Petromyzon marinus

The sea lamprey is a member of an ancient lineage that diverged from the vertebrate stem approximately 550 million years ago (MYA). By virtue of this deep evolutionary perspective, lamprey has served as a critical model for understanding the evolution of several conserved and derived features that are relevant to broad fields of biology and biomedicine. Studies have used lampreys to provide perspective on the evolution of developmental pathways that define vertebrate embryogenesis, vertebrate nervous and neuroendocrine systems, genome structure, immunity, clotting and others. These studies reveal aspects of vertebrate biology that have been conserved over deep evolutionary time and reveal evolutionary modifications that gave rise to novel features that emerged within the jawed vertebrate lineage (gnathostomes). Lampreys also possess several features that are not observed in gnathostomes, which could represent either aspects of ancestral vertebrate biology that have not been conserved in the gnathostomes or features that arose since the divergence of the ancestral lineages that gave rise to lampreys and gnathostomes. These include the ability to achieve full functional recovery after complete spinal cord transection, deployment of evolutionarily independent yet functionally equivalent adaptive immune receptors, and the physical restructuring of the genome during development known as programmed genome rearrangement (PGR).

Programmed genome rearrangement results in the physical elimination of ~0.5 Gb of DNA from it’s ~2.3 Gb genome. The elimination events that mediate PGR are initiated at the 7th embryonic cell division and are essentially complete by 3 days post fertilization. As a result, lampreys are effectively chimeric, with germ cells possessing a full complement of genes and all other cell types possessing a smaller, reproducible, fraction of the germline genome. Previous analyses support the idea that the somatic genome lacks several genes that contribute to the development and maintenance of germ cells but are potentially deleterious if misexpressed in somatic lineages. However, our understanding of the mechanisms and consequences of PGR remains incomplete, as only a fraction of the germline genome has been sequenced to date.

In contrast to the germline genome, the somatically retained portions of the genome are relatively well characterized. Because PGR was not known to occur in lampreys prior to 2009, sequencing efforts focused on somatic tissues from which DNA or intact nuclei could be readily obtained (e.g. blood and liver). Sequencing of the sea lamprey somatic genome followed an approach that had proven successful for other vertebrate genomes prior to the advent of next generation sequencing technologies (Sanger sequencing of clone ends, fosmid ends and BAC ends). Due to the abundance of highly-identical interspersed repetitive elements and moderately high levels of polymorphism (approaching 1%), assembly of the somatic genome resulted in a consensus sequence that was substantially more fragmentary than other Sanger-based vertebrate assemblies. Nonetheless, this initial assembly yielded significant improvements in our understanding of the evolution of vertebrate genomes and fundamental aspects of vertebrate neurobiology, immunity and development.

This assembly represents the first assembly of the sea lamprey germline genome. Through extensive optimization of assembly pipelines, we identified a computational solution that allowed us to generate an assembly from next-generation sequence data (Illumina and Pacific Biosciences reads) that surpasses the existing Sanger-based somatic assembly. Analysis of the resulting assembly has revealed several hundred genes that are eliminated from somatic tissues by PGR and sheds new light on the evolution of genes and functional elements in the wake of ancient large-scale duplication events.

Dr. Robb Krumlauf's Group, here at the Stowers Institute for Medical Research, is studying the Hox gene clusters in the sea lamprey and comparing their organisation with those of jawed vertebrates. The Hox family of transcription factors are encoded by genes that reside in genomic clusters and play key anterior-posterior patterning roles in multiple tissues during embryonic development. Hox genes exhibit segmental domains of activity in the developing head and neck that are remarkably similar between different vertebrate species. A remarkable feature of Hox gene expression during embryogenesis is that the order and timing of Hox gene expression along the embryonic anterior-posterior axis correlate with the relative positions of those genes along the Hox cluster. It is widely held that the emergence of gene regulatory networks governing Hox-dependent patterning of the embryonic brain and pharynx were fundamentally important events during the evolution of the complex vertebrate head. Thus, it is important to understand when and how these molecular cascades evolved in early vertebrates. As one of the only living jawless vertebrates, the sea lamprey is a crucial model organism for such endeavours, and research into the sea lamprey Hox genes is illuminating these important questions.

EMBARGO ON DATA USE: We are delighted to make lamprey genomes available to the broader community. We encourage others to use these data, but in doing so we also expect that they will respect our right to first presentation (including journal publications, pre-prints such as in bioRxiv, public conference talks, and press releases) of a genome-wide analysis of these assemblies. This includes the use of genome-wide data for phylogenetic and evolutionary analysis, on behalf of ourselves as data producers, the sample providers and collaborators. Therefore, please respect the embargo on the presentation of analyses using pre-publication data that we release via this website and relevant archives. Similar fair use statements apply to other assemblies such as those released by the Sanger Institute and the VGP.

Exceptions to the policy are for analyses of either a single locus, or a single gene family, or a maximum of 5 gene loci across multiple species, or for use as a reference for mapping reads from independent studies. Individual genomes and datasets will be considered released from this embargo when they are expressly published, and the relevant reference(s) will be added to this website at that time. For any queries about using the data, referencing/publishing analyses based on pre-publication data or interest in contributing to genome-scale analyses please contact jjsmit3@uky.edu. Use of data for sea lamprey are also covered under the VGP data use policies

The following assemblies are currently under embargo: Petromyzon marinus (kPetMar1), Entosphenus tridentatus (ETR male, ETR female), Lampetra richardsoni (LPT). gPmar100 was published in Nature Genetics (2018)

Funding Statement: Funding from several sources contributed to the assembly and annotation of the sea lamprey genome assembly, including funding from the Great Lakes Fisheries Commission to Jeramiah Smith and Erich Jarvis; funding from the NSF under grant number MCB-1818012 to J Smith, and funding from the NIH under grant number R35GM130349 to J Smith. The support and resources from the Center for High Performance Computing at the University of Utah are gratefully acknowledged. The computational resources used were partially funded by the NIH Shared Instrumentation Grant 1S10OD021644-01A1.