April 2012

Evolution and molecular Lego


Not far from the traffic and cacophony of downtown Bangalore is a quiet, secluded compound that houses India’s National Centre for Biological Sciences of the Tata Institute of Fundamental Research. Now in its 20th year, this center of research excellence is powered by scientists studying biochemistry, biophysics and bioinformatics; cellular organization and signaling; ecology and evolution; genetics and development; neurobiology; and theory and simulation of biological systems. I had the pleasure of visiting the NCBS in February to attend an international workshop and research conference titled The Evolutionary Origins of Compartmentalized Cells. India’s International Centre for Theoretical Sciences provided funding for the meeting as part of its mission to nucleate new areas of research by bringing together scientists from diverse fields.

The conference was organized by Frances Brodsky from the University of California at San Francisco together with Satyajit (Jitu) Mayor and Mukund Thattai from the NCBS. Their goal was to bring together evolutionary biologists, cell biologists and immunologists to try to synthesize what these disciplines can teach us about the origins of the first eukaryotic cell and the origin of the human immune system. The conference taught me an important lesson: Evolution of a biochemical process can teach us a great deal about how it operates – it can help determine which features are fundamental and which represent cellular or organismal specialization. I have often neglected to consider evolution when trying to understand the molecular basis of a given cellular process. Evolution adds an important dimension.

pres_msg_Frances_Brodsky   pres_msg_Satyajit_Mayor   pres_msg_Mukund_Thattai 
  The conference was organized by Frances Brodsky of the University of
  California at San Francisco, Satyajit (Jitu) Mayor, center, and Mukund
  Thattai from India’s National Centre for Biological Sciences.

“Bringing together molecular cell biologists, immunologists and evolutionary biologists who appeared ready to candidly discuss their favorite cellular processes and structures and debate the origins of cellular compartments and cellular immunity in the context of new ideas about genes and their capacity for evolution was a risky experiment for us as organizers of this conference,” said Mayor. “The quality of discussion and the fount of new ideas generated suggest that this experiment was wildly successful. This augurs well for a bright future for the exciting and emerging field of evolutionary cell biology.”

Thattai echoed Mayor’s sentiments, saying, “One of the great things about studying the evolution of cells is that no topic is off limits. Though ours was a diverse meeting by any standard, with topics ranging from organelle biology to phylogenetics to ancient viruses, I found fascinating and relevant ideas to take away from every talk.”

Brodsky added, “Molecular cell biologists interested in the evolutionary origins of pathways we study can learn a lot from immunologists who have refined techniques to extract information from the co-evolution of host–pathogen interaction pathways, which are the most rapidly evolving in biology.”

I was invited to the conference because I share a common experience with one of the organizers, Brodsky. A manuscript referee once told each of us (independently) that the human proteins that we were describing couldn’t be relevant because that gene product is not present in mice (even though it was present in all other vertebrates). Some take the even more extreme view that if we understand a process in yeast it is not worth studying in humans because we already understand the fundamentals.

This cannot be correct: We need to understand the regulation of human pathways that will differ in different cell types, tissues and developmental stages. Many diseases can be attributed to proteins that are found only in humans and for which the genes represent duplication and diversification to yield traits needed for our complex physiology. Thus, the study of human cells and tissues is important; the study of nonhuman organisms and pathogens is also important. When we see convergent evolution provide the same solution to a complex problem, we have a better understanding of its importance.



Minority travel awards are available for each symposium. See the website for deadlines and details about this and other opportunities.


Mitochondria: Energy, Signals and Homeostasis
June 27 – June 29, East Lansing, Mich.

Frontiers in Lipid Biology
Sept. 4 – 9, Banff, Alberta, Canada

Transcriptional Regulation: Chromatin and RNA Polymerase II
Oct. 4 – 8, Snowbird, Utah

Post-Translational Modifi cations: Detection and Physiological Role
Oct. 11 – 14, Tahoe City, Calif.


Molecular Lego
As we obtain more and more protein structures, we see that certain folds are used to achieve distantly related but likely functionally similar processes. Sometimes structure conservation is achieved by gene duplication, but other times convergent evolution appears to come to a common solution. Structural biologists surely know more of this than the rest of us (and I implore them here to please write a review or send one to me); all of us should learn more about this. When we find proteins of unknown function, structurally related proteins may provide us with important clues to how those proteins work. A wonderful example is the structure of certain nuclear pore complex proteins that resemble elements of clathrin transport vesicle coats: They were made up of an alpha solenoid connected to a beta propeller to form a flexible, macromolecular assembly. Transport vesicle tethering factors share this feature; perhaps this is trying to tell us that transport vesicle coats once performed a tethering role.

The conference was enhanced by tutorial lectures by many of the speakers to provide the background information needed for students (and faculty members) from diverse areas to be able to appreciate the topic. This made it possible to include a truly interdisciplinary set of speakers and topics. In times of tight research funding, it may be more important than ever to encourage scientists to organize and attend such combination workshop-conferences. A great way to initiate valuable collaborations is to bring people together and provide them with lots of time to interact with one another and to learn what others are thinking about. Collaboration will continue to be more important when funds are tight, and the best collaborations team scientists from different disciplines who can bring to the table distinct approaches and tools. Meetings can energize us, stimulate new ideas and catalyze the discovery of novel connections between diverse proteins, pathways or systems.

This month, the American Society for Biochemistry and Molecular Biology holds its annual meeting in San Diego, and we are also sponsoring a number of smaller, member-initiated meetings on a variety of topics. We encourage you to help identify cutting-edge, interdisciplinary topics for consideration for ASBMB-sponsored special symposia or annual meeting themes for next year and beyond. In the meantime, I look forward to seeing you in San Diego!

Suzanne PfefferASBMB President Suzanne Pfeffer (pfeffer@stanford.edu) is the Emma Pfeiffer Merner professor of medical sciences and a biochemistry professor at the Stanford University School of Medicine.

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