Professor of Chemistry
Ph.D.| University of California, Los Angeles, 1990
Postdoctoral Fellow | The Scripps Research Institute, 1990-1993
Postdoctoral Fellow | University of Oregon, 1993-1995
My research is focused on the biochemical and genetic issues involved with the origins of life on the Earth. As an evolutionary biochemist, I am interested in applying the same principles that govern the changes over time in modern populations of organisms to the populations of molecules that comprised the "primordial soup" from which life self-organized some 4 billion years ago. A current scenario for the origins of life postulates a time when all metabolic and information-flow processes were carried out by RNA molecules, as opposed to today, when proteins and DNAs primarily hold these responsibilities. This hypothetical time is called the RNA World, and draws much support from the wide variety of catalytic RNAs (ribozymes) that have been discovered to date.
Our research has two central themes. One is the role of recombination in the RNA World, and the other is the role of divalent metal ions in ribozyme-directed catalysis. Regarding the former, we are interested in the advantages that recombination (the swapping of large blocks of genetic information) could have played during the advent of life. We are investigating both the benefits that recombination gives for the creation of new genetic diversity and the protection that recombination provides against the accumulation of deleterious mutations in an otherwise adapted population of RNA molecules. To these ends, we have engineered the Azoarcus group I intron to be an effective RNA recombinase: it can recombine RNA fragments to construct new RNA sequences, including hammerhead, ligase, group I ribozymes, and importantly, itself (Riley & Lehman, 2003; Hayden et al. 2005; Hayden & Lehman, 2006). We are also using continuous evolution in vitro (Wright & Joyce, 1998; Science 276: 614-617) to test how rapidly RNA populations build up deleterious mutations and how effective recombination can be in preventing this from happening.
Regarding the latter, our lab uses evolution in vitro ("evolution in a test tube") to mimic the evolutionary process as it occurs in natural populations to explore the range of divalent catalysis available to different ribozymes. We are interested in the biochemical modifications and adaptations required to coax Mg(II)-dependent ribozymes to use other metals such as Ca(II), Sr(II), and Zn(II). Some ribozymes are malleable in this regard, while others are not, and we are using evolution in vitro coupled with a variety of standard biochemical techniques to elucidate patterns in ribozymology (Burton & Lehman, 2006).
- Vaidya N, Manapat ML, Chen IA, Xulvi-Brunet R, Hayden EJ, Lehman N (2012). Spontaneous network formation among cooperative RNA replicators. Nature 491:72-77.
- Diaz Arenas C, Lehman N (2010). Quasispecies-like behavior observed in catalytic RNA populations evolving in a test tube. BMC Evolutionary Biology 10: 80.
- Vaidya N, Lehman N (2009). One RNA plays three roles to provide catalytic activity to a group I intron lacking an endogenous internal guide sequence. Nucleic Acids Research 37: 3981-3989.
- Hayden EJ, von Kiedrowski G, Lehman N (2008). Systems chemistry on ribozyme self-construction: evidence for anabolic autocatalysis in a recombination network. Angew. Chem. Int. Ed. 47: 8424-8428.
- Zenisek SM, Hayden EJ, Lehman N (2007). Genetic exchange leading to self-assembling RNA species upon encapsulation in artificial protocells. Artificial Life 13: 279-289.
- Soll S, Diaz Arenas C, Lehman N (2007). Accumulation of deleterious mutations in small abiotic populations. Genetics 175: 267-275.
- Hayden EJ, Lehman N (2006). Self-assembly of a group I intron from inactive oligonucleotide fragments. Chemistry & Biology 13: 909-918.
- Burton AS, Lehman N (2006). Calcium(II)-dependent catalytic activity of the Azoarcus ribozyme: Testing the limits of resolution for in vitro selection. Biochimie 88: 819-25.
- Hayden EJ, Riley CA, Burton AS, Lehman N (2005). RNA-directed construction of structurally complex and active ligase ribozymes through recombination. RNA 11:1678-1687.
- Lehman N, Unrau PJ. Recombination during in vitro evolution (2005). Journal of Molecular Evolution 61:245-252.
- Lehman N (2004). Assessing the likelihood of recurrence during RNA evolution in vitro. Artificial Life 10: 1-22.
- Riley CA & Lehman N (2003). Generalized RNA-directed recombination of RNA. Chemistry & Biology 10: 1233-1243.