Proposal to generate a draft assembly of the compact elephant shark genome

2 Introduction Cartilaginous fishes (Chondrichthyes) are the most basal extant jawed vertebrates that diverged from the common ancestor of tetrapods and teleost fishes (Osteichthyes) approximately 530 Myr ago (Kumar and Hedges, 1998; Fig.1). Cartilaginous fishes possess a body plan and complex physiological systems that are typical of all jawed vertebrates, but are lacking in the jawless vertebrates (e.g. lampreys and hagfishes). They therefore constitute an important basal vertebrate 'reference genome' that can help us better understand the structure, function and evolution of human and other vertebrate genomes. Cartilaginous fishes are a monophyletic group comprising two sister groups, the elasmobranchs (sharks, rays and skates) and the chimeras (Kikugawa et al., 2004; Fig.1). A major impediment to the characterization of genomes from cartilaginous fish is their large size. The dogfish shark (Squalus acanthias), nurse shark (Ginglystoma cirratum), horn shark (Heterdontus francisi) and little skate (Raja erinacea), which are all subjects for biological research, have genome sizes that range from 3.5 Gb to 7 Gb (Hinegardner, 1976; Schwartz and Maddock, 2002). Measurements of genome sizes for cartilaginous fishes have indicated that chimeras have smaller genomes than the elasmobranchs (Hinegardner, 1976; Stingo, 1979). Among the chimeras, we have identified the elephant shark (Callorhinchus milii) as having the smallest known genome (Venkatesh et al., 2005). Based on FACScan flow cytometry and survey sequencing of the genome (see below), we estimate the size of the elephant shark genome to be less than 1 Gb, at least 3 times smaller than the human genome. In contrast, the only other cartilaginous fish that is currently being considered for genome sequencing, the little skate (Raja erinacea), has an estimated genome size of approximately 3.5 Gb (http://www.genome.gov/10002154; Schwartz and Maddock, 2002). Thus, the elephant shark is an attractive candidate for yielding an economical and high-quality sequence assembly of a cartilaginous fish genome. The value of such an assembly for annotation and interpretation of the human genome is discussed below.