A genomic map of the effects of linked selection in Drosophila

Natural selection at one site shapes patterns of genetic variation at linked sites. Quantifying the effects of 'linked selection' on levels of genetic diversity is key to making reliable inference about demography, building a null model in scans for targets of adaptation, and learning about the dynamics of natural selection. Here, we introduce the first method that jointly infers parameters of distinct modes of linked selection, notably background selection and selective sweeps, from genome-wide diversity data, functional annotations and genetic maps. The central idea is to calculate the probability that a neutral site is polymorphic given local annotations, substitution patterns, and recombination rates. Information is then combined across sites and samples using composite likelihood in order to estimate genome-wide parameters of distinct modes of selection. In addition to parameter estimation, this approach yields a map of the expected neutral diversity levels along the genome. To illustrate the utility of our approach, we apply it to genome-wide resequencing data from 125 lines in Drosophila melanogaster and reliably predict diversity levels at the 1Mb scale. Our results corroborate estimates of a high fraction of beneficial substitutions in proteins and untranslated regions (UTR). They allow us to distinguish between the contribution of sweeps and other modes of selection around amino acid substitutions and to uncover evidence for pervasive sweeps in untranslated regions (UTRs). Our inference further suggests a substantial effect of linked selection from non-classic sweeps. More generally, we demonstrate that linked selection has had a larger effect in reducing diversity levels and increasing their variance in D. melanogaster than previously appreciated

The Generation of Direction Selectivity in the Auditory System

Both human speech and animal vocal signals contain frequency-modulated (FM) sounds. Although central auditory neurons that selectively respond to the direction of frequency modulation are known, the synaptic mechanisms underlying the generation of direction selectivity (DS) remain elusive. Here we show the emergence of DS neurons in the inferior colliculus by mapping the three major subcortical auditory nuclei. Cell-attached recordings reveal a highly reliable and precise firing of DS neurons to FM sweeps in a preferred direction. By using in vivo whole-cell current-clamp and voltage-clamp recordings, we found that the synaptic inputs to DS neurons are not direction selective, but temporally reversed excitatory and inhibitory synaptic inputs are evoked in response to opposing directions of FM sweeps. The construction of such temporal asymmetry, resulting DS, and its topography can be attributed to the spectral disparity of the excitatory and the inhibitory synaptic tonal receptive fields

Direct Observation of the Superfluid Phase Transition in Ultracold Fermi Gases

Water freezes into ice, atomic spins spontaneously align in a magnet, liquid helium becomes superfluid: Phase transitions are dramatic phenomena. However, despite the drastic change in the system's behaviour, observing the transition can sometimes be subtle. The hallmark of Bose-Einstein condensation (BEC) and superfluidity in trapped, weakly interacting Bose gases is the sudden appearance of a dense central core inside a thermal cloud. In strongly interacting gases, such as the recently observed fermionic superfluids, this clear separation between the superfluid and the normal parts of the cloud is no longer given. Condensates of fermion pairs could be detected only using magnetic field sweeps into the weakly interacting regime. The quantitative description of these sweeps presents a major theoretical challenge. Here we demonstrate that the superfluid phase transition can be directly observed by sudden changes in the shape of the clouds, in complete analogy to the case of weakly interacting Bose gases. By preparing unequal mixtures of the two spin components involved in the pairing, we greatly enhance the contrast between the superfluid core and the normal component. Furthermore, the non-interacting wings of excess atoms serve as a direct and reliable thermometer. Even in the normal state, strong interactions significantly deform the density profile of the majority spin component. We show that it is these interactions which drive the normal-to-superfluid transition at the critical population imbalance of 70(5)%.Comment: 16 pages (incl. Supplemental Material), 5 figure

Automated Selection of Active Orbital Spaces

One of the key challenges of quantum-chemical multi-configuration methods is the necessity to manually select orbitals for the active space. This selection requires both expertise and experience and can therefore impose severe limitations on the applicability of this most general class of ab initio methods. A poor choice of the active orbital space may yield even qualitatively wrong results. This is obviously a severe problem, especially for wave function methods that are designed to be systematically improvable. Here, we show how the iterative nature of the density matrix renormalization group combined with its capability to include up to about one hundred orbitals in the active space can be exploited for a systematic assessment and selection of active orbitals. These benefits allow us to implement an automated approach for active orbital space selection, which can turn multi-configuration models into black box approaches.Comment: 29 pages, 10 figures, 5 table

On the spectral density from instantons in quenched QCD

We investigate the contribution of instantons to the eigenvalue spectrum of the Dirac operator in quenched QCD. The instanton configurations that we use have been derived, elsewhere, from cooled SU(3) lattice gauge fields and, for comparison, we also analyse a random `gas' of instantons. Using a set of simplifying approximations, we find a non-zero chiral condensate. However we also find that the spectral density diverges for small eigenvalues, so that the chiral condensate, at zero quark mass, diverges in quenched QCD. The degree of divergence decreases with the instanton density, so that it is negligible for the smallest number of cooling sweeps but becomes substantial for larger number of cools. We show that the spectral density scales, that finite volume corrections are small and we see evidence for the screening of topological charges. However we also find that the spectral density and chiral condensate vary rapidly with the number of cooling sweeps -- unlike, for example, the topological susceptibility. Whether the problem lies with the cooling or with the identification of the topological charges is an open question. This problem needs to be resolved before one can determine how important is the divergence we have found for quenched QCD.Comment: 33 pages, 16 figures (RevTex), substantial revisions; to appear in Phys.Rev.

Biased Metropolis Sampling for Rugged Free Energy Landscapes

Metropolis simulations of all-atom models of peptides (i.e. small proteins) are considered. Inspired by the funnel picture of Bryngelson and Wolyness, a transformation of the updating probabilities of the dihedral angles is defined, which uses probability densities from a higher temperature to improve the algorithmic performance at a lower temperature. The method is suitable for canonical as well as for generalized ensemble simulations. A simple approximation to the full transformation is tested at room temperature for Met-Enkephalin in vacuum. Integrated autocorrelation times are found to be reduced by factors close to two and a similar improvement due to generalized ensemble methods enters multiplicatively.Comment: Plenary talk at the Los Alamos conference, The Monte Carlo Method in Physical Sciences: Celebrating the 50th Anniversary of the Metropolis Algorithm, to appear in the proceedings, 11 pages, 4 figures, one table. Inconsistencies corrected and references adde

Stability Tests for a Class of 2D Continuous-Discrete Linear Systems with Dynamic Boundary Conditions

Repetitive processes are a distinct class of 2D systems of both practical and theoretical interest. Their essential characteristic is repeated sweeps, termed passes, through a set of dynamics defined over a finite duration with explicit interaction between the outputs, or pass profiles, produced as the system evolves. Experience has shown that these processes cannot be studied/controlled by direct application of existing theory (in all but a few very restrictive special cases). This fact, and the growing list of applications areas, has prompted an on-going research programme into the development of a 'mature' systems theory for these processes for onward translation into reliable generally applicable controller design algorithms. This paper develops stability tests for a sub-class of so-called differential linear repetitive processes in the presence of a general set of initial conditions, where it is known that the structure of these conditions is critical to their stability properties