Within the Mollusca, cephalopods diverged from a monoplacophoran-like ancestor over 500 million years ago, later branching into the extant clades Nautiloidea (Nautilus and Allonautilus) and Coleoidea (squid, cuttlefish and octopus) [2,42-44]. The CephSeq Consortium has come together with the intention of using strategic genomic and transcriptomic sequencing of key cephalopod species to address previously unanswerable questions about this group. Taking into account the challenges of cephalopod genome sequencing, as well as the necessity to address nodal taxa, we have identified a set of species on which to focus our initial efforts. Selected species have been chosen based on the curiosity of their biological features as well as the possible advantages of their practical use. These species also cover ecologically diverse life histories, representing benthic, nectobenthic and nectonic animals.
Cephalopods are animals with advanced cognitive skills and a complex repertoire of behavioral abilities [3,45]. Their brains are comparable both in size and complexity with those of vertebrates, and have been the focus of a number of studies on the neurobiology of behavior . In particular, they have served as models for the cellular and systems circuitry of learning and memory [4,9]. Historically, Octopus vulgaris has been a key species for this work through studies of anatomy , behavior following lesions and brain stimulation [3,4,47] and cellular neurophysiology [48,49]. O. vulgaris has also served as an attractive model for neuroendocrine studies in invertebrates [5,50].
Recently, Octopus bimaculoides (California Two-spot Octopus) has emerged as a model system for cephalopod biology. The large size of O. bimaculoides eggs grants unique access to early embryonic stages, making this species a prime candidate for future genetic and developmental studies. The hardiness, ready availability in the United States and easy husbandry of adult O. bimaculoides  add to the appeal of this model species.
The deadly venom of blue-ringed octopus Hapalochlaena maculosa makes this species of interest for study of the evolution and regulation of toxicity within octopods .
Comparative studies of these octopus species would illuminate the bases of both their shared characteristics as well as those of their divergent features. Additionally, these species have essentially non-overlapping geographic distributions, providing animal accessibility to cephalopod researchers globally.
Within the decapodiforms, Sepia and Loligo are the most studied genera. Historically, Sepia officinalis has been a key cephalopod for neurobiological research, and is a critical species in global fisheries. S. officinalis possesses a complex chromatophore network for countershading, camouflage and communication [3,52,53]. Its internal calcified shell supplies buoyancy and the effect of global climate changes on this structure has become a focus of recent study [54,55]. S. officinalis is emerging as a particularly versatile model organism in eco-evo-devo studies . As a practical matter, S. officinalis eggs are voluminous, and easily collected, maintained and reared in the laboratory . The morphological events in S. officinalis embryogenesis are well described in the literature [58-61].
Loligo, and particularly its giant fiber system, has served as the fundamental basis for our understanding of nerve impulse conduction. The giant synapse system has recently been employed as a biomedical model of neurological disease . Loligo is one of the most important groups for cephalopod fisheries in the North Atlantic . Loligo pealeii is the premier experimental species of the loliginids, with not only an extensive publication base , but also annual availability at the Marine Biological Laboratory (Woods Hole, MA).
Euprymna scolopes is a unique cephalopod model organism because of its well-described symbiotic relationship with the luminescent bacterium Vibrio fischeri. This important biomedical model has been employed to study the mechanisms of host colonization and symbiont specificity, host/microbe cell-cell signaling, and innate immunity [64-67]. Euprymna scolopes’ short life cycle and small egg size also make it an attractive choice for developmental studies in culture [68,69]. In 2005, the V. fischeri genome was sequenced ; having access to the host genome would allow this field to advance rapidly.
Pygmy squids (Idiosepius) have one of the smallest genomes among cephalopods (2.1 Gb), making them strong candidates for assembly and annotation . Their small body size and exceptionally short life cycle also distinguish these cephalopods as possible model organisms .
The giant squid Architeuthis dux serves to represent deep-sea cephalopods. Little is known about the species of Architeuthis. Architeuthis is globally distributed and a recent analysis of the complete mitogenomes of multiple giant squid worldwide showed no detectable phylogenetic structure on the mitochondrial level and an exceptionally low level of nucleotide diversity, suggesting that there is only one global species of giant squid . A nuclear reference genome for Architeuthis would clarify the population genetics of this species and provide critical information for comparative studies across cephalopods.
Nautilus, the cephalopod “living fossil”, is a representative of a phylogenetically unique branch of the cephalopods, the nautiloids. Nautilus possesses many presumably ancestral anatomical features not shared with other cephalopods, including pinhole eyes, rhinophores for odor detection, an external shell, and numerous tentacles, all without suckers . Comparative genomic studies employing Nautilus would highlight the genetic bases of these divergent features.