9318594 PALMER The peroxisome is a small, membrane-bound organelle found in the cells of all animals and other higher organisms. Peroxisomes lack a genome of their own, but a number of important biochemical reactions and enzymes (coded for by nuclear genes) occur within the peroxisome, and a large number of human diseases, mostly lethal, are caused by defects in peroxisomal function. Although much is known about the function of the peroxisome, we know nothing about its origin. This project seeks to remedy this situation by gathering evidence to test the two competing hypotheses for the origin of the peroxisome: 1) that it arose by internal compartmentation of a subset of metabolic enzymes, or 2) that, like chloroplasts and mitochondria, it arose endosymbiotically, i.e. by the permanent uptake of a bacterium (which turned into the peroxisome) by a primitive eukaryotic cell. In preliminary studies, we have identified four peroxisomal proteins that show provocatively high levels of similarity to bacterial homologs, and which thus provide suggestive evidence in support of hypothesis #2. To provide a rigorous test of the endosymbiotic hypothesis of peroxisomal origins, we will sequence and phylogenetically analyze the genes for each of these four proteins from about 20 diverse bacteria and from several representative eukaryotes. In addition, we will sequence several other genes, such as those encoding for the heat shock proteins, as they become available to this project. In the absence of a peroxisomal genome, it is imperative that congruent data be sought for as many different peroxisomal proteins as possible. The strongest answer to the question "Is the peroxisome an endosymbiont?" will come if multiple nuclear genes for peroxisomal proteins all trace back to the same place within a bacterial phylogenetic tree, a place distinct from that of both mitochondria and plastids. If such an answer is forthcoming, it would provide a rationale for reassessing the possibility that a residual perox isomal genome might still lurk in some eukaryotes. This project is being jointly funded by the Systematic and Population Biology programs of the Division of Environmental Biology (DEB) and the Metabolic Biochemistry program of the Division of Molecular and Cellular Biosciences (MCB). %%% Peroxisomes are small cellular organelles that are very important to the metabolism and effective functioning of cells. Several lethal human diseases are attributed to defects in peroxisomal functioning. This study will investigate the origin of these important organelles. ***
