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.


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