The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci and the genome-wide patterns of polymorphism show signatures consistent with frequent po
sitive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most apparent genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked recurrent deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1,000 Genomes project (Abecasis et al. 2012) and detect signatures of pervasive positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as the presence of unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to show that the observed signatures require a high rate of strongly adaptive substitutions in the vicinity of the amino acid changes. We further demonstrate that the observed signatures of positive selection correlate more strongly with the presence of regulatory sequences, as predicted by ENCODE (Gerstein et al. 2012), than the positions of amino acid substitutions. Our results establish that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson (King and Wilson 1975) that adaptive divergence is primarily driven by regulatory changes.
In order to stabilize the behavior of noisy systems, confining it around a desirable state, an effort is required to suppress the intrinsic noise. This noise suppression task entails a cost. For the important case of thermal noise in an overdamped sy
stem, we show that the minimum cost is achieved when the system control parameters are held constant: any additional deterministic or random modulation produces an increase of the cost. We discuss the implications of this phenomenon for those overdamped systems whose control parameters are intrinsically noisy, presenting a case study based on the example of a Brownian particle optically trapped in an oscillating potential.
The Photonic Force Microscope (PFM) is an opto-mechanical technique based on an optical trap that can be assumed to probe forces in microscopic systems. This technique has been used to measure forces in the range of pico- and femto-Newton, assessing
the mechanical properties of biomolecules as well as of other microscopic systems. For a correct use of the PFM, the force field to measure has to be invariable (homogeneous) on the scale of the Brownian motion of the trapped probe. This condition implicates that the force field must be conservative, excluding the possibility of a rotational component. However, there are cases where these assumptions are not fulfilled Here, we show how to improve the PFM technique in order to be able to deal with these cases. We introduce the theory of this enhanced PFM and we propose a concrete analysis workflow to reconstruct the force field from the experimental time-series of the probe position. Furthermore, we experimentally verify some particularly important cases, namely the case of a conservative or rotational force-field.
We suggest an approach to microrheology based on optical traps in order to measure fluid fluxes around singular points of fluid flows. We experimentally demonstrate this technique, applying it to the characterization of controlled flows produced by a
set of birefringent spheres spinning due to the transfer of light angular momentum. Unlike the previous techniques, this method is able to distinguish between a singular point in a complex flow and the absence of flow at all; furthermore it permits us to characterize the stability of the singular point.
