Molecular managers call the shots


Scientists are finding that on a molecular level organisms often function like social institutions. Some employ a military-like chain of command while in others important decisions are made by genetic middle managers. The more complex the organism, the less autocratic and more democratic the biological networks appear to be. In most cases, interactions between middle managers are more critical than actions from the “boss.”

YALE (US)—Similar to the way things work in social hierarchies, some molecular organisms give orders and some carry them out.

Knowing these organizational rules will help understand biological systems and social interactions, says Mark Gerstein, A.L. Williams professor of biomedical informatics, molecular biophysics, and biochemistry and computer science, at Yale University.

Gerstein analyzed the regulatory networks of five diverse species, from E. coli to human, and rearranged them into broad leveled hierarchies, including “master regulators,” “middle managers,” and “workhorses.”

In most organisms, he says, master regulators control the activity of middle managers, which in turn govern suites of workhorse genes that carry out instructions for making proteins.

Details of the study were published online in the Proceedings of the National Academy of Sciences.

As a general rule, the more complex the organism, the less autocratic and more democratic the biological networks appear to be, Gerstein says.

In both biological systems and corporate structures, interactions between middle managers are often more critical to functioning than actions by bosses.

“If my department chair takes another job, the emphasis of my lab might change, but it will survive,” Gerstein explains. “But if my systems administrator leaves, my lab dies.”

In simple “autocratic” organisms such as E. coli, there tends to be a chain of command in which regulatory genes act like generals, and subordinate molecules “downstream” follow a single superior’s instructions.

But in more complex “democratic” organisms, most of these subordinate genes co-regulate biological activity, in a sense sharing information and collaborating in governance.

Organisms that have both qualities are deemed “intermediate.”

The interactions in more democratic hierarchies lead to mutually supporting partnerships between regulators than in autocratic systems, where if one gene is inactivated, the system tends to collapse.

This is why Gerstein and colleagues in earlier work found that when they knocked out a master regulating gene in a complex organism, the “effects were more global, but softer” than when a key middle manager gene in a simpler life form was inactivated, which led to the death of the organism.

“Regulators in more complex species demonstrate a highly collaborative nature. We believe that these are due to the size and complexity of these genomes.”

As an example, Gerstein says about 250 master regulators in yeast have 6,000 potential targets, a ratio of about one to 25, compared with humans, in which 20,000 targets are regulated by about 2,000 genes, a ratio of one to 10.

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  1. Frances Morey

    Very interesting. My emphasis is on hydration. All chemical reactions take place in a liquid matrix. If the person is dehydrated many critical reactions won’t proceed. I drink two quarts of herbal tea a day–seems to serve me well. I consider it essence of vegetation containing minute quantities of unknown enzymes that further the ends of the body’s chemical business.

  2. Walter Park

    “Interesting!” as my high school English teacher would say before she said, “However…”

    But i’m surprised at the heavy anthropomorphization. Molecules don’t have bosses, systems administrators, or ‘democracies.’ Why make that stretch?

    I’m happy enough with the mathematical elegance of the interactions.

    There seems to be some sort of backward rationale: not to make the phenomena easier to understand (The one chart included here tells it clearly, i don’t need arrows to be called managers to get it), but to imply the reverse: ‘democracy’ is more sophisticated than autocracy? Don’t need that either.

    Today’s April 1. If you’re just having fun, well, fine!!
    And i’m sure your non-critical-path department chair will keep that in mind while she works on next year’s budget!

  3. Roy Niles

    My guess would be it’s more of an assessment process than administrative, with the hierarchy involving the optional choice steps in the strategic scaffolding.

  4. Jim White

    enviornment and experience squard, the molecular mangers goes from a 5yr old cowboy to capes and swords as a uniform of bouhood to a 18 year old warrior camouflaged, banadanns and rifle, say in the USMC culture to a 25 year old husband king of castle with his princess he travels in quest along with culture to a 60 year old wise old sage granddad as a culture…and is it the same manager during this journey? is it the same demoracy supervising molecular in this journey? is it the same wisdom molecular the whole of ones experience? Or do the molecular change as the journey changes the person in a growth of enviornments and experiences, so squared? Since men “long” do these moleculars spark longings? and change positions? Is it the molecular that heals first or is its one’s mental spirit that heals a wound firstly? Is the molecular the holloween costume or the idenitity? …fasinating…

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