09 July 2010

Love me with my mutation




You need to look beyond genes (genotype) to understand human behavior (phenotype). Today, evolution is not only trying to answer how nature and organisms form and develop; but also it considers development and change of human behavior in hundreds of thousands of years. The original version of the article presented below was published in a Turkish magazine, named NTV Bilim, in March 2009. Thanks to Istem Fer, who translated the document into English, giving me a good reason to share it with the beloved followers of CounterMinds! Enjoy!



In Rocky IV (1985), before the final match between Rocky and his opponent Ivan Drago begins, Drago’s manager quotes: “It is the size that matters. Doesn’t evolution say so? Drago is the best-trained boxer you have ever seen. There is not adequate muscle, strength and genes in that man [Rocky] to win. It is physically impossible for that little man to win!”

However, the end is known; our aggressive hero Rocky whose genes are “so called” incapable, knocks genetic wonder Drago out in the ring just by training in the wild!

It might have not occurred to you that Rocky had delivered the world of genetics a hard blow when he knocked out his gigantic opponent who had far stronger genes than he does. But as a scientist who is interested in evolution, when I saw this scene what came to my mind was that Rocky did not only win a victory over USA’s eternal rival Soviet Russia, but also he slapped scientific world who is trying to find an answer to the question whether genetic or environmental factors are more dominant in the development of individuals.

It is not sufficient to look their genes to understand human behavior. Today, evolution is not only trying to answer how nature and organisms form and develop. Evolutionary biology is a broader field that covers human behavior, development, and changes in hundreds of thousands of years, health and medical science. Such that when evolution tries to find an answer to the “Do genetic factors beat environmental factors?” question that I mentioned above and examine organisms’ behaviors, it wants us to distinguish genetic and environmental factors. So, how do we explain the origin of behaviors such as aggression? Let’s listen aggressive people’s excuses from evolutionary genetics.

The genes mao-a and mao-b (monoamine oxidase) in mammals are just the two of the genes that are responsible from aggressiveness. In our evolutionary history, mao-a and mao-b genes are formed by duplication of a single mao gene in the period of transition from aquatic to terrestrial environment. These two genes are responsible from the production of MAO A and MAO B enzymes. These enzymes react with the hormones that can affect mood like serotonin, dopamine and norepinephrine inside our bodies, especially inside nerve cells. In short, the chemical balance of our mood is inside these two enzymes’ hands. Therefore things change as the balance of these two enzymes’ is spoiled.

Think of it this way: hormone construction and deconstruction continuously goes on in our bodies and these two enzymes are responsible for balancing the hormones. However, as we get older, MAO B enzyme’s activity increases and our cells start to react with more hormone than usual. This changes body’s hormone balance drastically. That’s the reason why we are becoming more aggressive as we get older! If only, the only result of this imbalance was aggressiveness: uncontrolled MAO B could lead to permanent nerve diseases such as Parkinson and Alzheimer.

Another enzyme, in the intersection of evolution and behavior science: MAO A, alone and proud. The gene where to look in order to understand the aggressiveness and anger in males is mao-a. Studies show that, men who have an inherited point mutation in their mao-a gene are aggressive and have a warrior soul. The striking point of the study is this: The men who have a healthy family life in their childhood would not be affected from this mutation in their genes. According to a survey amongst a group of prisoner men, the ones who both have this mutation and an unhappy childhood appear to be more inclined towards violence.

How about women? Mao-a gene is on the X chromosome. Remember that women have two X chromosomes; even there is a mutation in one of them, the other X chromosome can compensate this defect. As it can be seen, the ones who are paying the penalty of this genetic defect are the men who have to content with the only one X chromosome they have.

Why MAO A and MAO B? Why there is not only one enzyme instead of these two very similar enzymes? Why did natural selection let them be? Remember that MAO A and B were split off from just one MAO. The enzyme, which is one in number in aquatic vertebrates, duplicated in transition to mammals? What features does Ancestral MAO show when it is compared with modern enzymes? Is it possible for some other enzymes like MAO C and MAO D to appear? Or do they exist yet we are not aware of them?

Just as Rocky’s victory over his genetically superior opponent Ivan Drago, maybe the aggressiveness that depends on both genetic and environmental factors affected the balance between individuals. The individual who does not appear to be very strong may gain the power to overcome his rival with aggression and passion. With this manner he may have adapted to the environmental conditions and despite of being genetically defected, by starting (and protecting) a family, he might have resisted natural selection and maintained his kind. Understanding how and why these enzymes originated, without a doubt, is a big step to take them under control.

Evolutionary studies seem to teach us lessons about why it would not be fair to judge people just by looking into their genes, what do you think? There is no genome without error, love me with my mutation!

18 March 2010

On the role of MAO

I've waited so long to write this post. Now looking back, MAO actually turned out to be a banned word in Counter Minds. Funny, I worked on this protein for 5+ years and I never (even once) mentioned it here. What does that tell you about my project?

Yes, it was hard. Oh well, they all are. But I guess I've reached a point where I wanted to remind myself why I do science at all. I had to remember that science is not all about troubleshooting assays and charging protein columns or running gels over and over again. So, thanks science blogging world for keeping me on track and for constantly nourishing my love of science!

Anyhow, I paid my dues and signed the reconciliation pact with my doctorate project. It is the time now, to dig up the hatchet, therefore introducing you "The MonoAmine Oxidase" aka the warrior gene.
Yes fellas, Monoamine Oxidase (MAO) is the enzyme that degrades the primary amine neurotransmitters (i.e. dopamine, serotonin) in your body. That means, if you stop the enzyme with a drug, you will burst the amount of the respective neurotransmitters.

MAO-stoppers, known as inhibitors are one of the oldest class of anti-depressants for this reason. Even before the SSRIs, MAOs existed.

Humans carry two forms of MAO: MAO-A and MAO-B. Overall they do the same job, they look the same and they are highly identical to one another. But if you think that enzymes are like human mouth, well, they both eat different type of foods - in a similar way.

Which is one of the reasons why it is so hard to develop better drugs for these two enzymes. You've got two enzymes to target when you get to design 'one' drug. Which is where I came in...

Introducing Zebrafish MAO (aka the enzyme that got me graduated)

Evolutionarily, if mammals ended up having 2 MAO enzymes, there has to be a time in history where only one form existed. [friendly note: This is of course, if you accept evolution. If you don't, please take a deep breath, stretch your mind and keep reading until you see it yourself.]

We shall call that single form, ancestor MAO. And that form, is Zebrafish MAO (zMAO) my dear readers. Here is how the tree explains it:
Knowing that zebrafish is a cheap alternate of common pharmacy-friendly mammals, such as rat and mice, this information is very handy and practical for the sake of drug developments- or so we thought.

I used a yeast system to obtain more and more (you may say shitload) of this protein so we could obtain the x-ray structure. Through my journey, I developed a cloning, expression and purification for this enzyme where I got to publish here: Expression of zebrafish (Danio rerio) monoamine oxidase (MAO) in Pichia pastoris: Purification and comparison with human MAO A and MAO B The hard core enzymology work is about to be out and hopefully the crystal structure will be available soon, as well (which is of course now a part of somebody else' s project, in a galaxy far far away).

What did I find?

I found that the single form of this enzyme is behaving like both human A and B forms. Not surprisingly, it is like a hybrid form of this enzyme. Unfortunately, because of this property, zebrafish models can not be 'directly' used to study MAO, but considering the many other cellular pathways that MAO is involved, the results are still promising.

How is MAO linked to aggression? What makes me type "oh that #$#$#$%#%$#^%$&^%". We will all see why, next time.

03 March 2010

Evolution of a scientist


This is Murat's interpretation of my evolution: A single cell organism develops arms, legs and a bit of skepticism and finds its way to the lab!

21 January 2010

After a long break, I am back!

It has been a really long time since I wrote something here. Many remarkable things have happened in the blogging world during my silence. Such as Richard Dawkins' mention of our very own hardworker for evolution, Uygar Polat's review of The Greatest show on Earth and Science Online 2010, the major meeting event for those of us who absolutely love online science-ing.

I did not make it to Science Online this year and this is why (yeah we all have important reasons reserved for ourselves). But I promise to be there next year!

Thanks to superb communication and outreach skills of sciblings, I did not feel that I was not there though! I even have a favorite moment of the conference! That's right, it is Carl Zimmer and BoraZ, push and pull strategies for science communicado!

[Another good news is that I finally published (some) of my dissertation work. So, here is to you StephanieZ, my essay on 'why humans need two mao enzymes to deal with aggression' is coming soon!]

20 October 2009

Evolution is not allowed here

I was excited after reading a post that seeks volunteers for a high school science event, taking please at my research institute this weekend. Now that I am a Ph.D. and working for the government in a government institute, I thought 'this is the perfect place to give back to society' , and since I am a big fan of education and I believe in the power of education more than anything else, I jumped in.

Yet my excitement did not last for too long. After learning that I work on an evolution project and that's what I would like to talk to with high schoolers, the organizers emailed me the following:

"Any sort of evolution topic is not something we want to introduce at such an event. However, if you have something cool related to astrobiology that you think the kids could understand, we would love to hear the idea!"

You don't want to introduce evolution? If I have something cool related to astrobiology, that's fine? How is that even possible without even mentioning "any" evolution topic? What is the point here? High school students are paying a visit to a scientific research institute to learn, to ask and to see "things" and we can not even mention evolution for some unknown reason? Where else will the students learn about this? In church?

Frustrating.. And wrong. What else can I do but 'hoping' that the system will evolve -faster- to allow evolution?


This is not something I expected in my first month after doing hands-on evolution research. Let's see what'll come next.

20 September 2009

"Take your dirty Atheistic hands off of my school!"

For real.. What a terrible way to start a Sunday morning...




I will write more on this, but for now, here is what this video reminded me of: (Thanks to Mike H.)




"Damn atheists! They are everywhere!"



Is this a joke?