James Lake, Ph.D.

Work Address:
Los Angeles, CA 90095 MBI 242
Los Angeles, CA 90095

Distinguished Professor, Molecular, Cell, and Developmental Biology, Human Genetics
Member, Basic/Translational Research, Jonsson Comprehensive Cancer Center, Bioinformatics GPB Home Area, Genetics & Genomics GPB Home Area
Research Interests
Our lab is interested in Genomic Evolution. We want to understand the evolution and origin of eukaryotes and the origin of life, and want to relate its evolution to the molecular, cell and developmental events that have occurred. Specific interests are described below. Prokaryotic Ancestors of Eukaryotes A fundamental challenge in biology is to discover the origins of the eukaryotic cell. We are searching for the immediate prokaryotic relatives of the eukaryotes. Recently our lab has made a major breakthrough, and obtained evidence that the eukaryotic genome is the result of an ancient genome fusion between an eubacterium and an archaebacterium (Rivera & Lake, Nature, 2004). The strongest evidence to date is that an archael eocyte (sulfur metabolizing, hyperthermophilic bacteria) fused its genome with a eubacterial proteobacterium to form the first eukaryote. This view pioneered by our lab has recently obtained very strong experimental support from other labs (as discussed in ?On the Origin of Eukaryotes?, Carl Zimmer, Science, 7 August 2009, vol. 325, 666 ? 668). Given the powerful new computational tools being developed, we can now start to view accurately the early evolution of life on Earth. Evidence for Early Prokaryotic Endosymbioses Endosymbioses have dramatically altered eukaryotic life, but were thought to have negligibly affected prokaryotic evolution. However, by analyzing the flows of proteins families, our lab has recently obtained evidence that the double-membrane, Gram-negative prokaryotes were formed as the result of a symbiosis between an ancient actinobacterium and an ancient clostridium (Nature, J. Lake, 20 August 2009, vol. 460, 967-971). The resulting taxon has been extraordinarily successful, and has profoundly altered the evolution of life by providing endosymbionts necessary for the emergence of eukaryotes and by generating Earth?s oxygen atmosphere. Their double-membrane architecture and the observed genome flows into them suggest a common evolutionary mechanism for their origin: and endosymbiosis between a clostridium and actinobacterium. Our lab is intensively focusing on using new techniques to discover other endosymbioses that occurred during Earth?s evolution. Genomic Analyses The computational analysis of genome evolution is still in it?s infancy, and opportunities for new discoveries abound. For example it is becoming obvious that understanding evolution by reconstructing trees does not tell the whole story of evolution. Cells not only divide and multiply, but they also fuse through endosymbioses to form new types of cellular organizations. The tools needed to reconstruct past cell multiplications (tree reconstruction) are available, but the tools needed to detect past fusions (endosymbioses) are being developed in our lab, and the findings are changing our perceptions of life?s early evolution. The Root of the ?Tree of Life? Our lab is also strongly involved in deciphering another unsolved evolutionary/genomic mystery. Namely, we?d like to know what the last common ancestor of life was. Specifically, where did it live, what did it eat, what enzymatic processes did it carry out, and was it thermophilic, or not. We are using indels, insertions and deletions, present in genes to locate the root of the tree, or graph, of life and thereby infer the nature of life?s last common ancestor. By devising new algorithms to find additional indels and to analyze them in novel ways, we are changing many of the traditional ideas about the early evolution of life on the Earth. Our current work is summarized in (Lake, Skophammer, Herbold, and Servin. Genome beginnings: Rooting the tree of life. Phil. Trans. Royal Soc., B, vol. 364, August 2009, 2177-2185).

Jim Lake’s fundamental evolutionary discoveries, like the New-Animal-Phylogeny for which he received the 2011 Darwin-Wallace Medal, combine a deep understanding of biology with transformative genomic analyses. He is breaking new ground rooting the tree of life, reconstructing the eukaryotic rings of life, and providing genomic evidence for ancient prokaryotic endosymbioses. Research Interest: Evolution, Genomics and Bioinformatics, including the evolution and origin of genomes

Lake, J. A. Evidence for an early prokaryotic endosymbiosis. . Nature 2009; 460: 967-971.
Lake, J. A., Skophammer, R. G., Herbold, C. W., and Servin, J. A. Genome beginnings: Rooting the tree of life. . Philosophical Transactions of the Royal Society, Section B 2009; 364(1527): 2177-2185.
Ragan, M. A.; McInerney, J. O.; and Lake, J. A. The network of life: genome beginnings and evolution’. Philosophical Transactions of the Royal Society B 2009; 364(1527): 2169-2289.
Lake, J. A. Reconstructing Evolutionary Graphs: 3D Parsimony. . Molecular Biology and Evolution 2008; 25: 1677-1682.
James A. Lake Disappearing Act. Nature 2007; 446: 983.
Skophammer, R. G., Servin, J. A., Herbold, C. W., and Lake, J. A. Evidence for a Gram Positive, Eubacterial Root of the Tree of Life. . Molecular Biology and Evolution 2007; 24: 1761-1768.
James A. Lake Craig W. Herbold Marica C. Rivera Jacqueline A. Servin Ryan G. Skophammer Rooting the Tree of Life Using Nonubiquitous Genes. Molecular Biology and Evolution 2006; 24(1): 130-6.
Simonson, AB Servin, JA Skophammer, RG Herbold, CW Rivera, MC Lake, JA Decoding the genomic tree of life. Proceedings of the National Academy of Sciences of the United States of America. . 2005; 102 Suppl 1: 6608-13.
Rivera, MC Lake, JA The ring of life provides evidence for a genome fusion origin of eukaryotes. Nature. . 2004; 431(7005): 152-5.
Jain, R Rivera, MC Moore, JE Lake, JA Horizontal gene transfer accelerates genome innovation and evolution. Molecular biology and evolution. . 2003; 20(10): 1598-602.
Simonson, AB Lake, JA The transorientation hypothesis for codon recognition during protein synthesis. Nature. . 2002; 416(6878): 281-5.
Jain, R Rivera, MC Lake, JA Horizontal gene transfer among genomes: the complexity hypothesis. Proceedings of the National Academy of Sciences of the United States of America. . 1999; 96(7): 3801-6.
Lake, J.A., Jain, R., and Rivera, M.C. Mix and Match in the Tree of Life. Science 1999; 283: 2927-2928.