University of California, San Francisco

A biochemist looks at how DNA sequencing can reveal more than just sequences.

Huge advances in DNA sequencing have allowed us to readily determine the sequence of almost any living (and a few extinct) species. Yet arguably, most biological insight comes from work on five model organisms: Escherichia coli, baker's yeast, roundworms, fruitflies and mice. Unfortunately, many important biological processes are not captured in these creatures.

Papers from two groups, one led by Andrew Camilli of Tufts University in Boston, Massachusetts, the other by Brian Akerley at the University of Massachusetts in Worcester, describe new genetic tools that allow the quantitative dissection of gene function in a wide range of microorganisms (T. van Opijnen et al. Nature Methods 6, 767–772; 2009; and J. D. Gawronski et al. Proc. Natl Acad. Sci. USA 106, 16422–16427; 2009). These studies combine exhaustive transposon mutagenesis — whereby thousands of small DNA segments, or transposons, are introduced into the genome to mutate many genes — with massively parallel, or 'deep' sequencing of transposon/chromosome junctions to monitor the consequences of the loss of single or pairs of genes on the organisms' traits.

The real power of the approaches comes from the deep sequencing, which tracks the abundance of individual transposon mutants after they have been subjected to a stress. Knowing by how much each mutant has grown or suffered under the stress provides a measure of the relative roles that the mutated genes have.

I find it particularly gratifying that the advances in deep sequencing that have allowed us to catalogue so many genes from so many organisms can now be harnessed to help us figure out what these genes actually do.

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University of East Anglia, UK and the British Antarctic Survey

An oceanographer marvels at the good timing of shrimp.

For many marine organisms, the timing of egg hatching is key to species survival because the time window in which larvae can survive is very short. If eggs hatch too early, they starve before their food source — the spring phytoplankton — blooms. If they hatch too late, they also miss the bloom.

I'm amazed by how often nature gets things right. In most of the North Atlantic, shrimp eggs hatch just a few days before the spring bloom. Peter Koeller of the Bedford Institute of Oceanography in Dartmouth, Nova Scotia, showed that the development and hatching time of shrimp are influenced by local deep-ocean temperature (P. Koeller et al. Science 324, 791–793, 2009). This is not surprising, because eggs develop in the deep ocean and their growth rate depends on temperature.

What is surprising is that the shrimp spawn on the right day of the year across the North Atlantic, even though temperatures in the deep ocean vary from one area to the next and do not influence the timing of the spring bloom. Through evolution, the shrimp have adapted to local temperature patterns to spawn at just the right time.

However, this could prove to be a problem for shrimp and the many other zooplankton, fish and shellfish species that have adapted their spawning habits to local conditions. What will the survival rate of larvae be if deep-ocean temperatures rise, or if the spring bloom occurs earlier? How much time do organisms need to sense and adapt to such changes? These new data will help us to understand the complex interdependence of marine ecosystems, and possibly help to detect potential mismatches between egg hatching and food-source availability.

Posted by Corie Lok at 09:50 PM | Permalink | Comments (0) | TrackBacks (0)

Princeton University, New Jersey

A neuroscientist explores the energy efficiency of the brain.

Considering its substantial processing capacity, the human brain consumes remarkably little power — about as much as an idling laptop computer. So I was interested to learn that action potentials — the electrical 'spikes' that are the fundamental units of neuronal activity — are likewise remarkably energy efficient (H. Alle et al. Science 325, 1405–1408; 2009).

During a spike, the voltage across a neuron's membrane is reversed when sodium ions flow into the cell and potassium ions move out. This reversal spreads as a wave down the neuron's axon towards its terminals, where it triggers synaptic transmission to other neurons.

Henrik Alle of the Max Planck Institute for Brain Research in Frankfurt, Germany, and his colleagues recorded charge movements at axon terminals in mammalian hippocampal neurons. They found that sodium and potassium ions flow at largely non-overlapping times, with more than 75% of all charge contributing unopposed to the rise or fall of a spike.

Such efficiency comes as a surprise. These axons outperform the much-studied squid giant axon by a factor of three. If the findings apply to other mammalian neurons, brain tissue may support more firing than suspected. The authors suggest that synaptic transmission may dominate the energy budget of brain tissue.

These results have implications for functional magnetic resonance imaging, which measures increases in blood oxygenation in the brain as an indicator of neural activity. What causes the blood-oxygen boost is unknown: suggested triggers include synaptic transmission and action potentials. This paper is evidence for the former, because energy-intensive events such as synaptic signalling are more likely to be oxygen-hungry and to stimulate blood flow. The idea is supported by other recent evidence — a wonderful convergence.

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Edward Grey Institute, Department of Zoology, University of Oxford, UK

An evolutionary biologist compares genomic complexity to modern art.

Like many students of evolutionary biology, I was taught that genes encode physical traits, or 'phenotypes', that are the focus of natural selection — a model with clear, direct links and few, if any, complications. Over the past few years, I have found it increasingly difficult to reconcile this simple model connecting genes and the organisms they encode with the burgeoning data of systems biology, which show the genome as a heaving tangle of interconnections. Given the complexity of the genome, how can selection target any single gene without unintended consequences?

Trudy Mackay at North Carolina State University in Raleigh and her collaborators have begun to resolve the opposing genomic and evolutionary world views by examining the systems genetics that underlie phenotypes in the fruitfly Drosophila melanogaster (J. F. Ayroles et al. Nature Genet. 41, 299–307; 2009). They do this by comparing data on the abundance of more than 10,000 DNA transcripts with whole-organism traits, such as fitness and lifespan, in 40 fruitfly lines.

The researchers show that aggregates of genes correlate with distinct characteristics in flies, and that these modules are connected, with groups of genes associated with multiple phenotypic traits. This elegant complexity is best conveyed by the figures in the paper, some of which look as though they were lifted off the walls of a modern-art gallery.

The group's work provides a post-genomic framework for dissecting the intricate underpinnings of organismal biology. More importantly, the paper demonstrates that key topics in traditional evolutionary studies, such as heritability, and more recent concepts, such as pleiotropy (whereby one gene affects multiple traits), are related. As such, they must be considered together to build a complete understanding of how selection acts through the phenotype to sculpt the genome.

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