown improved model performance versus the single rate model. Here, we show that the single rate model of non-synonymous substitution is easily outperformed by a model with multiple non-synonymous rate classes, yet in which amino acid substitution pairs are assigned randomly to these classes. We argue that, since the single rate model is so easy to improve upon, new codon models should not be validated entirely on the basis of improved model fit over this model. Rather, we should strive to both improve on the single rate model and to approximate the general time-reversible model of codon substitution, with as few parameters as possible, so as to reduce model over-fitting. We hint at how this can be achieved with a Genetic Algorithm approach in which rate classes are assigned on the basis of sequence information content. © 2010 Delport et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011587Publisher's versio

Irreducible Representations of Diperiodic Groups

The irreducible representations of all of the 80 diperiodic groups, being the symmetries of the systems translationally periodical in two directions, are calculated. To this end, each of these groups is factorized as the product of a generalized translational group and an axial point group. The results are presented in the form of the tables, containing the matrices of the irreducible representations of the generators of the groups. General properties and some physical applications (degeneracy and topology of the energy bands, selection rules, etc.) are discussed.Comment: 30 pages, 5 figures, 28 tables, 18 refs, LaTex2.0

CodonTest: Modeling Amino Acid Substitution Preferences in Coding Sequences

Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models. However, these approaches have been limited by the necessity for large alignments in their estimation. An alternative approach is to assume that substitution rates between amino acid pairs can be subdivided into rate classes, dependent on the information content of the alignment. However, given the combinatorially large number of such models, an efficient model search strategy is needed. Here we develop a Genetic Algorithm (GA) method for the estimation of such models. A GA is used to assign amino acid substitution pairs to a series of rate classes, where is estimated from the alignment. Other parameters of the phylogenetic Markov model, including substitution rates, character frequencies and branch lengths are estimated using standard maximum likelihood optimization procedures. We apply the GA to empirical alignments and show improved model fit over existing models of codon evolution. Our results suggest that current models are poor approximations of protein evolution and thus gene and organism specific multi-rate models that incorporate amino acid substitution biases are preferred. We further anticipate that the clustering of amino acid substitution rates into classes will be biologically informative, such that genes with similar functions exhibit similar clustering, and hence this clustering will be useful for the evolutionary fingerprinting of genes

INTERPERSONAL RELATIONS AND GROUP PROCESSES Putting the Brakes on Aggression Toward a Romantic Partner: The Inhibitory Influence of Relationship Commitment

Why do people behave aggressively toward romantic partners, and what can put the brakes on this aggression? Provocation robustly predicts aggression in both intimate and nonintimate relationships. Four methodologically diverse studies tested the hypothesis that provocation severity and relationship commitment interact to predict aggression toward one's romantic partner, with the aggression-promoting effects of provocation diminishing as relationship commitment increases. Across all four studies, commitment to one's romantic relationship inhibited aggression toward one's partner when individuals were severely (but not mildly) provoked. Study 4 tested the hypothesis that this Partner Provocation ϫ Commitment interaction effect would be strong among individuals high in dispositional tendencies toward retaliation but weak (perhaps even nonexistent) among individuals low in such tendencies. Discussion emphasizes the importance of understanding instigating, impelling, and inhibiting processes in the perpetration of aggression toward intimate partners. Keywords: romantic relationships, commitment, aggression, I 3 theory Although romantic relationships often begin with chocolates and roses, eventually thorns are sure to emerge. Indeed, precisely because of the deep interdependence that characterizes these relationships, romantic partners have a particularly pronounced capacity to be infuriating. Whether by flirting with others, criticizing our flaws, thoughtlessly neglecting our needs and desires, or by other omissions and commissions, romantic partners can sometimes provoke angry responses. Such provocation frequently triggers an urge toward retaliation, perhaps even toward aggression. When will provoked people aggress toward their romantic partner, and what might put the brakes on their aggression? In the current investigation, we test the hypothesis that partner provocation increases aggressive tendencies toward one's partner, especially among individuals who are weakly (vs. strongly) committed to their partner. The logic underlying this prediction is that partner provocation frequently triggers an urge toward aggressive retaliation but that relationship commitment helps individuals override this urge. Partner Provocation in Intimate Relationships Although people typically expect that romantic relationships will be rewarding, most individuals experience some amount of conflict with their romantic partner. Indeed, conflict is "an inevitable-though often unanticipated-feature of close relationships. The strong, frequent, and diverse bonds between [romantic partners] set the stage for conflicting interests to surface&quot

I=3/2 KπK \pi Scattering in the Nonrelativisitic Quark Potential Model

We study $I=3/2$ elastic $K\pi$ scattering to Born order using nonrelativistic quark wavefunctions in a constituent-exchange model. This channel is ideal for the study of nonresonant meson-meson scattering amplitudes since s-channel resonances do not contribute significantly. Standard quark model parameters yield good agreement with the measured S- and P-wave phase shifts and with PCAC calculations of the scattering length. The P-wave phase shift is especially interesting because it is nonzero solely due to $SU(3)_f$ symmetry breaking effects, and is found to be in good agreement with experiment given conventional values for the strange and nonstrange constituent quark masses.Comment: 12 pages + 2 postscript figures, Revtex, MIT-CTP-210

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial

The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor–positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology)

Evolution and Survival on Eutherian Sex Chromosomes

Since the two eutherian sex chromosomes diverged from an ancestral autosomal pair, the X has remained relatively gene-rich, while the Y has lost most of its genes through the accumulation of deleterious mutations in nonrecombining regions. Presently, it is unclear what is distinctive about genes that remain on the Y chromosome, when the sex chromosomes acquired their unique evolutionary rates, and whether X-Y gene divergence paralleled that of paralogs located on autosomes. To tackle these questions, here we juxtaposed the evolution of X and Y homologous genes (gametologs) in eutherian mammals with their autosomal orthologs in marsupial and monotreme mammals. We discovered that genes on the X and Y acquired distinct evolutionary rates immediately following the suppression of recombination between the two sex chromosomes. The Y-linked genes evolved at higher rates, while the X-linked genes maintained the lower evolutionary rates of the ancestral autosomal genes. These distinct rates have been maintained throughout the evolution of X and Y. Specifically, in humans, most X gametologs and, curiously, also most Y gametologs evolved under stronger purifying selection than similarly aged autosomal paralogs. Finally, after evaluating the current experimental data from the literature, we concluded that unique mRNA/protein expression patterns and functions acquired by Y (versus X) gametologs likely contributed to their retention. Our results also suggest that either the boundary between sex chromosome strata 3 and 4 should be shifted or that stratum 3 should be divided into two strata

Interleukin-15 Treatment Induces Weight Loss Independent of Lymphocytes

Obesity is a chronic inflammatory condition characterized by activation and infiltration of proinflammatory immune cells and a dysregulated production of proinflammatory cytokines. While known as a key regulator of immune natural killer (NK) cell function and development, we have recently demonstrated that reduced expression of the cytokine Interleukin-15 (IL-15) is closely linked with increased body weight and adiposity in mice and humans. Previously, we and others have shown that obese individuals have lower circulating levels of IL-15 and NK cells. Lean IL-15 overexpressing (IL-15 tg) mice had an accumulation in adipose NK cells compared to wildtype and NK cell deficient obese IL-15−/− mice. Since IL-15 induces weight loss in IL-15−/− and diet induced obese mice and has effects on various lymphocytes, the aim of this paper was to determine if lymphocytes, particularly NK cells, play a role in IL-15 mediated weight loss. Acute IL-15 treatment resulted in an increased accumulation of NK, NKT, and CD3+ T cells in adipose tissue of B6 mice. Mice depleted of NK and NKT cells had similar weight loss comparable to controls treated with IL-15. Finally, IL-15 treatment induces significant weight loss in lymphocyte deficient RAG2−/−γc−/− mice independent of food intake. Fat pad cross-sections show decreased pad size with cytokine treatment is due to adipocyte shrinkage. These results clearly suggest that IL-15 mediates weight loss independent of lymphocytes