Author Archives: Conor O'Brien

Oregon State University Genome Research and Biocomputing 2010 Conference Recap

This will be a quick post of some impressions from yesterday and today’s Center for Genome Research and Biocomputing (CGRB) Fall Conference at Oregon State University.  The speakers were uniformly high quality, with Peter and Rosemary Grant’s talk the consensus of highlight of the program.

Jay Dunlap, “Genetic and Molecular Dissection of a Simple Circadian System”

Dunlap works on the circadian clock in Neurospora, a filamentous fungi. Like the circadian clock in mammals and insects, the basis of the Neurospora clock is a heterodimer that autoregulates the transcription of its own genes.  This autoregulation gives rise to the daily rhythmic expression characteristic of a circadian clock.

Dunlap’s lab has done some hard-core molecular work to dissect the basis of this autoregulation.  This includes chromatin immunoprecipitation assays to demonstrate that methylation at the locus of a key circadian clock regulator is necessary to its proper function, a mutant screen that eventually demonstrated phosphorylation of a protein heterodimer was necessary for proper autoregulation and finally expression microarrays to look for peripheral elements of the circadian clock.  This is one of the better understood molecular genetic pathways, but Dunlap reminded us how much work remains.

My only criticism, which is really more of a difference in philosophies, is Dunlap’s reliance on mutagenesis.  There is natural variation in at least one Neurospora circadian phenotype; such genetic variation has an advantage over lab-induced mutations in that it is maintained by natural selection, whereas mutagenesis studies mostly produce phenotypes of large effect that would never survive in nature.  Natural variation, in a genetically tractable context, can thus be used to understand the molecular genetic basis of a phenotype and the environmental context which maintains it.

Richard Spinrad, “OSU Research Now, Next, and After Next.”

Spinrad discussed the present and future of academic research, with a focus on the need to better communicate science to the general public and to secure future sources of funding.  Most funding (about two thirds of OSU’s research budget by the look of his pie chart) comes from the federal government, while industry and non-profits made up another two percent each.  He discussed the need to make up for the expected federal research budget reductions.  One opportunity Spinrad mentioned is better partnerships with industry.  As corporations reduce in-house R & D, they may outsource it to universities.  There are significant issues with academic-corporate relationships that I won’t get into, but he’s basically right; basic research will need to find other sources of support and corporations will be one of those sources.

My take on his talk:  We’re all aware of the need to communicate our work more broadly and the likelihood of shrinking federal research budgets, but Spinrad didn’t have suggestions for how to address these problems besides attempting to give talks geared to a general audience when we’re traveling and finding ways to increase funding from industry and non-profit sources.  These ideas are both obvious enough to be useless without more detail.  I’m sure he’s been working on such ideas, I would like to have seen his talk include some.

Daniel Schafer, “Some Lessons from the Biometry of Evolution and the Evolution of Biometry.”

This was a, dare I say, entertaining talk about the history of statistics within evolutionary biology.  I only mention it for two points.  The first is that the speaker briefly mentioned the negative binomial-P distribution as a method for RNA-seq data analysis.  Who wants to host him for a potentially dry and very valuable seminar, such as this one?  Secondly, he and the moderator kept on referencing this video.

Peter and Rosemary Grant, “Evolution of Darwin’s Finches” The Roles of Genetics, Ecology and Behavior.”
The Grant’s long term (and ongoing!) data set of darwin finch evolution on Daphne Major is one of the most valuable scientific studies ever conducted.  They have documented evolution of beak size in response to environmental changes for several decades now (more detail available via Google, but a good source is here) and have recently described some of the genes responsible for this variation.  Data sets linking genetic changes to specific ecological changes are nearly impossible to produce.  This is one of the best.

The second part of the talk described incipient speciation driven by a stochastic event (the original PNAS paper is here).  The descendants of a hybrid male immigrant and a hybrid female bred exclusively with each other, producing a lineage with unique beak and body morphology.  The mechanism of this reproductive isolation was a new song, which appears to be the result of imperfect copying of the local species song by the initial hybrid male.  The reproductive isolation is maintained by his descendant’s learning this unique song from their father.  This accident of imperfect imitation leading to reproductive isolation illustrates how important such stochastic events can be to speciation.

As with the last time I saw them, the Grants ended with their thesis:  “To understand the diversity of species we see around us we need to understand the dynamic interactions between genetics, ecology and behavior.”  Their life’s work is the best evidence for this.

Embroidered data: needle & thread not required

We’re all familiar with examples of research misconduct (Marc Hauser being a prominent recent example), but there are plenty of other less deliberate and more insidious ways science can lie to itself.  These include publication bias, choosing a method of statistical analysis that gives the desired answer, etc.  Those are worth discussing, but this post will focus on an informative and (to me anyways) humorous example of embroidered data, which is when a series of misrepresentations of a data set build upon themselves, with the end result and the inferences drawn from it having little connection to reality.  I feel such embroidery happens easily as we filter the literature through our biases and limited abilities of retention.  Most examples may not be as egregious as the following, but they are still failures of science to regulate itself.

THE KAIBAB DEER (this figure is taken from Colvinaux’s 1973 textbook, “Introduction to Ecology.”)
The Kaibab plateau is an area bordering the Grand Canyon that had undergone a series of disturbances from fires, sheep and cattle grazing and finally, predator removal (which occurred after it was designated a park by Teddy Roosevelt).

A subsequent increase in the deer population (Figure 1a) was documented by Rasmussen’s 1941 monograph, “Biotic Communities of the Kaibab Plateau, Arizona.”  The apparent increase was attributed to the removal of top predators.  The solid circles represent the park supervisors’ estimates, the open circles represent those of visitors to the park.  A contemporary wildlife biologist would probably roll his or her eyes at either method, but common sense would suggest that supervisors, who spend far more time in the park, would give more accurate estimates.  At the least, both estimates are represented and their sources noted in Rasmussen’s original paper.

"The Kaibab deer herd fiction; a history of embroidered data. (A) Population estimate of the Kaibab deer herd, copied from Rasmussen (1941). Linked solid circles are the forest supervisor's estimates' circles give estimates of other persons, and the dashed line is Rasmussen's own estimate of the trend. (B) A copy of Leopold's (1943) interpretation of the trend. © A copy of trend given by David Davis and Golley (1963), after Allee et al. (1949), after Leopold (1943) from Rasmussen (1941). (After Caughley, 1970.)

Aldo Leopold (yes, that Aldo Leopold) started the real trouble by basing a publication figure on the curve drawn to fit the visitors’ estimates (Figure 1b).  Two problems should be apparent, 1) the second, and presumably more accurate estimate is ignored and 2) he only reproduced the fitted curve drawn by Rasmussen, which is obviously not an actual best-fit curve as it is drawn to intersect the maximum.   Furthermore, the shape of the curve is altered:  the left-hand side of Leopold’s curve has a sigmoid shape suggestive of a population undergoing logistic growth.  This is what we would expect of a population released from a key restraint.  The right hand side shows a sharp decrease, characteristic of a population that has exceeded its environment’s carrying capacity.  These alterations suggest that the ecological ideas Leopold wished to illustrate biased his interpretation and reproduction of the data.

Finally, Leopold’s modifications were codified in Allee’s 1949 ecology textbook, “Principles of Animal Ecology (click here for the original figure) (Figure 1c).  His comments on the figure thus became accepted fact, while the data they were originally based on is completely obscured.

This data set is still considered a classic example of the control exerted by predators on prey abundance, as Wikipedia demonstrates.

So what can we take from this example of embroidery?  In a narrow sense, predators do not control prey abundance as closely as is commonly thought, as habitat recovery and mitigation of other anthropogenic disturbances probably had a larger effect in the case of the Kaibab deer. (here’s a badly scanned pdf of the chapter I took the figure from if you want more information).

The larger point is obvious: “Look at the data,” to quote my adviser who first showed me this figure.  Science works best when methodology is transparent and a cautious, sound interpretation of the data is suggested.  It also means that we must read the original papers that are the basis of the theory or phenomenon that we’re investigating.  Just about every new grad student has had that point made to them, followed by enough demands to make such historical literature (as arcane and opaque as they often are) the first thing triaged, , but it is necessary if science is to successfully regulate itself.

Stepwide Modification of a Modular Enhancer Underlies Adaptation in a Drosophila Population

Stepwise Modification of a Modular Enhancer Underlies Adaptation in a Drosophila Population

Mark Rebeiz,1 John E. Pool,2,3 Victoria A. Kassner,1 Charles F. Aquadro,4 Sean B. Carroll1,*

Summary of paper
In Africa, drosophila dorsal abdominal pigmentation is correlated with altitude.  Ebony is a candidate gene for involvement in this phenotypic gradient, as it codes for an enzyme in a pathway that produces a tannish brown pigment.  A previous study (Pool and Aquadro 2007) produced evidence for a selective sweep at the ebony locus, further strengthening its potential as a candidate gene.  The goal of Rebeiz et al (2009) was to confirm that the ebony locus was responsible for this phenotypic variation and to determine the specific nucleotide variation causing it.

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