The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution

Abstract

The sea lamprey (Petromyzon marinus) serves as a comparative model for reconstructing vertebrate evolution. To enable more informed analyses, we developed a new assembly of the lamprey germline genome that integrates several complementary datasets. Analysis of this highly contiguous (chromosome-scale) assembly reveals that both chromosomal and whole-genome duplications have played significant roles in the evolution of ancestral vertebrate and lamprey genomes, including chromosomes that carry the six lamprey HOX clusters. The assembly also contains several hundred genes that are reproducibly eliminated from somatic cells during early development in lamprey. Comparative analyses show that gnathostome (mouse) homologs of these genes are frequently marked by Polycomb Repressive Complexes (PRCs) in embryonic stem cells, suggesting overlaps in the regulatory logic of somatic DNA elimination and repressive/bivalent states that are regulated by early embryonic PRCs. This new assembly will enhance diverse studies that are informed by lampreys’ unique biology and evolutionary/comparative perspective.

A genome-wide assessment of the ancestral neural crest gene regulatory network

“…48% of these overlap with predicted lncRNA from adult sea lamprey brain, heart, kidney, and gonad RNA-seq datasets 19 , while 70% were associated with ATAC-seq positive regions. The gnathostome HoxA locus is known to harbour lncRNAs, including HOTAIRM1 47 and HOTTIP 48 , both of which have been shown to modulate gene expression in cis.…”

“…67,736 of the transcripts did not overlap with any annotated genes and thus represent candidate novel transcripts or transcribed transposable elements. The latter are present in large numbers in the lamprey genome but were not integrated in the current conservative gene model annotation that excluded repetitive elements 19 . Principal component analysis (PCA) of dorsal neural tube count data showed clear separation along principal component 1 (PC1), which accounted for 90% of the variance, reflecting the developmental stage at which the tissue was sampled (Fig.…”

“…First, we assessed the dynamics of signalling molecules and transcription factors known to be expressed during neural crest specification making use of the germline genome annotation that used multispecies BLAST alignments to assign lamprey gene models to likely vertebrate homologues 19 . As expected, several bona fide neural crest markers were enriched at T21 when compared to T18 (Fig.…”

“…Whereas the GRN of gnathostome neural crest has been greatly expanded, progress in reconstructing the neural crest GRN of jawless vertebrates has been limited due to incomplete genomic information. Recently, a germline genome assembly for the sea lamprey, that unlike previous assemblies 16 is not affected by DNA-elimination 17,18 and uses an integrated scaffolding approach to increase contiguity to near chromosome-scale resolution 19 , has made it possible to interrogate the regulatory genome of this basal vertebrate. Using this assembly, it is now possible to integrate gene expression data and cis-regulatory analyses on a genome-wide scale with increased confidence.…”

“…2a), representing the migratory and post-migratory neural crest. ATAC-seq datasets were mapped to and analysed within the context of the sea lamprey germline genome assembly 19 . Mapped ATAC-seq biological replicate datasets were highly correlated ( Supplementary Fig.…”