University of Oxford, UK

A palaeontologist ponders how biodiversity is spread across the vertebrate tree of life.

Why do some biological groups burst at the seams with many different species, whereas others, despite their deep evolutionary heritage, contain only a handful of members? Many of my old vertebrate-biology textbooks are rife with qualitative scenarios, peddled with surprising degrees of confidence, that explain how species-rich branches can chalk up their success to key evolutionary 'innovations' and how less-diverse ones haven't kept up with changing conditions. What you won't find are details of how these exceptional groups might be identified in the first place.

Michael Alfaro of the University of California, Los Angeles, and his colleagues have now quantified this black art (Proc. Natl Acad. Sci. USA 106, 13410–13414; 2009). They marry statistically explicit models with fossil-calibrated evolutionary trees and counts of living species to ask a basic, but surprisingly unanswered question: precisely which branches of the vertebrate family tree are more or less species-rich than expected given their age?

The authors identify nine groups that show substantial changes from the background tempo of vertebrate evolution: 'living fossils' such as lungfishes are characterized by lower-than-predicted diversity, whereas other branches, such as the perch-like fishes and a subset of mammals, contain vastly more species than expected.

As a palaeontologist, I am intrigued that three of the exceptionally diverse radiations are thought (although not without controversy) to have proliferated following the mass extinction that killed off the dinosaurs, hinting at the far-reaching consequences of this event in structuring the modern vertebrate fauna. Most importantly, these authors establish a clear quantitative framework that can be used to test all those textbook stories. I'm confident that in a few years, my students will learn a much more nuanced picture of vertebrate diversification than I ever did, one that will trace its own roots back to studies such as this.

Posted on November 19, 2009 06:58 PM | Permalink | Comments (0) | TrackBacks (0)

University of California, San Francisco

A computational biologist looks at how mRNA length changes during development.

I am always amazed by how we start as a fertilized egg and develop into a complex, multicellular organism. This feat occurs despite the fact that the DNA in every cell — even the most specialized ones — remains, for the most part, unchanged.

One method of regulating gene activity in differentiated, or specialized, cells is through the messenger RNA (mRNA), the code of which is translated to make proteins. For example, proteins and other RNAs can bind to the untranslated regions (UTRs) at the 5' and 3' ends of mRNAs to regulate mRNA stability and translation.

The constitution of the 3' UTR itself can be regulated through alternative polyadenylation, whereby one of several possible UTR sites is cleaved, followed by the addition of adenosine-based molecules to its end. A broad shift in cleavage site choice — and thus 3' UTR length — during mammalian development was recently described by Bin Tian and his team at the University of Medicine and Dentistry of New Jersey in Newark (Z. Ji et al. Proc. Natl Acad. Sci. USA 106, 7028–7033; 2009).

By analysing genomic data, they show that 3' UTRs generally get longer during development and cell differentiation. The authors further show that most of the genes in which 3' UTRs are lengthened are also those that are increasingly suppressed during differentiation, such as the genes for DNA replication and cell division.

These findings bring to the forefront an underappreciated mechanism of genetic regulation that is likely to be important for normal cell differentiation. It is fascinating how many steps of the central dogma (DNA to RNA to protein) are controlled. This seems to be how evolution has managed to take a relatively simple cell and multiply it to form the complex body plan of the human.

Posted on November 13, 2009 07:38 PM | Permalink | Comments (0) | TrackBacks (0)

Leiden University, the Netherlands

A theoretical physicist journeys to a hairy black hole's horizon.

Rumour has it that Steven Spielberg is producing the ultimate science fiction movie, using state-of-the-art general-relativity simulations to create a realistic image of the warped space-time near a black hole. But wouldn't it be great to see such worlds in real life? In fact, you can: by extending your eyesight with 'AdS/CFT', a mathematical result of string theory that describes a 'through the looking-glass' experience that would embarrass the imagination of Lewis Carroll.

AdS/CFT states that information about the strange world of the black hole is, in a very indirect way, encoded in or 'imaged' by the properties of certain quantum-weird forms of matter. Scientists realized recently that these 'quantum critical' states of matter are routinely produced in condensed-matter laboratories. But a particular prediction of AdS/CFT made the string theorists nervous: the event horizon of the special black hole that is imaged by the quantum critical electrons seems to imply that the latter should show a macroscopic entropy at zero temperature. It has further been predicted that the black hole would be unstable and would eventually suck up 'stuff' from its surroundings, covering its horizon with 'hair' (S. A. Hartnoll et al. J. High Energy Phys. 2008, 015; 2008). In the electron system, out of the blue and at a quite low temperature, some unexpected order will set in that removes the ground-state entropy, giving it a unique ground state.

Intriguingly, I learned the other day that condensed-matter experimentalists, unaware of the string theorists' nervousness, are now in the grip of the same idea. The latest thermodynamic experiments on quantum-critical electrons are suggestive (albeit inconclusive) of a developing zero temperature entropy — for the experimentalists, a catastrophe — interrupted at a very low temperature by the onset of an exotic quantum liquid crystalline order (Z. Fisk Science 325, 1348–1349; 2009). It may be that we don't need spacecraft or Spielberg to visit black holes, just a little patience with the condensed-matter experimentalists.

Posted on November 5, 2009 10:17 PM | Permalink | Comments (0) | TrackBacks (0)

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.

Posted on October 29, 2009 08:13 PM | Permalink | Comments (0) | TrackBacks (0)

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 on October 23, 2009 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.

Posted on October 15, 2009 03:15 PM | Permalink | Comments (0) | TrackBacks (0)

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.

Posted on October 7, 2009 11:47 PM | Permalink | Comments (0) | TrackBacks (0)

Gladstone Institute of Cardiovascular Disease, San Francisco, California

A geneticist wonders why we need to sleep.

Scientists can have a love–hate relationship with sleep. We know that it is vital for our health, but not the reasons why. We celebrate dreams that provide inspiration, but often dismiss sleep as a chore.

Yet deep sleep can provide insight into vexing problems. In 1920, pharmacologist Otto Loewi famously had a recurring dream that suggested how he could demonstrate neurotransmission in the lab. The key experimental details escaped him until he captured the dream in a bedside notebook. Later that day, he performed his Nobel-prizewinning experiments with the aid of a few frog hearts and a water bath.

Now, a team led by Ying-Hui Fu reports that a single mutation in a gene called DEC2 can cause people to sleep for only about six hours per night instead of the usual eight (Y. He et al. Science 325, 866–870; 2009). This mutation seems to be exceedingly rare, with only two carriers found so far. Only by introducing this mutation into transgenic mice and fruitflies could the researchers show compelling evidence of the mutation's effect. These two additional waking hours each day are quite remarkable when you consider that, over 80 years, this would add up to more than 8 years of extra productivity!

Why are extreme short sleepers so rare? Surely evolutionary pressures should favour less sleep? In prehistoric times, short sleepers would have had more time to hunt, gather food and guard against predators. In modern society, we must constantly balance home, work and other demands. Sleep is often sacrificed, so a drug that could provide hours of extra productivity would be hugely popular.

A better understanding of the reasons for sleep could provide a rationale for getting more of it. In the meantime, I will keep a notebook by my bedside as a dream catcher.

Posted on September 30, 2009 08:18 PM | Permalink | Comments (2) | TrackBacks (0)