Approximate Search on Protein Structures for Identification of Horizontal Gene Transfer in Bacteria Swetha Billa 1 , Mark A. Griep 2 , Peter Z. Revesz 1,* 1 Department of Computer Science and Engineering and 2 Department of Chemistry University of Nebraska-Lincoln *To whom correspondence should be address: revesz@cse.unl.edu Abstract Horizontal Gene Transfer (HGT) is defined as the movement of genetic material from one strain of species to another. Bacteria, being an asexual organism were always believed to transfer genes vertically. But recent studies provide evidence that shows bacteria can also transfer genes horizontally. HGT plays a major role in evolution and medicine. It is the major contributor in bacterial evolution, enabling species to acquire genes to adapt to the new environments. Bacteria are also believed to develop drug resistance to antibiotics through the phenomenon of HGT. Therefore further study of HGT and its implications is necessary to understand the effects of HGT in biology and to study techniques to enable or disable the process based on its effects. Methods to detect HGT events have been studied extensively but no method can accurately detect all the transfers between the organisms. This paper presents an HGT identification method based on approximate searches on bacterial protein structures. This method makes use of Z- score similarities between the protein structures and also uses functions of BLAST and DaliLite to work with protein sequence and structural similarities. In addition, Jmol, a java viewer tool is used for visual structural comparisons and sequence alignment. We also present experimental results regarding HGTs between the Firmicutes bacterium Bacillus subtilis and various Proteobacteria bacteria. 1. Introduction Horizontal gene transfer (HGT) or lateral gene transfer is the passing of genetic material from one organism to another, other than by descent in which genetic Copyright © 2011, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved. information travels through the generations as the cell divides. In nature, gene transfer occurs between two same species or closely related species via typical routes of reproduction, such as cross pollination of plants and interbreeding of animals. Such transfer is also called vertical gene transfer, since traits are passed on from parent to the offspring vertically. Sometimes genes also move between different species, such as bacteria and plants, through a process unrelated to reproduction that is known as horizontal gene transfer (HGT). HGT can also occur between two closely related species. HGT has first been described in a Japanese publication in 1959, which describes about the transfer of antibiotic resistance from one bacterium to another (Akiba et al. 1960). The phenomenon of HGT is quite significant in prokaryotes and some unicellular eukaryotes. Importance of HGT in the evolution of multicellular organisms has not been extensively studied. 1.1 How to determine HGT? For a successful natural horizontal gene transfer, it would require stable integration of the gene into the genome, no disturbance of regulatory or genetic structures, expression and successive production of a functional protein (Susanna et al. 2006). There are two approaches to determine Horizontal Gene Transfer in a genome, I) Phylogenetic Comparison and II) Parametric Comparison. In Phylogenetic Comparison, different organisms are compared to find the similarity or dissimilarity. While in Parametric Comparison, genes that appear to be anomalous in their current genome context are thought to have been transferred or introduced from a foreign source (Lawrence and Ochman 2002). 1.2 Why is it important to study HGT? 18 Proceedings of the Ninth Symposium on Abstraction, Reformulation and Approximation