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By Hayley Mann | March 11th 2009 12:19 PM | 8 comments | Print | E-mail | Track Comments
About Hayley

In 2006, I graduated from UC Davis with a degree in Genetics and Anthropology. I've had the privilege of working for various laboratories conducting...

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Because of the importance of computational genomics, I am writing this article with utmost urgency in hopes of unifying geneticists and biochemists once and for all. 

As a geneticist, I feel that I’m more equipped to write this plea for unification because I see what’s truly and fundamentally on the inside of this dispute, as opposed to biochemists, who are more used to focusing on the external and therefore superficial aspects of things. 

I'd like to break this dispute down to a science by comparing the two fields. 

By traditional definition, genetics is the study of heredity while biochemistry is the study of the chemistry of life.  Often, geneticists and biochemists are seeking answers to the same highly complex questions.  However, approaches are very different and therein lay the dispute; what approach is truly best?  Starting from the nucleus of a cell and working your way out?  Or starting from the outside of the nucleus and working your way in?  Perhaps a better way of phrasing it would be, is it best to truly get to know an organism by looking deep into its genome and then evaluating its character?  Or is it best to draw conclusions from judging an organism based on its phenotype? 

To illustrate the difference in approaches, let’s discuss a simple hypothetical experiment in detail.

We must first select the proper organism to research.  I'm used to experimenting on creatures with faces, but since I have an option and I am in a kind mood I’ll choose Saccharomyces cerevisiae or, rather, "yeast."   The aim of our hypothetical experiment is to determine if S. cerevisiae gene X and gene Y interact in the same pathway.

In biochemistry, if gene X and gene Y interact then protein X and protein Y will interact in the same biochemical complex.  In order to determine protein interaction, protein complex immunoprecipitation (Co-IP) followed by a SDS-PAGE gel analysis can be performed.  For Co-IP, an antibody is used to probe cell extract that contains numerous proteins for one specific protein.  With the antibody now attached to the protein of interest, the sample can be spun down and the antibody-protein product can be isolated for further analysis.  If protein X and Y are interacting, then it can be visualized in a SDS-PAGE gel.  

Often, several unknown proteins are discovered that are involved in the complex as well.  However, if protein X truly interacts with protein Y, then no matter what specific antibody you initially probe the cell extract with the protein interaction will always be observed in the SDS gel. 

Typically, to verify gene interactions in biochemistry it takes several exhausting rounds of Co-IP followed by SDS-Page gel analysis.

In genetics, in order to deduce gene X and Y interaction, different yeast mutants that contain nonfunctional gene copies can be constructed via transformation.  These mutants along with wildtype strains are then crossed and offspring phenotypes are scored.  In the case of yeast, we can observe prodigy typically by the next day.  Thankfully this type of experiment yields a definitive answer, so no repeat rounds are necessary and the geneticist will make it to Yoga by 4:30 no problem.

I found a paper from 2005 (Wong, et al.) that statistically compares the accuracy of genetics and biochemistry approaches.  The paper also answers our original question; which approach is superior?  The answer may surprise you. 

The genetics approach was shown to be the best way to infer relationships between interacting genes (there were other comparison papers too but I found that this one illustrated my point best).

I know it's a crushing blow biochemists.  And that's hurtful because the facts don't lie.  I realize that you feel inadequate and you're very angry.  But biochemists, please, I beg of you, put your pain aside and cooperate because, in truth, our fields are highly intertwined; you need my genes to create proteins so you have something to study in the lab.  If that doesn't persuade you then this will:  Wong et al., 2005 also suggests that when we pool our two approaches together we obtain the greatest accuracy in results. 

Since we're all being honest with each other, I will tell you I’m actually not thrilled at the idea of unification either because, like all scientists, I prefer to publish papers with a single authorship name.  But just like Wong et al., 2005 figured out, computational genomicists have also discovered that our two fields combined yield more accurate results.  Therefore, I can’t help but feel the overwhelming need to unite since in this economy, surely we can't afford to lose our jobs to droids.


References:

Wong, SL., Zhang, LV. and Roth, FP. 2005.  Discovering functional relationships: biochemistry versus genetics. Trends in Genetics. 21(8): 424-425.

 



Comments

Hank's picture
It took me 10 minutes to figure out that graphic.   Was Dali a scientist?   I don't know what is going on there but I am going to keep looking.

Gerhard Adam's picture
I think it's simply the Dali version of "can't we just all get along?"

Alternate Allele's picture

It's a Double Helix representing team "Geneticist" and a Protein representing team "Biochemistry."  (Notice how the Double Helix has the Protein-dude in a choke hold.)  But regardless of who's winning in journal articles or wrestling, we all just need to get along and that's clearly defined by the red X in the graphic.

However, Dali is my favorite artist so I'm going to take that critique as a compliment to my superior graphics design work.



adaptivecomplexity's picture
You've laid down the gauntlet! 
As someone with a PhD in biochemistry, working in a genetics department, I'm conflicted. Well, not really: Fritz Roth, when he wrote this paper, had this classic conflict in mind: Biochemistry vs. Genetics - the case of Doug and Bill.

On a hill overlooking an automobile factory, lived Bill, a retired geneticist, and a retired biochemist (nobody knew his name). Having spent a life in pursuit of higher learning, both were wholly unfamiliar with how cars worked, and they decided that they would like to learn about the functioning of cars. Having different scientific backgrounds they each took a very different approach. Bill, not being inclined towards hard work (like most geneticists), immediately came up with a scheme that he thought would lead him to an understanding of cars. The next morning he went down the hill and tied the hands of one of the workers in the factory. He then went back up the hill and sat down to a cup of coffee. As he was just starting to sip his cup of coffee, he heard some banging noises and went out to the garage to see what was going on. When he looked in the garage he found that the biochemist had gotten one of the cars from the factory and was already covered with grease and oil as he was doing something under the hood. When Bill asked the biochemist what he was doing, he replied: "I'm taking the car apart to see how it works". The geneticist laughed and then sat down to enjoy his cup of coffee while he made fun of the biochemist. Bill spent the entire day drinking coffee while the biochemist struggled and sweated under the hood of the car.''...


In the end (of this version of the story anyway - it's the biochemistry version), when geneticist Bill's car breaks down, he's helpless - until the biochemist Doug comes by and fixes it.
The genetics approach was shown to be the best way to infer relationships between interacting genes

It's funny, geneticists talk big like this, but they always want the biochemistry in the end. I recently submitted a paper to a genetics journal (which shall remained unnamed, but let me say, I hate PLoS...). In the paper I showed that, when you delete a particular gene, other genes get switched on - in other words, I had identified a genetic repressor.

The genetics reviewers were unsatisfied with this - they didn't care that it was a repressor in the genetic sense; they wanted to see the biochemistry.  Even geneticists aren't happy until you get to the molecular details that only biochemists can get...


logicman's picture
"In the paper I showed that, when you delete a particular gene, other genes get switched on - in other words, I had identified a genetic repressor."

If you can't get that result published, then peer review is acting as a blocking filter. Why not publish on the web?

As to cars and methodologies:
A mechanic with an engineering degree will know about stresses in metals and their design implications. He or she, unlike the amateur, having removed the four visible bolts on a casting, will not then resort to hammer and screwdriver, but will seek to determine where the one remaining bolt is hidden.

adaptivecomplexity's picture
It's published - but I was amused that a genetics journal (not the one I ended up publishing in) didn't really like genetics.

logicman's picture
Your "regulatory interactions" is how I understand the mechanism of how words are strung into sentences to conform to social usage norms. (Grammar? Who needs it?)
As for the rest of the abstract, I get the gist of it, but it's way over my head. :)

Seriously, though, I wish you every success with your research.

adaptivecomplexity's picture
Thanks.
It's funny how different fields can use the same words, but with completely different meanings, making writing in one field unintelligible to a specialist in another field. I get completely lost when it comes to linguistics. 

It's good to avoid jargon, but when you've got to accurately summarize the paper in 300 words, there's no way around it if you want to be precise.


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