NASA Astrobiology Institute (NAI)

2009 Nobel Prizes – The Origin of Life Connection

A number of Nobel Prize winners became actively interested in the origins of life at some point in their careers. Among them are Ernst Schrodinger, Jacques Monod, Harold Urey, Manfred Eigen, Christian de Duve, Albert Eschenmoser and Baruch Blumberg. This year, however, for the first time, two scientists who have already made important contributions to origins of life research received Nobel Prizes. They are Jack Szostak from Harvard Medical School and Ada Yonath from Weizmann Institute.

Jack Szostak received the Nobel Prize in Physiology or Medicine for his work on telomeres, conducted largely in the 1970’s and 80’s. For more than the past 20 years he has been involved in studies of the origins of life. His early work in this area was focused on in vitro evolution of RNA molecules. In 1993 he and David Bartel evolved the first RNA enzyme (rybozyme) from a pool of random-sequence RNAs [1]. This rybozyme catalyzed the ligation of an oligonucleotidesubstrate to the 5’ end of the ribozyme, directed by an internal template region. This reaction was of special interest because of its similarity to the reaction carried out by an RNA-dependent RNA polymerase.

A few years ago Jack extended the in vitro evolution technique to proteins. Using this approach he and Tony Keefe obtained the first simple, functional protein with no biological ancestry [2]. Subsequent experiments demonstrated that proteins unrelated by sequence or structure can carry out the same function and, conversely, the same simple structure can be mutated to perform different functions [3,4]. This work, funded mostly by the NAI, not only sheds new light on the origin of protein diversity but also holds great promise for biotechnology.

Most recently, Jack’s research efforts have concentrated on constructing synthetic cellular life in the laboratory in order to understand possible pathways leading to the origin of life. His basic design involves the encapsulation of a spontaneously replicating nucleic acid, which acts as the genetic material, within a spontaneously replicating membrane boundary, which provides spatial localization [5]. A membrane-bound vesicle system thus undergoes repeated growth and division without the involvement of any biochemical machinery and is permeable to activated monomers. The vesicle-contained nucleic acid polymers contain modified nucleobases and sugar-phosphate backbones to improve speed and accuracy of replication without enzymatic assistance. This system should be able not only to self-replicate, but also to undergo Darwinian evolution.

For many years, Jack has been participating in the NASA Astrobiology program as a principal investigator in the Exobiology and Evolutionary Biology Program and a member of the NASA Ames team of the NAI. He was an invited speaker at many origins of life conferences. Most recently, he delivered the Orgel lecture at the ISSOL meeting in Florence and was the keynote speaker at the Origin of Life Gordon Conference in Ventura. An excellent exposition of his work and views on the origin of life can be found in the September issue of Scientific American and in an NAI Director’s seminar presented in November 2008 and archived on the NAI website at http://astrobiology.nasa.gov/nai/seminars/.

Ada Yonath received this year’s Nobel Prize in chemistry for her contribution to understanding the structure and function of the ribosome. In the early 1980’s she was the first to obtain crystals of the 50S subunit of the ribosome [6] and spent the next 25 years elucidating the ribosome’s structure and mechanism of action. As a part of this effort, Ada studied evolution of the ribosome to understand the origins of modern translation machinery. On the basis of structural, biochemical, mutagenesis and computational evidence, she arrived at the conclusion that the modern ribosome evolved from the proto-ribosome, a small, dimeric RNA assembly formed through gene duplication. This proto-ribosome was endowed with a symmetrical pocket that was capable of catalyzing both peptide bond formation and non-coded amino acid polymerization. This pocket remains embedded in the core of the modern, universal ribosome and is required for its catalytic function.

Recently, the origin of life community had an opportunity to hear about Ada’s work at several conferences, including last year’s ISSOL meeting in Florence and the workshop on Open Questions in the Origin of Life held earlier this year in San Sebastian. Her most recent views on the origin of the translation machinery can be found in a review that will appear shortly in the special issue of Research in Microbiology devoted to the origin of life [7]. This paper is already available on line.

We congratulate Ada and Jack on their awards. We also hope that they will remain actively involved in origins of life research. Their achievements demonstrate the great scientific potential of studies aimed at linking prebiotic chemistry with modern biology.

References:

[1] Bartel DP, Szostak JW. (1993). Isolation of new ribozymes from a large pool of random sequences. Science 261, 1411-1418.
[2] Keefe AD, Szostak JW. (2001). Functional proteins from a random sequence library. Nature 410, 715-718.
[3] Cho GS and Szostak JW. (2006) Directed evolution of new Zinc-finger ATP-binding proteins using mRNA display, Chem Biol., 13, 139-47.
[4] Seelig B, Szostak JW. (2007). Selection and evolution of enzymes from a partially randomized non-catalytic scaffold. Nature 448:828-31.
[5] Szostak JW, Bartel, DP and Luisi, PL. (2001). Synthesizing Life. Nature 409, 387-390.
[6] Shevack, A., Gewitz, H.S., Hennemann, B., Yonath, A., and Wittmann, H.G. (1985). Characterization and crystallization of ribosomal particles from Halobacterium marismortui. FEBS Lett 184, 68-71.
[7] Davidovich, C., Belousoff, M., Bashan, A. and Yonath, A. (2009). The evolving ribosome: from non-coded peptide bond formation to sophisticated translation machinery,
Res. Microbiol., in press (available in prepublication).

Written by Andrew Pohorille, edited by Carl Pilcher.

Oct 15, 2009

Rafal Wieczorek said:

Albert Eschenmoser is a great organic chemist, who received numerous prizes for his work, most notable vitamin B12 synthesis. If he received Nobel prize, it would be certainly deserved. However, up to this day, he didn’t. Just a correction.