Predicting evolutionary change at the DNA level in a natural Mimulus population

Evolution by natural selection occurs when the frequencies of genetic variants change because individuals differ in Darwinian fitness components such as survival or reproductive success. Differential fitness has been demonstrated in field studies of many organisms, but it remains unclear how well we can quantitatively predict allele frequency changes from fitness measurements. Here, we characterize natural selection on millions of Single Nucleotide Polymorphisms (SNPs) across the genome of the annual plant Mimulus guttatus. We use fitness estimates to calibrate population genetic models that effectively predict allele frequency changes into the next generation. Hundreds of SNPs experienced “male selection” in 2013 with one allele at each SNP elevated in frequency among successful male gametes relative to the entire population of adults. In the following generation, allele frequencies at these SNPs consistently shifted in the predicted direction. A second year of study revealed that SNPs had effects on both viability and reproductive success with pervasive trade-offs between fitness components. SNPs favored by male selection were, on average, detrimental to survival. These trade-offs (antagonistic pleiotropy and temporal fluctuations in fitness) may be essential to the long-term maintenance of alleles. Despite the challenges of measuring selection in the wild, the strong correlation between predicted and observed allele frequency changes suggests that population genetic models have a much greater role to play in forward-time prediction of evolutionary change

Macdonald polynomials in superspace: conjectural definition and positivity conjectures

We introduce a conjectural construction for an extension to superspace of the Macdonald polynomials. The construction, which depends on certain orthogonality and triangularity relations, is tested for high degrees. We conjecture a simple form for the norm of the Macdonald polynomials in superspace, and a rather non-trivial expression for their evaluation. We study the limiting cases q=0 and q=\infty, which lead to two families of Hall-Littlewood polynomials in superspace. We also find that the Macdonald polynomials in superspace evaluated at q=t=0 or q=t=\infty seem to generalize naturally the Schur functions. In particular, their expansion coefficients in the corresponding Hall-Littlewood bases appear to be polynomials in t with nonnegative integer coefficients. More strikingly, we formulate a generalization of the Macdonald positivity conjecture to superspace: the expansion coefficients of the Macdonald superpolynomials expanded into a modified version of the Schur superpolynomial basis (the q=t=0 family) are polynomials in q and t with nonnegative integer coefficients.Comment: 18 page

Explicit formulas for the generalized Hermite polynomials in superspace

We provide explicit formulas for the orthogonal eigenfunctions of the supersymmetric extension of the rational Calogero-Moser-Sutherland model with harmonic confinement, i.e., the generalized Hermite (or Hi-Jack) polynomials in superspace. The construction relies on the triangular action of the Hamiltonian on the supermonomial basis. This translates into determinantal expressions for the Hamiltonian's eigenfunctions.Comment: 19 pages. This is a recasting of the second part of the first version of hep-th/0305038 which has been splitted in two articles. In this revised version, the introduction has been rewritten and a new appendix has been added. To appear in JP

Contribution of Endogenous Glucocorticoids and Their Intravascular Metabolism by 11β-HSDs to Postangioplasty Neointimal Proliferation in Mice

Exogenous glucocorticoids inhibit neointimal proliferation in animals. We aime to test the hypothesis that endogenous glucocorticoids influence neointimal proliferation; this may be mediated by effects on systemic risk factors or locally in vessels, and modulated either by adrenal secretion or by enzymes expressed in vessels which mediate local inactivation (11β-HSD2 in endothelium) or regeneration (11β-HSD1 in smooth muscle) of glucocorticoids. Femoral artery wire-angioplasty was conducted in C57Bl/6J, Apo-E(−/−), 11β-HSD1(−/−), Apo-E, 11β-HSD1(−/−) (double knockout) and 11β-HSD2(−/−) mice following glucocorticoid administration, adrenalectomy, glucocorticoid or mineralocorticoid receptor antagonism, or selective 11β-HSD1 inhibition. In C57Bl/6J mice, neointimal proliferation was reduced by systemic or local glucocorticoid administration, unaffected by adrenalectomy, reduced by the mineralocorticoid receptor antagonist eplerenone, and increased by the glucocorticoid receptor antagonist RU38486. 11β-HSD2 deletion had no effect on neointimal proliferation, with or without eplerenone. 11β-HSD1 inhibition or deletion had no effect in chow-fed C57Bl/6J mice, but reduced neointimal proliferation in Apo-E(−/−) mice on Western diet. Reductions in neointimal size were accompanied by reduced macrophage and increased collagen content. We conclude that pharmacological administration of glucocorticoid receptor agonists or of mineralocorticoid receptor antagonists may be useful in reducing neointimal proliferation. Endogenous corticosteroids induce beneficial glucocorticoid receptor activation and adverse mineralocorticoid receptor activation. However, manipulation of glucocorticoid metabolism has beneficial effects only in mice with exaggerated systemic risk factors, suggesting effects mediated primarily in liver and adipose rather than intra-vascular glucocorticoid signalling. Reducing glucocorticoid action with 11β-HSD1 inhibitors that are being developed for type 2 diabetes appears not to risk enhanced neointimal proliferation

Evaluating the multiple-sulfur isotope signature of Eoarchean rocks from the Isua Supracrustal Belt (Southwest-Greenland) by MC-ICP-MS : volcanic nutrient sources for early life

Funding: Australian Research Council - FT210100906; Natural Environment Research Council - NE/V010824/1.On the anoxic Archean Earth, prior to the onset of oxidative weathering, electron acceptors were relatively scarce, perhaps limiting microbial productivity. An important metabolite may have been sulfate produced during the photolysis of volcanogenic SO2 gas. Multiple sulfur isotope data can be used to track this sulfur source, and indeed this record indicates SO2 photolysis dating back to at least 3.7 Ga, that is, as far back as proposed evidence of life on Earth. However, measurements of multiple sulfur isotopes in some key strata from that time can be challenging due to low sulfur concentrations. Some studies have overcome this challenge with NanoSIMS or optimized gas-source mass spectrometry techniques, but those instruments are not readily accessible. Here, we applied an aqua regia leaching protocol to extract small amounts of sulfur from whole rocks for analyses of multiple sulfur isotopes by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Measurements of standards and replicates demonstrate good precision and accuracy. We applied this technique to meta-sedimentary rocks with putative biosignatures from the Eoarchean Isua Supracrustal Belt (ISB, >3.7 Ga) and found positive ∆33S (1.40–1.80‰) in four meta-turbidites and negative ∆33S (−0.80‰ and −0.66‰) in two meta-carbonates. Two meta-basalts do not display significant mass-independent fractionation (MIF, −0.01‰ and 0.16‰). In situ Re–Os dating on a molybdenite vein hosted in the meta-turbidites identifies an early ca. 3.7 Ga hydrothermal phase, and in situ Rb–Sr dating of micas in the meta-carbonates suggests metamorphism affected the rocks at ca. 2.2 and 1.7 Ga. We discuss alteration mechanisms and conclude that there is most likely a primary MIF-bearing phase in these meta-sediments. Our new method is therefore a useful addition to the geochemical toolbox, and it confirms that organisms at that time, if present, may indeed have been fed by volcanic nutrients.Peer reviewe

Jack superpolynomials with negative fractional parameter: clustering properties and super-Virasoro ideals

The Jack polynomials P_\lambda^{(\alpha)} at \alpha=-(k+1)/(r-1) indexed by certain (k,r,N)-admissible partitions are known to span an ideal I^{(k,r)}_N of the space of symmetric functions in N variables. The ideal I^{(k,r)}_N is invariant under the action of certain differential operators which include half the Virasoro algebra. Moreover, the Jack polynomials in I^{(k,r)}_N admit clusters of size at most k: they vanish when k+1 of their variables are identified, and they do not vanish when only k of them are identified. We generalize most of these properties to superspace using orthogonal eigenfunctions of the supersymmetric extension of the trigonometric Calogero-Moser-Sutherland model known as Jack superpolynomials. In particular, we show that the Jack superpolynomials P_{\Lambda}^{(\alpha)} at \alpha=-(k+1)/(r-1) indexed by certain (k,r,N)-admissible superpartitions span an ideal {\mathcal I}^{(k,r)}_N of the space of symmetric polynomials in N commuting variables and N anticommuting variables. We prove that the ideal {\mathcal I}^{(k,r)}_N is stable with respect to the action of the negative-half of the super-Virasoro algebra. In addition, we show that the Jack superpolynomials in {\mathcal I}^{(k,r)}_N vanish when k+1 of their commuting variables are equal, and conjecture that they do not vanish when only k of them are identified. This allows us to conclude that the standard Jack polynomials with prescribed symmetry should satisfy similar clustering properties. Finally, we conjecture that the elements of {\mathcal I}^{(k,2)}_N provide a basis for the subspace of symmetric superpolynomials in N variables that vanish when k+1 commuting variables are set equal to each other.Comment: 36 pages; the main changes in v2 are : 1) in the introduction, we present exceptions to an often made statement concerning the clustering property of the ordinary Jack polynomials for (k,r,N)-admissible partitions (see Footnote 2); 2) Conjecture 14 is substantiated with the extensive computational evidence presented in the new appendix C; 3) the various tests supporting Conjecture 16 are reporte