University of Helsinki, Finland

A statistician wonders about the influence of additive variance

Where complex problems are concerned, it makes things simpler if some factors can be safely ignored. In quantitative genetics, one such assumption is that the bulk of genetic variation is additive. That is, the effect of an allele — a particular version of a gene — can be adequately described by its average effect in a population. But we know that genes often do not act additively; alleles interact, both with others of the same gene (a phenomenon known as dominance) and those of different genes (epistasis). All this contributes to the total genetic variation. But does this matter?

This question is tackled by Hill et al. (PLoS Genet. 4, e1000008; 2008). Reviewing the literature, they show that additive genetic variance is often close to total genetic variance. The authors then look at some mathematical models with strong non-additive genetic effects, and average over reasonable distributions of allele frequencies to show that the genetic variance is mainly additive. So non-additive genetic variation is usually of minor significance and we can continue to concentrate on additive genetic variance.

This is probably true on average, but may not always be so. Any trait is affected by only a finite, and in some cases small, number of genes. So averaging over all possible allele frequencies may say little about a particular case. There is also a much subtler problem. The authors conclude that additive genetic variance swamps other types of variation largely because most alleles common to a population occur with close to 100% frequency. But these extreme frequencies also reduce the total genetic variance. So, in practice, a lot of traits with strong additive effects might be classified as having no detectable genetic variation, and overall the importance of additive genetic effects would be diminished. Is this a genuine problem? Ah, more research is obviously needed.

Posted by Anna Petherick at 04:32 PM | Permalink | Comments (1) | TrackBacks (0)

Harvard Medical School, Boston, Massachusetts

A signalling scientist marvels at perfect patterns

The formation of patterns during animal development depends to a great extent on cells, or groups of cells, sending a specific signal that activates a cascade of reactions in the cells that receive and respond to it. Studies of this process in the fruitfly Drosophila have provided many insights into the nature of the molecules involved and the mechanisms underlying cell–cell signalling.

The cell surfaces of almost all animals are decorated extensively with large molecules known as heparan sulphate proteoglycans (HSPGs). These modulate most developmental signalling pathways and comprise protein cores modified by the addition of long carbohydrate chains called glycosaminoglycans (GAGs). GAGs are key to mediating interactions between HSPGs and the molecules that they bind.

Recently, Rahul Warrior at the University of California, Irvine, and his colleagues (Development 135, 1039–1047; 2008) explained the puzzling observation that although HSPGs are required for signalling by the protein BMP in certain tissues, they are not required for BMP signalling during very early fly development.

The authors demonstrate that GAG synthesis does not occur in early embryos because the messenger RNAs that encode two enzymes involved in its construction are not translated.Preventing GAG synthesis at this stage allows an 'activity gradient' of BMP to be generated across the embryo that patterns the dorso–ventral axis of the fly. A few hours later, the GAG enzymes are produced, allowing the modified HSPGs to participate in other signalling pathways.

This study illustrates how temporal control of the synthesis of a ubiquitous set of enzymes is used to modulate the activity of signalling pathways in different tissues.

Posted by Anna Petherick at 04:28 PM | Permalink | Comments (2) | TrackBacks (0)

Queen's University, Belfast, Northern Ireland

A chemist looks at DNA-based molecular logic

Logic gates — AND, OR and NOT gates — are used in all manner of electronic devices, for example computers, in which they are connected in huge arrays. Several research groups, including my own, have designed and built molecular logic gates since the early 1990s. But the usefulness of our efforts has been limited because linking these gates in series has proved difficult.

Recently, Reza Ghadiri and his colleagues at the Scripps Research Institute in La Jolla, California, constructed a full set of logic gates that release a single-stranded DNA sequence when provided with the correct combination of single-stranded DNA inputs (B. M. Frezza et al. J. Am. Chem. Soc. 129, 14875–14879; 2007). This means that the output of one gate can be the input for another, and that the gates can be 'wired together' into multi-level circuits using the solution containing the DNA as a communication medium.

The gates work as follows. When a single strand of DNA pairs with a longer strand, an 'overhang' of unpaired DNA is left. If another complementary strand then comes along that is the same length as the longer strand, the overhang provides a foothold, allowing the new strand to push the shorter one off and form a full-length hybridized pair. Ghadiri et al. attached the DNA to beads so that different gates could be kept apart until the correct input was ready. They also added a fluorescent part to the final output signal to make the result easy to monitor.

This may not seem like much of an achievement to a computer buff. Nevertheless, I think the principle that this paper describes could pave the way to more useful molecular logic gates. In the meantime, the simple molecular logic gates that are available can serve in real-life applications such as identification tags for small micrometric objects. Semiconductor identification devices are too big for this purpose.

Posted by Anna Petherick at 04:25 PM | Permalink | Comments (0) | TrackBacks (0)

Weizmann Institute of Science, Rehovot, Israel

A physicist applauds evidence for the quantum spin Hall effect

I have been fascinated by the ballistic (collisionless) motion of charge carriers in solids since the start of my career. In practice this motion is often impeded by unavoidable impurities in the solid. But when it works, the charge carriers maintain their quantum properties while dissipating a minimum amount of energy.

Applying a strong magnetic field perpendicular to a two-dimensional conducting layer can accomplish the feat. Then, the quantum Hall effect kicks in, forcing the charges to the edges of the sample where they skip along in so-called 'chiral edge channels'. Backward scattering is virtually eliminated because that would require the charges to find a way to the opposite edge, where charges move in the opposite direction.

Recently, Laurens Molenkamp of the University of Würzburg in Germany and his colleagues took a step towards verifying the quantum spin Hall effect (M. König et al. Science 318, 766–770; 2007). This is where chiral edge channels form spontaneously in semiconductor insulators with peculiar electronic structures — namely, where the valence band is energetically higher than the conduction band because of the strong spin-orbit interaction between electron spins and electron velocities. This means that spin-up electrons are carried only by edge channels moving in one direction and spin-down elections are carried by edge channels moving in the opposite direction.

Molenkamp's team used a thin layer of mercury telluride sandwiched between two layers of mercury cadmium telluride. Because measuring spin current is difficult, they recorded the conductance of this middle layer to verify the ballistic transport that characterizes edge-channel transport. It was quantized, as predicted.

With further verification, the finding could lead to low-power devices based on the transport of spins rather than charges. Thus a quirk in the scientific field I have always loved might find a practical application.

Posted by Anna Petherick at 04:06 PM | Permalink | Comments (0) | TrackBacks (0)