Thursday, May 31, 2007


Gordon Holmes of Scotland has made a video of something in the Loch Ness. There's an article and another video at CNN.

"I couldn't believe my eyes when I saw this jet black thing, about 45-feet long, moving fairly fast in the water," said Gordon Holmes, the 55-year-old a lab technician from Shipley, Yorkshire, who took the video this past Saturday."

"My initial thought is it could be a very big eel, they have serpent-like features and they may explain all the sightings in Loch Ness over the years."

Perhaps it is a fake video. Perhaps it is real. Whatever it is, it is big and moving fast. Post a comment with your favorite hypothesis.

Ten Simple Rules...

PLoS Computational Biology has a number helpful papers for navigating the science world, from getting published, to getting grants, to making presentations. My Biotech Life has collected them all here.

Wednesday, May 30, 2007

Colors of the World

Currently I'm reading Evolution: A Scientific American Reader, a collection of articles on astronomy, cell biology, paleontology and anthropology from the print magazine. One of my favorite chapters, "Skin Deep" by Nina Jablonski and George Chaplin, covers the evolution of human skin color.

Skin color results from the presence of the pigment melanin, an organic molecule that absorbs UV radiation and neutralizes free-radicals produced by UV radiation. Why do we need worry about UV radiation? UV radiation causes mutations in skin cells leading to skin cancer, and also destroys the essential B vitamin, folate, which is involved in DNA synthesis. The more melanin, the more protection against UV radiation and the darker the skin.

Hmm, well ok then, if that is the case, why do not all humans have dark skin? Better to protect against cancer then, isn't it? The answer is that UV light also has another effect: it activates 7-dehydrocholesterol into vitamin D3. Too much melanin will therefore lead to vitamin D3 deficiency. This isn't much of a problem in the tropics where there is plenty of sunlight, but can be a issue at the margins of the world where sunlight is reduced. There are two competing forces, then, affecting human skin tone: the need to protect against cancer and the need for vitamin D3.

The interesting thing is that humans have evolved to carefully regulate the amount of UV light penetrating the skin, and hence carefully balancing the trade-off between vitamin D3 and cancer. A recent review reports that skin reflectance is lowest (i.e. melanin is highest) at the equator, then gradually increases, about 8% per 10° of latitude in the Northern Hemisphere and about 4% per 10° of latitude in the Southern Hemisphere. This pattern is inversely correlated with levels of UV irradiation, which are greater in the Southern than in the Northern Hemisphere.

There are, of course, exceptions to the rule, but these are informative in their own right. For example, the Inuit natives of the arctic are dark-skinned. This can be explained by the fact that their traditional animal-based diet provides plenty of vitamin D3. Another example is the difference in skin color between the dark skinned Bantu and light skinned Khoisan inhabiting Southern Africa. It poses a puzzle unless one considers that the Khoisan are derived from one of the earliest migrations into Southern Africa, whereas the Bantu migrated from West Africa more recently, perhaps within the past 1000 years.

Jablonski and Chaplin end their essay by writing, "Our current knowledge of the evolution of human skin indicates that variations in skin color, like most of our physical attributes, can be explained by adaptation to the environment through natural selection. We look ahead to the day when the vestiges of old scientific mistakes will be erased and replaced by a better understanding of human origins and diversity. Our variation in skin color should be celebrated as one of the most visible manifestations of our evolution as a species."

Think about that while you are out tanning this summer...

Read more about skin color here.

Figure from Barsh GS (2003) What Controls Variation in Human Skin Color? PLoS Biol 1(1): e27 doi:10.1371/journal.pbio.0000027. A traditional skin color map based on the data of Biasutti. Reproduced from with permission from Dennis O'Neil.

I Don't Believe in the Triassic Either...

This just in from the America's Finest News Source: The Onion.

"Everything about the Triassic period points to divine involvement. Let me ask you this: Could some kind of random genetic chance make the population of shelled cephalopods grow significantly? No, of course not. So the only logical explanation is that there was an infinite and all-knowing cephalopod creator who modified their mollusk foot into a muscular hydrostat that eventually, on the sixth day, became a tentacle."

Monday, May 28, 2007

Botany 2.0

The Missouri Botanical Garden Library has a really neat website, is a freely accessible, Web-based archive of beautifully illustrated volumes from the 18th and 19th century botanical literature. The best thing about is that it fully embraces 21st century web technology, such as tag clouds, map mashups, and even an RSS feed for new additions. Also all the images are free for non-commercial use, as long as you abide by the terms set down in the Creative Commons Attribution-Noncommercial 2.5 license.

Sunday, May 27, 2007

Brain Worms, Parasitic Fungi and Other Evilutionary Wonders

Evilutionary biologists such as myself thoroughly appreciate the diversity of life and love organisms of all kinds, but parasites are our favorites. David Sloan Wilson is enamoured of the brain worm (i.e. the Lancet liver fluke, Dicrocoelium dendriticum). Toxoplasma gondii is the official mascot over at the Loom. Richard Dawkins seems to take untoward delight in describing the Ichneumonidae (see also here). My favorite are the parasitic fungi, Cordyceps spp. Here's an entertaining blog post about Cordyceps and ants (plus special bonus, the hairworm Spinochordodes tellinii). What's not for an evilutionary biologist to love?

Saturday, May 26, 2007

Better to Give than to Receive

One of the great mysteries of evolutionary biology is altruistic behavior. Why should organisms reduce their own fitness for the benefit of others? For example, social grooming (depicted) appears to have no direct benefit for the groomer. The standard explanations cite reciprocity (i.e., I'll pick the nits off your back, if you pick the nits off mine) and social enhancement (e.g., alliance building). What's not often considered is the possibility that the behavior is directly beneficial for the actor, and that's exactly what a new paper by Shutt et al. in Biology Letters suggests. "In this study, we quantified grooming behaviour and physiological stress (assessed by faecal glucocorticoid analysis) in free-ranging Barbary macaques, Macaca sylvanus. Our results indicate that it is the giving rather than the receiving of grooming that is associated with lower stress levels."

Of course, I say! No wonder we find petting our pets so enjoyable and relaxing. It probably simulates social grooming and reduces our stress hormones.

Photo by Crystalline Radical.

Friday, May 25, 2007

Human Bacterial Communities

There's a neat article in Science News Online covering recent research on the microbial communities inhabiting the body's major niches. It is becoming more and more apparent that your microbial community plays an important role in your health and well being. Currently the National Institutes of Health is pondering the question of whether to devote resources to a Human Microbiome Project, which would create a genetic inventory of the microbial communities inhabiting the body. Jonathan Eisen at the Tree of Life posted on the Human Microbiome earlier this year.


NIH Roadmap - The Human Microbiome Project approved!

Photo credit:

In the gastric mucosa of a patient with Helicobacter pylori infection and a precancerous lesion called "incomplete intestinal metaplasia" (Genta stain), the gastric cells lining a gland have been replaced by absorptive intestinal cells with visible brush border and goblet cells, which are normally present in the intestine, but not in the stomach. Goblet cells contain acidic mucins stained blue by Alcian blue. This type of precancerous transformation is caused by long-term infection with H. pylori, visible in the lumen of the gland as curved bacterial rods stained black by silver stain. A few bacteria invade the goblet cells and can be found within blood capillaries, where they bind to red blood cells (see Aspholm et al. 2006).

Light microscopy picture taken by C. Semino-Mora and A. Dubois using a Nikon Eclipse E800 Microscope and a QImaging MicroPublisher 5.0 RTV digital camera. Biopsy provided by V. Simko, Brooklyn VA Medical Center. Original magnification: 400x.
DOI: 10.1371/journal.ppat.0020121.g001

Thursday, May 24, 2007

This Week's Citation Classic

This week's citation classic is Avise, J.C. & Selander, R.K. 1972. Evolutionary genetics of cave-dwelling fishes of the genus Astyanax. Evolution 26: 1-19.

The results of this paper do not revolutionize science or subvert the dominant paradigm or even overturn long cherished dogma. In fact, the results are fairly inconclusive. The main result is that troglobitic (i.e. cave-dwelling) fish exhibit much less genetic diversity than do epigean (i.e. surface-dwelling) fish, but the authors cannot do more than offer speculative hypotheses for why this should be. Nonetheless, I still think this paper is pretty damn cool. John Avise is currently a Distinguished Professor at UC: Irvine, and this was his very first publication consequent his thesis work under Robert Selander at the University of Texas. Not bad for a Master's student.

The main reason why I dig this paper so much was that it was my first exposure to the cave-dwelling fishes. The cave-dwelling fishes are very much like their epigean counterparts, but they lack eyes! I repeat, they are eyeless... they have no eyes. Well obviously, you say, eyes are not required in the stygian blackness of the subterranean world so mutations in eye genes were no longer deleterious and they accumulated more and more mutations until the eyes finally faded away.

Not so fast... it turns out that there is more to the story than first appears, and, in fact, it is a testament to the strength of natural selection. See there's a gene called Hedgehog that is crucial to the development of the eye. If you favored the neutral mutation theory, you'd expect that in Astyanax, Hedgehog is inactive due to accumulating mutations. Not quite. Hedgehog is upregulated in cave-dwelling fish! Much more of the developmental protein is produced in cave fish and in surface fish, and, what's more, this overproduction is responsible for the eye deformities.

Why should this protein be overproduced? The likely answer is that the gene is pleiotropic; Hedgehog also controls the development of the teeth, cranium, and tastebuds among other things. Perhaps upregulation of Hedgehog aided Astyanax foraging, and in surface fish, this benefit was traded-off against the need to have functioning eyes. The loss of eyes does not matter for Astyanax so they are able to take full advantage of Hedgehog upregulation. Natural selection favored eyeless fishes because they were better able to survive and reproduce than eyed fishes. How cool is that?

William Jeffery published a paper on this material in Journal of Heredity. Carl Zimmer and PZ Meyers also wrote about cave fish for their respective blogs: The Loom and Pharyngula.

Photo from the Jeffery Laboratory at UMD, the leading laboratory studying the cave-dwelling fishes.


There's a new Evilutionary Biologist in the blogosphere. We cordially welcome Jonathan Marshall and look forward to his posts at Science, Politics, Religion et al. Dr. Marshall is a faculty member at Southern Utah University and specializes in phylogenetics.

Interestingly, Jon began his blog soon after meeting Carl Zimmer of the Loom (Zimmer gave a couple of invited lectures at SUU this past March). Carl apparently has this effect on evolutionary biologists; after coming into contact with him, they begin blogging. Zimmer posted about this trend earlier this year.

The Origin of Species

Traditionally, evolutionary biologists assumed speciation occurred when a population was split geographically (e.g. a canyon forms dividing a population in two, also known as allopatric speciation). The subdivided populations then undergo differential adaptation and eventually become reproductively isolated. Ta da! New species!

More controversially, species can also form in a non-geographically subdivided population (i.e. sympatric speciation. Huber et al. report on a possible example of sympatric speciation in progress in the archetypal symbol of evolution: Darwin's finches.

Here a population of the medium ground finch, Geospiza fortis, features large and small
beak morphs with relatively few intermediates.On the right is the large beaked morph, and on the left is the small beaked morph of the medium ground finch. In one of the best characterized examples of evolution in action Peter and Rosemary Grant showed that the Galapagos finches probably diverged due to diverged to variation in local food availability and inter- or intraspecific competition. Presumably these factors are also driving the differentiation of these finches.

However, the most important part of Huber et al.'s part is there microsatellite DNA analyses showing that the large and small beak morphs represent two partially distinct gene pools caused by assortive mating. That is, small beaked females prefer to mate with small beaked males and vice versa. One factor driving these preferences might be selection against birds with intermediate sized beaks, which have been shown to suffer increased mortality relative to the other morphs. Come back in a few years, perhaps by then these two morphs will be reproductively isolated, and officially, different species.

Top Image: Species of Darwin's finch, from a colour plate by John Gould in Zoology of the Voyage of H.M.S. Beagle (1839–43), based on specimens collected by Charles Darwin on the Galapagos Islands.

Tuesday, May 22, 2007

Become a Friend of Charles Darwin...

1,004 members and counting. It's free and allows you to put the letters FCD after your name. While that might not be as prestigious as FRS, it says a lot in certain circles.

It was stranger than any imagination could have conceived...

Today's Science Times has a great article and some amazing photos of deep sea creatures. Such bizarre, beautiful diversity down there! Depicted above is a Ping Pong tree sponge. I am speechless.

The images come from a new book by French journalist and film director Claire Nouvian, “The Deep: The Extraordinary Creatures of the Abyss” (University of Chicago Press, 2007) .

Monday, May 21, 2007

How to Write Consistently Boring Scientific Literature

I remember writing lab reports as an undergrad. We were instructed to write in passive voice, use jargon and remove all traces of humanity from our writing. My nascent attempts at levity and personality were stabbed at with red ink pens. The idea that scientific literature must be boring, passive and devoid of all personal touches is thoroughly ingrained in the scientific hive-mind. Why is it then that many of our favorite papers are often the most poetic? Darwin's On the Origin of Species is absolutely a masterpiece of literature. WD Hamilton consistently wrote humorous, imaginative papers. Richard Feynman's Six Easy Pieces doesn't hide his startlingly lucid, agile, and contagious enthusiasm. The lepidopterist Vladimir Nabokov also wrote several successful fiction novels, including Lolita.

So why are many scientific papers such a bore to read? Kaj Sand-Jensen has some suggestions on How to Write Consistently Boring Scientific Literature.

1. Avoid focus
2. Avoid originality and personality
3. Write l o n g contributions
4. Remove implications and speculation
5. Leave out illustrations
6. Omit necessary steps of reasoning
7. Use abbreviations and jargon
8. Suppress humor
9. Degrade everything to statistical elements
10. Provide citations for self-evident statements

If you want to write good papers, do the opposite. Also, I might add, come up with a good title. Here are some examples of my favorites...

Geometry for the Selfish Herd
(WD Hamilton 1971)

The Spandrels of San Marco and the Panglossian Paradigm
(Gould and Lewontin 1979)

Homage to Santa Rosalia (Or Why Are There So Many Kinds of Animals?)
(GE Hutchinson 1959)

The Paradox of the Plankton
(GE Hutchinson 1961)

The Logic of Animal Conflict
(Maynard Smith and Price 1973)

Would Bohr be Born if Bohm Were Born Before Born?
(H Nikolic 2007)

One Ring to Rule Them All and in the Darkness Bind Them?
(Bena and Warner 2005)

Wise, Winsome or Weird? Mechanisms of Sperm Storage in Female Animals
(Neubaum and Wolfner 1999)

Can a Biologist Fix a Radio? or, What I Learned while Studying Apoptosis
(Lazebnik 2002)

Ecological Traps

We often assume that animals always behave in their own best interests, but this is patently not true. Because their access to and ability to assess information is limited, animals make choices based on their evolutionary history. If, in the past, obeying a certain environmental cue lead to fitness-increasing benefits, then organisms that followed that cue would have more descendants than those that did not.

However, environmental cues are not always consistent or reliable. Animals may obey an environmental cue even if it presently has negative consequences because they are unable to tell the difference. Unfavorable habitats that present cues associated with favorable habitats are termed ecological traps. I suspect a good example of an ecological trap might be found in El Salvador. According to an article by Alberto Barrera, "An artificial lake in El Salvador brimming with sewage and industrial waste is mystifying scientists by attracting thousands of migratory and sea birds."

"Environment ministry ornithologist Ricardo Ibarra said birds may be attracted by the sandy beaches, crawling with insects, that appear around the edge of the lake in the dry season."

Presumably beaches crawling with insects might have cued good habitats in the past, but, in this case, may be associated with high levels of chromium and lead.

"The contamination is bound to be harming birds that feed and nest there, possibly making them too weak to be sure of making their migratory flights or affecting the strength of the shells of their eggs, he warned."

Another example of an ecological trap is the mayfly. Ordinarily mayflies lay their eggs on pond surfaces, but lately have been laying their eggs en masse on road surfaces. Scientists have shown that mayflies the polarized light reflected from roads closely mimics that from pond surfaces. Unable to tell the difference, mayflies have been laying their eggs on roads with obvious negative consequences.

Photo by Impactmedia.

Saturday, May 19, 2007

Science blogging...

There has been quite a dust-up over the Liu and Ochman PNAS manuscript on flagellum (which I wrote about here). The paper has engendered vigorous debate, some of it quite personal. Naturally one hopes that civility of discourse could be maintained, but it's the internet, the medium that gave us the need for the term, flame war. It's good that there is a debate around the Liu and Ochman paper; that's how science progresses. For my part, I posted about it because I hoped to spread the word, particularly since it seemed to disabuse an old creationist chestnut (which it may or may not). I'm no expert in the subject matter so I am done with it; let the experts have at it. I've moved on looking for other interesting things...

That, my friends, is the reason why I began blogging, and why I read blogs. Since I started blogging, I feel more in touch with the literature and more in tune with what is happening in science. It has been a strongly positive learning experience. For example, I just read a great post over at This Week in Evolution. Quite thought provoking. I remember reading the title of the paper in question the week it came out and thinking, Interesting, I should read this. I saved the PDF on my hard drive, but I forgot to have another look. Before I began blogging, that paper may have languished in my hard drive for months, if not forever. Not this time. Ford Denison's post has inspired me to read it at once.

Hopefully more scientists will join the blogosphere, and communities of us will form, highlighting important ideas, criticizing others, and generally, synergystically, spreading the best memes far and wide. No longer shall great ideas slowly filter forth from the august pages of obscure journals via academicians in ivory towers. The internet communication provides access and speed, and has brought us over the cusp of a cultural revolution.

Thursday, May 17, 2007

Petitions for Open Access

As a taxpayer, you pay for research via the National Science Foundation and the National Institutes of Health (among others). Why should you (and everyone else) be forced to pay to access the data and the publications resulting from your tax dollars?

Sign the Petition for Public Access to Publicly Funded Research in the United States

Hat tip to Open Reading Frame

Update on SREL

Reconcilation Ecology posted an update on the Savannah River Ecology Lab situation. Seems vaguely promising. I posted details on the situation earlier.

This Week's Citation Classic: What Is Life?

The Origins of the Reductionist Program

"How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?" Erwin Schrodinger - What is Life - 1944

This week's citation classic is a book by Erwin Schrodinger (of the cat fame), What is Life? It is notable, not for its influence on biologists, but rather for its influence on physicists.

Schrodinger was a Nobel Prize-winning physicist, most cited for his work on wave mechanics, who had the temerity to cross disciplinary boundaries and publish a short text intended for the layperson interested in basic biology and physics. Indeed biologists at the time attacked it on account of its naivete and extreme reductionism. The book's overriding contention was that all of biology could be reduced into chemical and physical laws, a statement that most biologist today will agree with. However, back in the day, reductionist beliefs were definitely not in fashion; it was strongly opposed by scientists such as Wigner, Polanyi, Elsasser, and Koestler. There were many holdouts clinging to the edifice of vitalism long after the luminiferous ether and the phlogiston theory faded from scientific relevance.

What is Life? was largely ignored by biologists, but embraced by chemists and physicists. Chargaff, Stent, Benzer, Delbruck, Symonds, Meselson, Watson, Crick, Wilkins, Luria, Appleyard et al. were all lured to cross disciplinary boundaries after reading the text or interacting with those who did.

Schrodinger's book had a very positive effect on me and got me, for the first time, interested in biological problems. ----Maurice Wilkins

On those who came into the subject just after the 1939-1945 war, Schrodinger's little book... seems to have been particularly influential.... Schrodinger's book was very timely and attracted people who might otherwise not have entered biology at all. ----Francis Crick

[After reading WIL], I became polarized towards finding out the secret of the gene. ----James D. Watson

Delbruck first entered my life in the form of a chapter heading ‘Delbruck’s model’ in Schrodinger’s book What is Life? I read that book at an impressionable age, while still a graduate student in solid state physics.----Seymour Benzer

Schrodinger, then, can be credited with inspiring a generation hell-bent on discovering the nature of the gene, and by 1970, they had largely succeeded. The reductionist program has been taken to its logical extent, delving the depths of molecular biology, the nature of the gene and the biochemical basis of life. Today the reunification of organismal and reductionist biology is well underway, and biology is ever stronger for its conceptual foundations in chemistry and physics.

Carnivorous Sponges

Scientists have just begun to assess the ocean's biodiversity. A recent expedition found a treasure trove of 700+ species deep in the Weddell Sea area of the Antarctic Ocean. The official report is in the journal Nature.

"Heart-shaped sea urchins, carnivorous sponges, and giant sea spiders the size of dinner plates are among the surprising discoveries brought up from the seafloor about 2,300 to 19,700 feet (700 to 6,000 meters) beneath the Antarctic waves."

The authors note that, "Our findings challenge suggestions that deep-sea diversity is depressed in the Southern Ocean and provide a basis for exploring the evolutionary significance of the varied biogeographic patterns observed in this remote environment."

Wednesday, May 16, 2007

DNA Data Storage

Some ideas inspire awe, some ideas inspire the comment, "Damn, why didn't I think of that?"

A recent paper in Biotechnology Progress provoked the latter comment from me. Here Yachie et al. 2007 describe a living data storage system. The ability of DNA to encode information is well known; DNA sequences code for amino acid sequences of proteins. Combine that with the ability to construct custom DNA sequences and to clone specified DNA sequences into organisms, you've got a super data storage system.

Yachie et al. write, "Duplicated data encoded by different oligonucleotide sequences was inserted redundantly into multiple loci of the Bacillus subtilis genome. Multiple alignment of the bit data sequences decoded by B. subtilis genome sequences enabled the retrieval of stable and compact data without the need for template DNA, parity checks, or error-correcting algorithms."

Oh that's pretty cool. Say you want to save the information, "Mary had a little lamb." You could have nucleotide base triplets signify the letters of the alphabet, i.e. aaa = A, aac = B, aag = C and so on. Construct a DNA sequence reflecting your code for "Mary had a little lamb." Insert the oligionucleotide sequences redundantly into multiple locations in the non-coding regions of the B. subtilis genome. When you want to read your message at a later time, use primers to amplify the coded regions, then sequence and enjoy! The redundancy ensures that any errors (i.e. mutations) will be detected during multiple alignment software.

Oh and there's more. B. subtilis can be induced to form spores that can survive for millions of years. Compare that to DVDs and CDs. Seriously... cassette tapes were more reliable than CDs. Of course storing info this way is a bit expensive, but when the costs drop, perhaps we will use bacteria or viruses instead of silicon chips!

Photo by Yoshiaki Ohashi.

Tuesday, May 15, 2007

Bacterial Mitosis

A really nice article about Bacterial Mitosis can be found at Small Things Considered. It evaluates a recent paper on how plasmids are partitioned to the daughter cells during division of their host bacterium. I always assumed that plasmids segregated randomly. For this reason, I found it puzzling that low-copy number plasmids existed. Say a dividing bacterial cell has 2 plasmids. If the plasmids are randomly distributed within the cytoplasm, then the occurrence of plasmids in the daughter cells will follow a Poisson Distribution. That is, the pair of daughter cells will have three possible states: 1:1, 0:2 and 2:0 number of plasmids. Obviously that isn't good if the plasmids "aim" to maximize their reproduction. Two of the three cases do not entail any reproduction at all.

But actually bacterial cells appear to undergo a primitive form of mitosis.

"The researchers isolated a three-component system from these cells that acts somewhat like a mitotic spindle when reconstituted in vitro. Those three components are two proteins encoded by the plasmid par operon (ParM and ParR) and a specific centromere-like DNA sequence within the operon (parC)."

This system allows the dividing cell to partition plasmids equally between daughters. How cool is that?

Monday, May 14, 2007

Help Citizendium!

Citizendium is a new Wiki project that aims to avoid the problems Wikipedia faces from vandalism and inaccurate postings. The key innovations are that contributors must use their real names and all posts must be approved by expert editors (I'm an editor in the Biology Workgroup).

However Citizendium needs money to get off the ground. You can help at no cost to you. Citizendium is now participating in programs with both Amazon and Barnes & Noble that allow Citizendium to earn money for any purchases that are made by people clicking through to either site via Citizendium. This means you can help support the Citizendium with your everyday purchases through these retailers--and it won't cost you any extra! Amazon and Barnes & Noble will donate 6% of the purchase price for all book purchases that originate at the Citizendium website.


There's an amusing article by Richard Wiseman over at New Scientist. I take most of the "studies" with a grain of salt, but its fun to read nonetheless. Here are some interesting "facts".

--[O]ne demographical group has come to stand out above all others as being most likely to push boundaries and break rules. These are not disaffected teenagers nor Italian football hooligans. They are women van drivers.

--[People] would rather have worn a sweater that had been dropped in dog faeces and not washed - raising genuine health concerns - than a laundered sweater that had been worn by a mass murderer.

--According to research carried out by Robert Sommer at the University of California, Davis, in 1988, lemons are seen as dislikable, onions are stupid, and mushrooms are social climbers.

How did these studies not win Ignoble Prizes?

Thursday, May 10, 2007

This Week's Citation Classic

Sanger F, Nicklen S, Coulson AR. 1977. DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U S A 74: 5463-7.

This paper describes the most important (IMHO) technical breakthrough in the biological sciences: DNA sequencing using a single-stranded DNA template, a DNA primer, a DNA polymerase, radioactively or fluorescently labeled nucleotides, and modified nucleotides that terminate DNA strand elongation.

Prior methods depended on partial hydrolysis and were painfully slow. It was a big deal when Gilbert and Maxam reported in 1973 the sequence of a whopping 24 basepairs using a method known as wandering-spot analysis. Contrast this to the ~3 billion base pair human genome. Clearly the process needed to be sped up in order to be useful.

The key innovation of the Sanger method was the use of dideoxynucleotides triphosphates (ddNTPs) as DNA chain terminators. The basic idea is that the florescently labeled ddNTPs will stop chain replication wherever they are incorporated into an elongating DNA strand. DNA fragments of various lengths are separated by electrophoresis and the fluorescent tags are "read" give the nucleotide sequence. The whole procedure relatively simple and is adequately described in wikipedia.

Sanger et al.'s technique was used to determine the sequence of the DNA bacteriophage PhiX174 which contains 5,386 nucleotides, the first DNA based organism ever to have its complete genome sequenced. (The first organism was MS2, an RNA bacteriophage).

It is true that the process was eventually sped up using thermally stable (e.g. Taq) DNA polymerases, capillary electrophoresis and dedicated thermal cyclers, but the basic technique is still used today.

Alas today, chain termination sequencing is being replaced by newer quicker methods, especially pyrosequencing. Chain termination methods are probably inadequate to compete for the Genomics X prize given to the first team build a device capable of sequencing 100 human genomes within 10 days or less with an accuracy of no more than 1 error in 100,000 base pairs, with sequences accurately covering at least 98% of the genome, and at a demonstrated cost of no more than $10,000 per genome.

Frederick Sanger was awarded his second Nobel Prize for this work in 1980.

Figure: a typical sequencing four-color chromatogram.

Why is there so much genetic variation?

One of the surprising discoveries when scientists first began looking at genetic variation was that there was a great deal more than expected by theory. In 1966, Richard Lewontin and Jack Hubby published a paper that revolutionized population genetics. They pioneered the use of protein gel electrophoresis to survey dozens of loci in the fruit fly, Drosophila pseudoobscura, and reported that a large fraction of the loci were polymorphic, and that at the average locus there was about a 15% chance that the individual was heterozygous. These results are surprising because it was expected that natural selection will reduce the amount of genetic variation in populations.

Forty years later evolutionary biologists still don't have many solid explanations for genetic variation in nature. However, a recent report in Nature by Fitzpatrick et al. shows that negative frequency dependent selection can maintain alternative feeding alleles in populations of fruit flies. Fruit fly larvae forage for food in two ways: by "roving" or "sitting". Rover larvae move around more than sitter larvae while feeding and they are also more likely to explore new food patches than sitters.

Fitzpatrick et al. discovered that each type was favored by natural selection when rare.

"If you're a rover surrounded by many sitters, then the sitters are going to use up that patch and you're going to do better by moving out into a new patch," says Marla Sokolowski, the PI on the research team. "So you'll have an advantage because you're not competing with the sitters who stay close to the initial resource. On the other hand, if you're a sitter and you're mostly with rovers, the rovers are going to move out and you'll be left on the patch to feed without competition."

Similar behaviors occur in C. elegans, which tend to clump or browse bacteria solitarily. I unsuccessfully looked for frequency and density dependent selection among these worms, but it is likely my assays weren't sensitive enough. The foraging gene is found in many animals, including honeybees, mice and humans. It is interesting to speculate on the roles that it plays in higher organisms, such as ourselves. Does it play any role in food-related behavioral disorders?

Wednesday, May 9, 2007

Marsupial Genome Sequenced

A report in Nature has announced that the first marsupial genome has been sequenced. Tarjei Mikkelsen of the Broad Institute in Cambridge, Mass and team sequenced the 3,475 megabase genome of the South American grey short-tailed opossum, Monodelphis domestica. The opossum genome appears to contain about 20,000 protein-coding genes, the authors found, and the vast majority of these are also found in placental mammals. Apparently most of the differences between marsupial and placental mammals comes from junk... ahem... non-coding sequences, not proteins. It provides more evidence the main difference between you and other animals is how your genes are regulated not the proteins you possess.

Oh and that isn't the only time I've seen 'possums in the news lately.

Apparently a homeless person seeking shelter from the rain in a trash bin was accidentally dumped into a garbage truck. Trapped in the garbage compactor, the man was able to avoid being crushed by grabbing a...

a) a steel pole
b) a brace
c) our marsupial cousin, Didelphis virginiana

If you picked, c, the Common Opossum, you get a medal.

Our friend Marko from Croatia writes "Are opossums that common?"
Yes, Marko, Common Opossums are in the International Union for the Conservation of Nature and Natural Resources' category of Least Concern.

Monday, May 7, 2007

Question of the Year

What would you do if you could sequence a genome for $1,000? In celebration of its upcoming 15th anniversary, Nature Genetics is asking prominent geneticists to weigh in on this question: what would you do if this sequencing capacity were available immediately? The responses are interesting.

Bruce Lahn would sequence "the genomes of a large number of cells from a single individual... to construct an ontogenetic tree of all the cells based on somatic point mutations."

Paul Nurse would sequence "a selected set of genes for as many species as possible... [and] bury the creationists and the intelligent designers under a mountain of base pairs."

Laurence Hurst would "love to know what underpins the heritable differences in musical ability."

Elaine Ostrander
wonders "what are the genetic mechanisms that control the breed-specific behaviors of various domestic dog breeds?"

Francis Collins would determine where the soul is located. Wait, no, just kidding. He would use "genomic research to improve human health...for each of 30 common, complex diseases, such as asthma, arthritis, diabetes, various types of cancer, heart disease, stroke, Alzheimer's disease and depression."

What would you do?

Sunday, May 6, 2007

Genes in Conflict

"The conflict between maternal and fetus genes is one of the weirdest ideas in the modern theory of evolution."* According to evolutionary logic, the fetus "wants" to milk the mother for all it can get; the mother "wants" to restrict the fetus to what it needs to survive and save something for future offspring. The reason is that the fetus benefits from every bit of help the mother gives, while the mother's return on her investment diminishes with increasing investment, (i.e. ever greater investment won't necessarily increase her fitness).

One example of this struggle is the regulation of the mother's blood sugar, which is much than normal higher during pregnancy. Well this makes sense, you might think, because the mother is now feeding a growing fetus. But look at the mother's insulin level, it also is much higher than normal, and insulin is used to down-regulate blood sugar levels. Huh, that's weird, she is secreting more insulin, yet her blood sugar level is ever higher. She must be responding less to insulin. Why should that be?

David Haig suggested that the fetus is trying to increase blood sugar levels by releasing human placental lactogen (hPL, a hormone that reduces the effects of insulin) into the mother's bloodstream and the mother is trying to reduce blood sugar levels by increasing more insulin. The amount of hPL in the mother's blood is astonishing, on the order of 1000-2000x the level of comparable hormones, and the amazing thing is that hPL is entirely unnecessary because babies with nonfunctional hPL genes are completely normal at birth. So the mother and fetus are battling over the allocation of resources by pumping out more and more hormones.

But wait that's not the weird part! The weird part is, strictly speaking, the conflict is not between mother and fetus, but rather between genes within the same individual. The fetus that contains a gene causing it to release more hPL will someday, provided it is a female, grow up to be a mother whose offspring may contain that very same gene and will be trying to suck every bit of nourishment out of her. The gene is then, within the very same individual, advantageous during fetus-hood and disadvantageous during mother-hood. The net result is that the fetus loses out by possessing the hPL gene, its lifetime reproductive output is reduced, but it doesn't matter. The gene spreads anyway because the gene increases its representation in the gene pool.

There is then an inherent inefficiency in life. The intragenomic conflict leads to reduced reproductive output, through less efficient use of resources and, more importantly, in the hPL case, through increases in the onset of diabetes. 10% of pregnancies result in gestational diabetes; and 50% of the cases of gestational diabetes results in full diabetes later on in life. Would that be object of an intelligent designer?

Photo by Street Cow.
*Ridley, M. 2001. The Cooperative Gene. The Free Press.

Saturday, May 5, 2007

Unidentified Biological Organism

A diver named Jay Garbose videotaped this "creature" off the coast of Juno Beach, Florida. The creature has been tentatively identified by the Smithsonian as an unknown species of Nemertean Worm. They said he could name it if he found it again... ha ha. Nonetheless it looks pretty freaking cool. I'm amazed that anything of that size could have escaped notice for so long, especially off the busy coast of Florida.

Garbose says, "At first I thought it was a sea cucumber although no one's ever seen one stretched 7 to 10 feet the way this one was. It's sort of grey and putty-like and very smooth and taffy-like in the way it stretches. Some of my friends and I have sort of dubbed it the living intestine."

There's a video here.

Thursday, May 3, 2007

I am Convinced that It is the Light and the Way

This comment on natural selection is the last sentence of Adaptation and Natural Selection, George Williams' masterpiece about evolution. An evolutionary biologist I know (who shall remain anonymous to spare him/her public shaming) claimed not to know who was George Williams. I was/still am aghast. This anonymous evolutionary biologist is the inspiration for this post, indeed for this series of citation classics. Williams is a professor emeritus at SUNY: Stony Brook, author of numerous influential books, and recipient of the 1999 Crawfoord Prize. In the words of no less a luminary than Stephen Pinker, "George Williams was instrumental in making natural selection an intellectually rigorous theory".

Today's citation classic is Williams, G.C. 1957. Pleiotropy, natural selection, and the evolution of senescence. Evolution, 11: 398-411. It was Williams' first significant paper and considered by many to be a cornerstone of modern evolutionary theory. At the time, aging was a major problem in biology (actually, it still is). In 1956, Alex Comfort wrote in The Biology of Senescence*, "In almost any other biological field, it is possible to ... show a steady progression from a large number of speculative, to one or two highly probable, main hypotheses. In the case of senescence this cannot profitably be done."

At the time of publication of Williams' Evolution of Senescence, many biologists considered aging an evolutionary adaptation. In an article in Science, Carl Zimmer (The Loom) wrote, "Williams recalls a lecture he heard by Alfred Emerson, a zoologist at the University of Chicago, about why people age and die. 'He said growing old and dying is a good thing,' Williams says. 'We’ve evolved to do it so we get out of the way, so the young people can go on maintaining the species. I thought it was absolute nonsense,' says Williams."

Williams' Evolution of Senescence paper was his opening salvo in his war against this "nonsense", this fuzzy-headed, group selectionist thinking. Views such as those held by Emerson were common. They culminated in V.C. Wynne-Edwards' book, Animal Dispersion in Relation to Social Behavior, where it was argued, for example, that many animals formed groups so that they could assess population density, and regulate their own numbers to avoid overpopulation. Balderdash! Humans, even with all our intellectual gifts, can't regulate our own population. Most adaptations benefit the individual, or more correctly, the gene producing the trait, not the group or any other higher level of biological organization. W.D. Hamilton later wrote "Geometry for the selfish herd" (a classic in its own right) to show that animals often grouped to reduce their own risks of being preyed upon.

In "Pleiotropy, natural selection, and the evolution of senescence", Williams argued that senescence was not an adaptation to remove old-folks to make room for young'uns. Rather senescence was the result of an evolutionary trade-off. Selection favored genes that enhanced reproduction in youth even though they were deleterious in old age. In Williams' words,

"So natural selection will frequently maximize vigor in youth at the expense of vigor later on and thereby produce a declining vigor (senescence) during adult life.... The rate of senescence shown by any species will reflect the balance between this direct, adverse selection of senescence as an unfavorable character, and indirect, favorable selection through age-related bias in the selection of pleiotropic genes."

In other words, genes for vigor late, as opposed to early, in life aren't favored because one's reproductive probability is at its maximum at reproductive maturity and subsequently declines as the cumulative probability of death increases. Less formally, better hurry up and reproduce, kid, before you get hit by a bus or something.

There is no biological law that says the body must wear out, that we must age, that we must die. Hypothetically, it should be easy enough to live forever as the energy expenditure for maintaining the present structure pales in comparison to the expenditure required to make a new body from scratch. What we observe as senescence, then, is just the consequence of genes selected for the reproductive advantages they provide during youth. As Zimmer writes, "Ironically, cancer, declining stamina, deteriorating vision and various diseases of old age could all be the result of natural selection". The possible genes producing these phenotypes simply have to make you more fecund at reproductive maturity.

Frans Roes interviews Williams here and touches on the above themes.

Williams recounts some of his adventures here at the Edge.

*During the George Williams symposium at SUNY: Stony Brook, I happened, as is my wont, to visit a local bookstore, and was delighted to find a 1st Edition copy of Comfort's The Biology of Senescence with Williams' stamp inside and annotated by Williams himself.

Take Action to Save the Savannah River Ecology Laboratory

The DOE is shutting down the Savannah River Ecology Laboratory. I suspect the current anti-science administration in Washington is behind the decision. Here's what you can do to help: SREL Action letter.

Other Blogs on this Issue

1. The Austringer: War On Science Continues: Savannah River Ecology Laboratory on Chopping Block
2. Thoughts From Kansas: Save the SREL
3. blustrydaz: This is really not good! (my graduate research is here!) If you get the chance, pls write a letter!
4. evolgen: DOE to Cut Funding to Major Environmental Research Laboratory
5. De Rerum Natura: Savannah River Ecology Laboratory in Jeopardy.

Wednesday, May 2, 2007

Peer Review Revisited

Madhusudan Katti over at Reconciliation Ecology picked up the thread about the issue of slow peer review. He makes some interesting comments, particularly regarding the time constraints at teaching-orientated institutions. I've thought a bit more about the issue and have a few more points to make regarding possible solutions.

What are the alternatives?

1. Do nothing.
-Is there really a problem? One could argue that time-to-publication times are faster now than ever, particularly with internet submissions. Being relatively new to the science publication business, I don't have any insight into what it was like back in the day. Perhaps some old-timers senior researchers could chime in on this.

2. Financial incentives
-Some have suggested paying reviewers. I think this is a non-starter. Most scientific societies are already strapped for cash. Besides it just introduces a whole new layer of potential conflicts of interest. Besides aren't we all getting paid already by our institutional salaries?

3. Service Counts
-Madhu suggests increasing the impact of service (and peer review) in the tenure review process. Great idea. However, someone (a tenured faculty who had served on many review committees) once said that tenure counts for ~10% of the decision. Someone else said that service counts for nothing! Whatever the impact of service, it is part of an institution's culture, and institutions are notoriously slow to change.

4. Penalties
-The original PLoS article suggested time penalties for late reviews. This is probably unworkable as well. Slow does not equate poor quality. James Crow wrote a Perspective in Genetics about peer review.

"Sewall Wright was a particularly thorough reviewer. When he received a manuscript for review, he typically dropped other activities and went over the copy in great detail. Usually this involved his redoing all the calculations and reanalyzing the data. Alex and I were convinced that he was spending too much time on other people's data, at the price of not getting his own more important work done. For that reason, we employed him sparingly, only where his unique insights were essential.

A review that stands out in my mind involved a study of quantitative traits in rodents. As usual, Wright reanalyzed all the data. He suggested a large number of changes, the most significant of which was to suggest a scale transformation of the data, which not only greatly simplified the interpretation, but also led to the opposite conclusion. The author made almost all of the suggested alterations and obligingly reversed the conclusion."

I suppose by Hauser and Fehr's standards, Wright's papers would never be published.

5. An interesting suggestion by Gavin Sherlock of Stanford is to match reviewers.

"An alternative system, which doesn't require holding articles in editorial limbo (which seems not to be in the editorial spirit) is to choose the reviewers of the article based on the length of time those reviewers typically take, and the length of time that the author usually takes, matching them up. Thus, if you usually take 6 weeks on average to review a manuscript, your manuscripts will be sent to reviewers that usually take that long too. On the other hand, if you normally review within a few days, you manuscripts will be matched up with suitably rapid reviewers."

This is an interesting option that deserves consideration, but it might turn out unworkable in the long run as it requires extensive databases on reviewer habits.

6. Greater Editorial Action
-Perhaps editors could be more responsible for review timing. I don't think this really has merit. Editors are thinly stretched as is, and chasing reviewers is one of the worst aspects of the job.

7. Open Access Reviews
-Nature attempted an experiment in Open Peer Review. While it was not an unqualified success, perhaps it takes time to change the inertia of the peer review culture. Of all the ideas I've heard, I think this one probably has the most merit. It would increase the democratization of science as well as make the review process a bit more transparent.

Can a Penn State center predict and prevent the next pandemic?

One of the hottest new research centers in the US is the Center for Infectious Disease Dynamics at Penn State. This month's The Scientist contains an article on the new center, highlighting the fact that the center has been particularly successful at attracting new faculty.

"Daniel Falush, an evolutionary geneticist at Oxford University, describes one effect CIDD has had in the United Kingdom: 'There was a great sucking sound because these famous British scientists were disappearing to Penn State.'"

CIDD's mission is to investigate infectious diseases both from theoretical and applied standpoints.

"Investigation of key biological questions Our research addresses issues of fundamental importance in biology. For instance:

  • Many disease agents have a sufficiently short generation time that ecological and evolutionary dynamics operate on similar timescales. Consequently, host-parasite relationships provide a tractable system for investigating key questions in population and evolutionary biology.
  • Though their interactions with host immunity are complex, some disease agents have small enough genomes that we can begin to dissect the molecular basis of important large-scale phenomena such as species barriers to transmission and herd immunity.

By collaborating across different disciplines, CIDD researchers cast important biological problems and processes in useful new lights. Application to disease management and control Infectious diseases have an immense impact on human health, agriculture and conservation. CIDD research has considerable relevance to management and control of pressing disease issues such as disease emergence, bio- and agro-terrorism and epidemic control strategies."

I've got a personal connection to CIDD. One of my former labmates, Siobain Duffy, is now a postdoctoral researcher in Eddie Holmes' Lab. Duffy is an amazing scientist and I can't wait to see what she discovers in her new position.

The photo, courtesy of the National Institute of Allergy and Infectious Diseases, shows HIV daughter viruses being shed from a T-cell.

Tuesday, May 1, 2007

Support Open Access

"Shortly after a large-scale clinical trial in 1955, the first inactivated polio vaccine was being injected into tens of millions of people around the world - possibly the most successful pharmaceutical product launch in history. Asked why he had not obtained a patent on the phenomenally successful vaccine, Jonas Salk reportedly replied, "That would be like patenting the sun." A few decades later, this view seemed laughably quaint." Alan Dove, When science rides the MTA, J. Clin Invest. 110:425-427 (2002)

Science Commons: Science Commons serves the advancement of science by removing unnecessary legal and technical barriers to scientific collaboration and innovation.

Built on the promise of Open Access to scholarly literature and data, Science Commons identifies and eases key barriers to the movement of information, tools and data through the scientific research cycle.

Our long term vision is to provide more than just useful contracts. We will combine our publishing, data, and licensing approaches to develop solutions for a truly integrated and streamlined research process.

See also: Scientific Commons: aims to provide the most comprehensive and freely available access to scientific knowledge on the internet.

The Great Science Publication Scam

I'm a big fan of open access publication. However, I haven't quite seen the point driven home like a recent opinion piece in the Harvard Crimson. Thanks to Jonathan Eisen at Tree of Life for pointing it out.

A passage from the article:

"Our professors do the research. They write the papers and proofread them. They even do the peer review. Then they sign the copyright over to publishers, who don’t pay them a dime—they’re paid by grants and salary, our taxes, and tuition. Harvard then pays again for the journals—many of them over $10,000 each—and most of us feel personally the bite each term when we buy our sourcebooks. Many of these cost upwards of $100 not because they’re on paper rather than online (printing costs pennies a page), but because of the fees charged by publishers like Elsevier (1,387 journals ranging across academia) and Wiley (348 journals), some higher than $1 per page. That’s three ways we pay for the same research, writing, proofreading, and peer review. Even Harvard has found the cost too high, and has cut down on its subscriptions."