Dangerous scientists?

June 28, 2010

The Guardian UK Science Blog has a interesting report on a recent European survey on public attitudes towards science. The Eurobarometer survey for the European Union found that hearteningly, 80% of Europeans are interested in science, but somewhat more worryingly, that 53% think scientists are “dangerous” .  Scientists from universities and government organisations were more likely to be regarded as qualified to explain scientific and technological developments than either scientists working in industry or newspaper journalists.  The survey also found that a majority of people think that scientists don’t put enough effort into informing the public about new developments in science.

The full article is here.

Quote on exploratory research

June 23, 2010

I just came across this quote from Marie Curie on Christie Wilcox’s blog, Observations of a Nerd, which I thought followed on quite nicely from the recent TED talk I posted about on the benefits of exploratory research.

“We must not forget that when radium was discovered no one knew that it would prove useful in hospitals. The work was one of pure science. And this is a proof that scientific work must not be considered from the point of view of the direct usefulness of it. It must be done for itself, for the beauty of science, and then there is always the chance that a scientific discovery may become – like the radium – a benefit for humanity.” – MARIE CURIE

Tuatara holds clues to human evolution

June 16, 2010

ResearchBlogging.orgA while ago I wrote about the value of genome sequences, not just for helping us understand the biology of a particular organism, but also for enabling large-scale comparisons across species that can help spot patterns in genome evolution which wouldn’t otherwise be apparent.  A recent paper in Journal of Heredity by Craig Lowe, David Haussler and colleagues at the University of California provides an excellent example of this in action, using sequences from the tuatara genome to identify the evolutionary origin of parts of the human genome.

Lowe and colleagues were looking for functional elements (like parts of genes and their regulatory regions) in the human genome that originated from retrotransposon insertions.  Retrotransposons are mobile bits of DNA that have a tendency to make copies of themselves and insert themselves in various different places in the genome.  They contain everything needed for this copying, plus often include functional modules like exons of genes, or transcription factor binding sites.  These functional modules may be co-opted for a new function in the new site, a process known as exaptation.  Once a retrotransposon is inserted in a new location it is often inactivated, and then begins to accumulate mutations which render it unrecognisable as a retrotransposon. This makes it difficult to identify exaptation events in any given genome and hence trace the origin of many of the functional elements of that genome.  However, by comparing the genomes of many different species in different lineages it may be possible to identify ancestral versions of these elements, and so trace their evolutionary history.

Lowe and colleagues found a previously unknown retrotransposon in the small part of the tuatara genome that has been sequenced.  This retrotransposon is of a type known as a LINE – Long Interpersed Nucleotide Element – and was named EDGR-LINE  (endangered-LINE).  A search of human genome against this sequence found 18 elements that are likely to be the result of insertion of this retrotransposon into the genome at some point in evolutionary time.  Seventeen of these elements are gene regulatory regions and one is an exon of a gene called ASXL3.  ASXL3 is important for regulation of other genes during development and the additional exon co-opted from EDGR-LINE appears to help control its expression.

These 18 exaptation events likely occurred early in mammalian evolution, but the retrotransposon itself has long since been inactivated in humans so all traces of it have been lost.  The functional elements it contained are able to be identified because they are under strong purifying selection (i.e. have not accumulated many mutations), so can still be aligned with the tuatara sequence.  Its only through this comparison that it is possible to know that these 18 elements originated from the same retrotransposon.

EDGR-LINE was also found in the lizard, frog, and coelecanth, but no traces of it remain in mammals, crocodylia and birds.  EDGR-LINE appears to be more slowly evolving in tuatara than in lizards, so is closest to the mammalian ancestral version of EDGR-LINE and hence more informative for identifying elements in the human genome. In fact, 10 of the 18 elements could only be identified by comparison with tuatara and not with these other species.

Evolution of the EDGR-LINE in vertebrates. The EDGR-LINE appears to have been introduced in the common ancestor of tetrapods and lobe-finned fish, and lineages where the LINE was active are shown with green. The LINE is not noticeable in mammals, crocodylia, aves, or testudines, so it has already been inactivated at least twice in evolution.

This is not the only example of genomic information from a rare species shedding light on the evolutionary history of human genome.  The genome of the threatened desert tortoise Gopherus agassizii also harbours an ancient LINE that has enabled functional elements of the human genome to be identified.  Lowe and colleagues speculate that this may be due to the very nature of endangered species, and ran simulations to show that theoretically, mobile elements like LINEs are active for longer and evolve more slowly in small populations.   This effect comes about because of the relationship between population size and selection – selection is more efficient in large populations so is more likely to remove genetic variants which are mildly harmful (or deleterious) to the organism, and to fix mutations which are beneficial.  The smaller the population, the more likely it is that deleterious genetic variants will become fixed in that population and beneficial mutations will be removed.  Insertion of mobile elements into new places in the genome is almost always deleterious, as it messes with existing genes and their regulatory regions.  Thus small populations will be more likely to accumulate additional copies of the mobile elements, and less likely to accumulate mutations which would remove or inactivate them.  I should point out here that tuatara are not actually classified as endangered (as the paper claims), but they have had a historically low population size, with probably a severe population bottleneck during the oligocene inundation of the New Zealand land mass.  In addition, we now know that even large tuatara populations can have a small effective population size, as few individuals actually contribute to mating at any one time.

Lowe and colleagues point out that without the tuatara, we would not have been able to identify these particular functional elements in the human genome, and that we never know what additional information about human evolution we might glean from threatened species in the future.  This underscores the importance of projects like the Genome10K initiative to sequence 10,000 vertebrate genomes.  Of course I would add that we should preserve these species for their intrinsic worth not just because of what they can tell us about human evolution, but this paper does highlight the unexpected ways that genomic data from diverse species can help us understand evolution.

Lowe, C., Bejerano, G., Salama, S., & Haussler, D. (2010). Endangered Species Hold Clues to Human Evolution Journal of Heredity DOI: 10.1093/jhered/esq016

A plea for exploratory research

June 8, 2010

On more than one occasion I’ve been asked what the commercial applications of my research are, usually by people who have no background in science themselves. When I tell them I do basic research in evolutionary genetics that doesn’t have any commercial application there often follows outrage that the government actually gives out money to pursue this research (and of course I would argue that there isn’t nearly enough funding to do this type of research).

In this TED talk, Brian Cox makes the case for curiosity-driven research.  Although his examples come from physics and astronomy, there are countless similar examples in biology.  I particularly like the quote from British chemist and inventor Humphrey Davy that he ends with:  “Nothing is more fatal to the progress of the human mind than to presume that our views of science are ultimate, that our triumphs are complete, that there are no mysteries in nature, and that there are no new worlds to conquer.”

In tough economic times, our exploratory science programs — from space probes to the LHC — are first to suffer budget cuts. Brian Cox explains how curiosity-driven science pays for itself, powering innovation and a profound appreciation of our existence.

An interview with Rebecca Cann of Mitochondrial Eve fame

June 1, 2010

In 1987, Rebecca Cann, Mark Stoneking and the late Allan Wilson published a paper in Nature showing that all human females can trace their lineage back to a single maternal ancestor (“mitochondrial Eve“) located in Africa.  In Plos Genetics this week there is an interesting interview with Rebecca Cann, where she talks about her own history and the research behind the mitochondrial Eve hypothesis.

In unearthing the genetic history of human populations, the recent pace of discovery has been so rapid that we can lose sight of the impact made by a single paper. In a 1987 Nature article, Rebecca Cann and her co-workers, Mark Stoneking and the late Allan Wilson, painstakingly analyzed mitochondrial DNA purified from placentas that had been collected from women of many different ancestral origins. By comparing the mitochondrial DNA variants to each other, the authors produced a phylogenetic tree that showed how human mitochondria are all related to each other and, by implication, how all living females, through whom mitochondria are transmitted, are descended from a single maternal ancestor. Not only that, they localized the root of the tree in Africa. The report left a wake, still rippling today, that stimulated not just geneticists and paleo-anthropologists, but the layperson as well, especially as the ancestor was quickly dubbed “Mitochondrial Eve.”

For the full interview, see Gitschier J (2010) All About Mitochondrial Eve: An Interview with Rebecca Cann. PLoS Genet 6(5): e1000959. doi:10.1371/journal.pgen.1000959