Tag Archives: nature

BLyS Sequence Analysis

I’ve been playing with some sequence analysis and phylogentic tree construction programs recently because I would like to introduce these sorts of data analysis into my biology classes. As a sample protein, I decided to use BLyS / BAFF, a protein important in regulating B Cell numbers. I’ve always wondered about the origin of this kind of molecule, since working on it in grad school, and this seemed like a decent way to get some ideas about where it might come from.

The first thing I did was go to the NIH’s National Library of Medicine website:

It’s easy to search for any protein / gene / whole genome you are interested in examining. Knowing that BLyS is vital in humans and mice, I chose to start with the human sequence. I retrieved it as the following:

>gi|20196464|dbj|BAB90856.1| BLyS [Homo sapiens]

The easiest tool to find similar proteins in other animals is the Basic Local Alignment Search Tool for proteins, or BLASTp. Just using default settings, I pasted the sequence in the search field and hit go. (note, I actually just used the accession number, not the whole sequence)


This retrieved tons of proteins with similar sequences from the vast database of sequence information, from which I chose several model species. One thing I wanted to do was to include several primates as a sort of internal calibration (assuming that they would all have very similar sequences compared to more distantly related species). I also wanted to get a few animals’ sequences who are quite distantly related to humans (frog and ground tit fir that bill)

Once I had a list, I put them all into a single text file and then used that in a second program. This time, I decided that the best ‘multiple alignment tool’ would be CLUSTALX. It’s been around for a while and can create data in a number of different forms. Besides, it’s free and versions are available for both mac and PC.

Again, for starters, I just accepted the default parameters and did a quick alignment:


Obviously, there’s something odd about the canid familiars (dog) sequence, but before I did anything about that, I just wanted to see what a phylogenetic tree looked like. This is another thing that Clustal does well, it will export your sequence alignment as tree data in a number of formats, then I could plug that data into one final program. This last is a web based program that I access through a french site (but you can probably find it in a number of places). The program is called DRAWGRAM. It accepts alignment data and outputs a graphical tree representation of the alignment.

This is an important logical step… What I’m doing is asking for a family tree of sorts to be displayed that represents the relationship of the sequences I provided. We might want to assume that this also tells us how related the organisms that have these proteins are – and that’s not wrong, but it’s also not thorough as we’re only using ONE protein to make that assumption.

Here’s my first tree:


Note how isolated Canis is on this representation.

Finally, I went back and truncated the Canis sequence to a place where I suspect the protein actually starts – my sequence from the NCBI gave me a string of Amino Acids at the front of the protein that I think are probably not there, but just got added by some computer algorithm without proper human oversight.

Once I did that Canis (by the way, I remained the sequence ‘DOG’ so I was sure it was the new one) fell in line with a sequence more similar to that seen in cats (felis):

ImageThat’s it for now. Although I expect that I will dig a little deeper with more animals to see if I can come closer to an ‘original BLyS’.


  1. Dereeper A., Audic S., Claverie J.M., Blanc G. BLAST-EXPLORER helps you building datasets for phylogenetic analysis. BMC Evol Biol. 2010 Jan 12;10:8. (PubMed)
  2. Dereeper A.*, Guignon V.*, Blanc G., Audic S., Buffet S., Chevenet F., Dufayard J.F., Guindon S., Lefort V., Lescot M., Claverie J.M., Gascuel O. robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W465-9. Epub 2008 Apr 19. (PubMed) *: joint first authors
  3. Felsenstein J. PHYLIP – Phylogeny Inference Package (Version 3.2). 1989, Cladistics 5: 164-166
  4. Larkin,M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J., Higgins, D.G. (2007) Clustal W and Clustal X version 2.0. Bioinformatics, 23:2947-2948.
  5. Thompson,J.D., Gibson,T.J., Plewniak,F., Jeanmougin,F. and Higgins,D.G. (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Research, 25:4876-4882.
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Posted by on March 7, 2014 in Uncategorized


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Evolution Animated

I just stumbled upon this cartoon for the first time today and I’m totally blown away. Sure, there are some things that could be explained better. There are a couple of moments when the illustrations could be a bit more accurate. But, overall, it’s a very good summary of the basic elements of evolution and pretty funny. (I wish I had made this!)

Have a watch and enjoy.

also, check out Kurzgesagt’s other animations on the Big Bang Theory, et al.

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Posted by on March 6, 2014 in Uncategorized


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Photosynthesis: Turning CO2 into O2 – or maybe not.


It’s so simple, right?

“The evolution of photosynthesis remade the Archaean Earth. Before photosynthesis, the air and oceans were anoxic. Now the air is a biological construction, a fifth of which is free molecular oxygen”  – Bendall et al. 2008cIt’s easy to mistakenly think that photosynthesis turns CO2 into O2, people have been doing it for years. In fact, you’d even be remiss not to initially think that it’s the case – it is, after all, a simple conclusion to make and William of Ockham tells us to always start with the simplest ideas.

How could we do this experiment now?

We could  use radiolabeled Oxygen in our CO2 and then look for that same radioactive O2 being produced as a waste from the plant. But if that experiment were done, we’d quickly see that this wasn’t the case. As we will see below, this experiment was eventually what was done and instead of labeled CO2 being produced, the leaves of the plant becoming radio labeled, while only ‘cold’ CO2 was being released. Vexing!

One complication in addressing this idea comes from the very notion of air as being something to begin with. So, what is air? – and what happens (to air) during photosynthesis?

The Dutch scientist and physician, Jan Baptista van Helmont (1579-1644), did some early experiments to understand the nature of photosynthesis. His experiment was to determine where the mass of the plant came from. He suspected that it would be from the soil it was growing in, and did a very simple experiment that refuted this hypothesis. He reasoned that if the mass of the plant came from the soil, then it was a simple conversion that he could observe happening over time as soil was depleted resulting in an equal growth in mass of the plant. His experiment used a potted willow tree planted in 200 lbs of soil. In five years, his 5 lb sprig grew to 169 lbs, using only 2 oz. of soil.

Clearly the mass was coming from somewhere else. Knowing that he watered his tree regularly, he speculated that this was the source of the tree’s growing mass.

Helmont’s experiment did nothing to answer the question directly, but it does introduce a new player into the mix: Water… H2O. There’s Oxygen in water too – another possibility?


What could possibly have killed this mouse?

In 1771 Joseph Priestley came onto the scene with experiments examining the nature of air as something more than just “nothing.” He noticed that a flame tainted the air with a kind of pollutant that was not amenable to animal life. He called this pollutant, phlogiston. Phlogiston could be produced by burning a candle in a closed container until the candle put itself out. Then, any animal (he used a mouse), that was put in this phlogistated air would quickly die. Yet a sprig of mint could counter this effect and somehow clean up the phlogistated air.

What do we know now?

1. Air is not just ‘nothing.’

2. Air quality (composition) is affected by certain biologic and abiologic processes.

a. Candle flames pollute the air with something toxic to animals (at least mice)

b. A mint sprig is sufficient to neutralize or eliminate this pollutant

Another Dutchman, Ingenhousz determined that de-phlogistation by plants occurs only in the light and required he green parts of plants to accomplish this.

(Much of the above material can be found in the excellent History of Research Page)

How to observe these gasses more easily? Perhaps under water, where gas will appear as bubbles.


A simple experimental setup to measure photosynthesis

“When a sprig [of Elodea] is placed upside down in a dilute solution of NaHCO3 (which serves as a source of CO2) and illuminated with a flood lamp, oxygen bubbles are soon given off from the cut portion of the stem. ” -from a History of Photosynthesis. Using this device (pictured below) as a readout, F.F. Blackman measured gas production under various conditions by observing the production of bubbles under a number of conditions.

Data from such an experiment looks like this:


The data

From these data, Blackman concluded that photosynthesis occurred in several stages, the first was a ‘light-limited’ stage that hastened with increasing light intensity, the second did not increase with increasing light intensity and required the work of enzymes (accounting for the effect of heat speeding up the reaction).

The Dutch scientist, van Niel  first suggested the idea of Oxygen gas coming from H2O based on his observations of purple sulfur bacteria converting H2S to S2 and assuming a parallel reaction was occurring in green plants.

CO2 + 2H2S → (CH2O) + H2O + 2S             (observed in purple sulfur bacteria)

CO2 + 2H2O → (CH2O) + H2O + O2             (predicted in green plants)

The final proof of this did not come until Ruben and Kamen were able to use an isotope of Oxygen to trace its route through photosynthesis.

Using algae, given ‘heavy’ oxygen in the form of either water or carbon dioxide, it was found that the isotope given in H2O was invariably that found in the resulting O2. Their experimental procedure is outlined in the diagram as two parallel experiments:



H2O CO2 O2
START 0.85 0.20
FINISH 0.85 0.61* 0.86
START 0.20 0.68
FINISH 0.20 0.57 0.20

So, what we should be saying is not that plants turn carbon dioxide into oxygen, but that plants turn carbon dioxide into sugar, which is precisely why van Helmont was confused by a 169 lb. tree growing from only 2 oz. of soil. He probably never would have believed that all that tree was actually built out of thin air.

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Posted by on September 28, 2013 in Uncategorized


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Magic Bullets


from SAFC global

I just saw that the most recent issue of Science is highlighting a favorite topic of mine, antibody-mediated therapy and B cell biology. I’ve done work in both of these (related) fields in the past and remain an advocate of antibody-tageting of therapies using drug conjugates (e.g. trastuzumab–DM1) or initiating cell-specific effects simply by binding (e.g. anti-CD20). 

In the early 20th century, Paul Ehrlich coined the phrase “magische Kugel,” to describe antibodies as ‘magical’ proteins which could unerringly home in on targets to do a variety of things. Today, we can paint tumors with antibody conjugated with fluorescent dyes, deliver toxic chemicals to cells we wish to eliminate or simply activate / deactivate cells through targeting of receptor proteins.

I’m eager to get my hands on this issue and see what’s new (if anything) in the field and what products are currently in the pipeline of various biotech companies. 


(I’m suddenly struck anew with the misery of not having access to Nature and other journals I’ve always had handy. I’m so glad I at least still have Science! )


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Posted by on September 15, 2013 in Uncategorized


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Coding Challenge

Recently, there have been a couple new revelations about number theory published in Science Within the article was a pair of theories about prime numbers that I had never heard before, one of which was:

Goldbach’s conjecture, [which] makes two assertions: that every even number greater than 2 is the sum of two primes, and that every odd number greater than 5 is the sum of three primes.

I thought it would be fun to start with the first part of this problem and write a program to accept user input in the form of an even integer > 2  and then look for the two primes whose sum is equal to the user provided:

Goldbach_partitions_of_the_even_integers_from_4_to_28_300pxprime1 + prime2 = user input

where prime1 and prime2 may be any prime number (even the same number twice)

I could easily see this escaping the processing power of my machine if the numbers get high, but I think it shouldn’t be too hard to at least write a code that could look for them and demonstrate whether this worked with known input.

Are you up for a quick challenge?

zombie locker

Learn Fractions with Zombies

If so, submit your documented answer here as a comment. Feel free to use any language you would like (I just did it in C++, but I’m eager to see better answers than my own). My favorite submissions will win a free copy of  my iBook, In Parts, Tales of Fractional Zombies, which you can enjoy yourself or regift to a youngster in your life who wants a fun way to learn the concept of fractions.

You can use these links as resources to help check your work:

prime numbers       prime checker

If you are new to coding and are looking for a coding environment to work in, check out this posting for help setting up a C++ coding environment using Xcode (on your mac)


Posted by on June 19, 2013 in Codecademy, Coding


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Release of ‘The Curse of Sisyphus’


The Curse of Sisyphus

The Curse of Sisyphus has been released and is available on the iTunes iBookstore. To celebrate the release, this, and its companion volume, The Thirteenth Labor of Heracles are both free until Sunday.

Zeus is not one to be trifled with. And Sisyphus has been a thorn in his side, defying him at every turn, yet escaping every punishment with uncanny cunning. But this time, the mortal has gone too far and Zeus has a special punishment befitting Sisyphus’ persistence.

The Curse of Sisyphus is the tale unlike others you may have heard about him before. Here you can find out exactly how Sisyphus defied Zeus yet again – and learn about the physics of motion, gravitation and orbit at the same time.

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Posted by on June 13, 2013 in Uncategorized


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Almost forgot


Mercury, the closest planet to the sun has temperatures ranging from 400 degrees C on the surface to -170 degrees C in some permanently shadowed craters.

I was just about to go to sleep when I remembered that my biology class is having a quiz tomorrow and I should post a hint to an extra credit question. Rather than post it here, I’ll refer you to the site that has extraordinary new data about a newly identified water reservoir in our solar system.

Follow this link to Nature’s news story about the finding.

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Posted by on December 4, 2012 in Uncategorized


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