In focus: New genetic method proves the importance of wing geometry in ‘superflies’.

What defines the biomechanical performance of an animal? Dr Robert Ray (Francis Crick Institute), in collaboration with Dr Richard Bomphrey’s group at the Royal Veterinary College have just published their findings that by altering the production of just one protein they can change – and even improve – flight agility in fruit flies. This ground-breaking study is the first to use this method to objectively study what affects animal performance during locomotion.

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The model organism Drosophila melanogaster offers biologists the opportunity to target specific genes in specific body regions during development.

Unlike bats and birds, insects have relatively little control over their wing shape during flight and so cannot dramatically change their aerodynamic properties ‘on-the-fly’ but wing shape is extremely important to both agility and efficiency. The shapes we see in most species, therefore, represent a trade-off between these attributes. Energetic economy is obviously very important, but increased agility could make the difference between life and death when encountering a predator. During the last century, several genes have been identified which affect wing development in the fruit fly Drosophila melanogaster without changing the patterning: altering length, width, asymmetry and other geometric features. These clearly have the potential to substantially change the performance of the flies, but the precise mechanisms have remained unclear until now.

Identifying the factors driving differences in performance can be highly challenging: for example, a runner with longer legs might be faster, but this could be the result of longer strides, greater muscle mass or greater torque around the joints. This is further complicated by the low signal-to-noise ratios of some biomechanical experiments, which make it hard to distinguish meaningful physiological differences in ability from behavioural variations or other confounding effects. As a result, disentangling the exact causes has always been a significant challenge in biomechanics, particularly in a process as complex as flight. Where researchers have tried to study wing shape in the past knock-on effects from physical or genetic interference have hampered efforts to have fully controlled experiments, but Ray and his colleagues developed a new method to establish the effects of selected individual traits including narrow, a gene which controls wing shape. Flies lacking narrow have unusually pointed wings compared to wild types.

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Some examples of variation in wing shape in the animals raised by Ray and colleagues, which fall into four main groups. From Ray et al. 2016.

RNA interference, or RNAi, is a technique used to decrease the expression of a specific gene by introducing tailor-made molecules into cells which bind to the transcripts of the gene before they can be translated into proteins. This activates cellular machinery which then targets the transcripts for destruction, so the protein is never produced. Unlike ‘knocking out’ genes from the genome, RNAi can be applied at specific locations, levels or points during development to reduce expression without inadvertently changing any other traits.  The researchers used RNAi to knock down the expression of narrow in only the wings, and only during their development, so that there were no effects on any other aspect of the flies. Different levels of intervention produced four different groups of adult flies: a control group, which were no different from wild type individuals, an extreme morph with very pointed wings, and two intermediate groups.

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The movements of flying subjects were tracked digitally to analyse their speed, acceleration and manouevrability. From Ray et al. 2016.

The team tracked the movements of the flies using high-speed video (above) and examined their velocity, acceleration and manoeuverability. As expected, peak and modal speeds and acceleration were unaffected, as the flight muscles and machinery were unchanged. The most extreme narrow morphs were less agile than all three other groups, but, to the team’s surprise, the two intermediate groups of flies displayed increased agility compared to the controls; they turned faster and tighter corners. Further analysis shows that these groups were also less efficient, demonstrating that the method had successfully tipped the balance between agility and efficiency. But the extreme wing morph was too different for the flight system to cope with, and performance suffered.

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Intermediate wing shapes could further and faster than control flies and those with extreme wing morphs. From Ray et al. 2016.

This is the first time the biomechanical effects of a single gene have been successfully isolated for study, and it will likely lay the blueprint for many more projects in the future. It not only exemplifies the balance between agility and efficiency, but it shows that there is room for improvement in one or both of these in the fruit fly. For Bomphrey and his team, this is an exciting step towards understanding performance trade-offs, evolutionary biology and the direct causal relationships between genetic traits and biomechanical performance effects.

Interested? You can read the original paper here

Glossary

RNA interference: Introducing artificial RNA into a cell to alter gene expression. By designing RNA molecules which will bind to specific mRNAs (see below), researchers can tag these mRNAs for destruction by the cell itself, thus reducing the expression of the gene.

Signal-to-noise ratios (SNRs): The strength of a genuine pattern against a background of non-relevant interference. For example, shouting in a quiet room would give a high SNR and be easy to hear, but whispering in a busy room would be much harder to detect due to the low SNR.

Transcripts: mRNA ‘copies’ of genes. When a gene is expressed, the cell reads one of the DNA strands and builds a ‘carbon copy’ of the sequence using RNA (similar to DNA). This messenger copy (mRNA) travels out of the cell nucleus, where most cellular DNA is kept, and is then read by ribosomes which build the encoded protein.

Images courtesy of Richard Bomphrey, Marco Teixeira de Freitas.

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