Our lab is interested in Genomics, Bioinformatics, and Molecular Evolution. We want to understand the evolution of genomes, including the origin of eukaryotes and the origin of life, and want to relate their evolution to the molecular, cell and developmental events that have occurred. Five specific interests are described below.
Origin of the Multicellular Animals
For years scientists have wanted to know how the multicellular animals originated, but the morphological properties they had to work with were not particularly informative. With molecular sequences available, this has changed and we are obtaining sequences and starting to understand their evolution. We would particularly like to understand the separation of the deuterostomes (vertebrates, echinoderms, etc.) from the protostome (fruit flies, nematodes, etc.) groups and to relate it to the evolution of their genomes and developmental plans. (Nature, 1997).
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. The strongest evidence to date is that eocyte prokaryotes (sulfur metabolizing, hyperthermophilic bacteria) are the immediate relatives of eukaryotes comes from the sequencing of elongation factor Tu genes in our lab (Science, 1992). Other recent evidence on the origin of eukaryotes from our lab have been the identification and characterization of an eukaryotic type I topoisomerase in a hyperthermophile, Methanopyrus, and the X-ray determination of a histone complex in Methanopyrus which has the structure of one-half of an eukaryotic nucleosome.
Analyses of complete genomes are providing unprecidented insights into the evolution of eukaryotes and prokaryotes. For example in a recent analyses of complete genomes (Rivera, et al., 1998; Jain, et al., 1999), we showed that both prokaryotes and eukaryotes contain two types of genes, and both types have different inheritances. One class of genes, informational genes (genes primarily involved in translation, transcription, replication, etc.), is a deeply diverging lineage which has been transferred in a tree-like pattern. In contrast, operational genes (genes primarily involved in housekeeping), have been inherited by horizontal transfer. These findings are rapidly changing our perceptions, of the evolution of life, and we are vigorously pursuing genome-level analyses
Our lab is also interested in the computational aspects of genomics. In addition to developing methods for studies of genome evolution, we are also developing tools for the identificaiton of genes within genomes. A particularily difficult problem is the determination of the locations of introns and exons within the human genome. Using novel, mathematically optimal algorithms, we are discovering new methods for analysis of the human genome and are deeply involved in the analysis of syntenic regions common to the human and mouse genomes.
Molecular Sequence Analysis
The computational analysis of gene evolution is still in it?s infancy and yet forms the technical basis for the field of molecular evolution. Our lab is currently working on three different aspects of sequence analysis: phylogeny reconstruction, sequence alignment, and the stochastic nature of sequence analysis. These areas are becoming increasingly important as we try to use sequences to probe deeper and deeper into the past.
Lake, J. A., Larsen, J., Sarna, B., Pu, Y., Hyunmin, K., Zhau, J., and Sinsheimer, J., "Rings Reconcile Genotypic and Phenotypic Evolution within the Proteobacteria", Genome Biology and Evolution 7 (12): 3434-3442 (2015).
Lake, J. A., "Eukaryotic Origins", Phil. Trans. R. Soc. B 370 (2015).
Simpson, L; Douglass, S. , Lake, J. A., Pellegrini, M., and Li, F., "Comparison of the Mitochondrial Genomes and Steady State Transcriptomes of Two Strains of the Trypanosomatid Parasite, Leishmania tarentolae", PLOS Biology (2015). [link]
Rivera, M. C., Maguire, B., and Lake, J. A., "Dissociation of Ribosomes into Large and Small Subunits", Subcellular Fractionation 206-210 (2014).
Rivera, M. C., Maguire, B., and Lake, J. A., "Purification of Polysomes", Subcellular Fractionation 203-205 (2014).
Rivera, M. C., Maguire, B., and Lake, J. A., "Isolation of Ribosomes and Polysomes", Subcellular Fractionation 189-195 (2014).
Rivera, M. C., Maguire, B., and Lake, J. A., "Purification of 70S Ribosomes", Subcellular Fractionation 200-202 (2014). [link]
Rivera, M. C., Maguire, B., and Lake, J. A., "Purification of Ribosomes, Introduction to "Purification of Ribosomes, Ribosomal Subunits, and Polysomes", in 'Subcellular Fractionation"", Subcellular Fractionation 187-188 (2014).
Lake, J. A. and Sinsheimer, J. S., "The Deep Roots of the Rings of Life", Genome Biology and Evolution 5: 2440-2448 (2013). [link]
Sinsheimer, J. S., Little, J. R., and Lake, J.A., "Rooting gene trees without outgroups: EP rooting", Genome Biology and Evolution (2012). [link]
Lake, J. A., "Lynn Margulis (1938-2011)", Nature 480: (2011).
Ragan, M.A., McInerney, J.O. and J.A. Lake, "The network of life: genome beginnings and evolution: Papers of a theme issue compiled and edited by M.A. Ragan, J.O. McInerney and J.A. Lake", Philosophical Transactions of the Royal Society B 364 (1527): 2167-2289 (2009).
Lake, J. A., "Evidence for an early prokaryotic endosymbiosis", Nature 460: 967-971 (2009).
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 364 (1527): 2169-2175 (2009).
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 364 (1527): 2177-2185 (2009).