Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution

Abstract

Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.

Figure 1

An abridged phylogeny of the vertebrates. Shown is the timing of major radiation events within the vertebrate lineage. Extinct lineages and some extant lineages (for example, coelacanths, lungfish and hagfish) have been omitted for simplicity. Here, reptile is synonymous with sauropsid, ray-finned fish is synonymous with actinopterygian, and osteichthyan is synonymous with euteleostome. CZ, Cenozoic; MYA, million years ago.

Figure 2

Genome-wide deviation of lamprey coding sequence properties from patterns observed in other vertebrate and invertebrate genomes. (a) Codon usage bias. Correspondence analysis (CA) on relative synonymous codon usage (RSCU) values was performed using the nucleotide sequences of all predicted genes concatenated for individual species. (b) Amino-acid composition. Red, lamprey; gray, invertebrates; green, jawed vertebrates.

Figure 3

Conserved synteny and duplication in the lamprey and gnathostome (chicken) genomes. (a–d) The locations of presumptive lamprey-chicken orthologs (including duplicates) are plotted relative to their physical positions on chromosomes and scaffolds and are connected by colored lines. (a,b) Pairs of chicken chromosomes that correspond to a series of lamprey scaffolds. (a) Ten lamprey loci are present as duplicate copies in the chicken genome, and 59 are present as single copies. (b) Twelve lamprey loci are present as duplicate copies in the chicken genome, and 54 are present as single copies. (c,d) Pairs of lamprey scaffolds that correspond to individual chicken chromosomes. (c) Three chicken loci are present as duplicate copies on syntenic lamprey scaffolds. (d) Two chicken loci are present as duplicate copies on syntenic lamprey scaffolds. Asterisks indicate duplicates.

Figure 4

The effect of genome duplication and independent paralog loss on the evolution of lamprey-gnathostome conserved syntenic regions. (a) Conserved synteny among the GnRH2, GnRH3 and (previously proposed) GnRH4 genes in lamprey, chicken and humans, including the medaka region for GnRH3, which is absent in tetrapods. The orientation of each chromosome (chr.) and scaffold (scf.) is indicated with line arrows. A pointed box represents the orientation of each gene. Open rectangles with red X’s indicate lost GnRH loci. The presumptive ancestral state of the gene region is shown at the bottom. (b) Assembled lamprey Hox scaffolds and patterns of conserved synteny relative to human Hox clusters (human Hox clusters rather than chicken are used because all four human Hox syntenic regions are integrated into the human genome assembly). Three additional conserved syntenic genes, located adjacent to the PM2Hox cluster, are omitted owing to space limitations (retinoic acid receptor (RAR), heterogeneous nuclear ribonucleoprotein (HNRNP) and thyroid hormone receptor (THR)). Symbols indicate representative family members of lamprey-gnathostome homology groups.

Figure 5

Enrichment of gene ontologies among vertebrate-specific gene families. Horizontal bars show the frequencies of ontology classes among vertebrate-specific gene families and in the entire set of lamprey gene models. Data are shown for all ontologies that are over-represented with P < 0.005 (Fisher’s exact test). Most over-represented ontologies are related to neural development and neurohormone signaling.

Figure 6

Absence of sequence conservation for a limb Shh enhancer in lamprey. Comparison of an intronic region in the Lmbr1 gene, focusing on the intron containing the Shh cis-regulatory element (ShARE, also known as MFCS1)^,. Note that two genomic regions were identified in the lamprey harboring potential Lmbr1 orthologs. The lengths of this intron for individual species are listed on the right. ND, not determined.