Francis Galton’s regression towards mediocrity and the stability of types

A prevalent narrative locates the discovery of the statistical phenomenon of regression to the mean in the work of Francis Galton. It is claimed that after 1885, Galton came to explain the fact that offspring deviated less from the mean value of the population than their parents did as a population-level statistical phenomenon and not as the result of the processes of inheritance. Arguing against this claim, we show that Galton did not explain regression towards mediocrity statistically, and did not give up on his ideas regarding an inheritance process that caused offspring to revert to the mean. While the common narrative focuses almost exclusively on Galton’s statistics, our arguments emphasize the anthropological and biological questions that Galton addressed. Galton used regression towards mediocrity to support the claim that some biological types were more stable than others and hence were resistant to evolutionary change. This view had implications concerning both natural selection and eugenics. The statistical explanation attributed to Galton appeared later, during the biometrician-mutationist debate in the early 1900s. It was in the context of this debate and specifically by the biometricians, that the development of the statistical explanation was originally attributed to Galton.     

An autonomous molecular computer for logical control of gene expression

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.     

The twisted ion-permeation pathway of a resting voltage-sensing domain

Proteins containing voltage-sensing domains (VSDs) translate changes in membrane potential into changes in ion permeability or enzymatic activity. In channels, voltage change triggers a switch in conformation of the VSD, which drives gating in a separate pore domain, or, in channels lacking a pore domain, directly gates an ion pathway within the VSD. Neither mechanism is well understood. In the Shaker potassium channel, mutation of the first arginine residue of the S4 helix to a smaller uncharged residue makes the VSD permeable to ions ('omega current') in the resting conformation ('S4 down'). Here we perform a structure-guided perturbation analysis of the omega conductance to map its VSD permeation pathway. We find that there are four omega pores per channel, which is consistent with one conduction path per VSD. Permeating ions from the extracellular medium enter the VSD at its peripheral junction with the pore domain, and then plunge into the core of the VSD in a curved conduction pathway. Our results provide a model of the resting conformation of the VSD.     

Detectable radio flares following gravitational waves from mergers of binary neutron stars

Mergers of neutron-star/neutron-star binaries are strong sources of gravitational waves. They can also launch subrelativistic and mildly relativistic outflows and are often assumed to be the sources of short γ-ray bursts. An electromagnetic signature that persisted for weeks to months after the event would strengthen any future claim of a detection of gravitational waves. Here we present results of calculations showing that the interaction of mildly relativistic outflows with the surrounding medium produces radio flares with peak emission at 1.4 gigahertz that persist at detectable (submillijansky) levels for weeks, out to a redshift of 0.1. Slower subrelativistic outflows produce flares detectable for years at 150 megahertz, as well as at 1.4 gigahertz, from slightly shorter distances. The radio transient RT 19870422 (ref. 11) has the properties predicted by our model, and its most probable origin is the merger of a compact neutron-star/neutron-star binary. The lack of radio detections usually associated with short γ-ray bursts does not constrain the radio transients that we discuss here (from mildly relativistic and subrelativistic outflows) because short γ-ray burst redshifts are typically >0.1 and the appropriate timescales (longer than weeks) have not been sampled.