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