Root, Z. D. | bioRxiv Science

bioRxiv2026

Functional Analyses of Histone Methyltransferases in Sea Lamprey Embryos Undergoing Programmed DNA Elimination

During early embryogenesis, the sea lamprey (Petromyzon marinus) undergoes a dramatic form of genome reprogramming wherein specific chromosomes are selectively eliminated from somatic progenitor cells. These programmatic elimination events effectively silence all genes on these chromosomes in all somatic cells. Previous studies in lamprey and other eliminating species have shown that epigenetic silencing marks are enriched on germline-specific chromosomes during programmed elimination. These silencing marks include the histone marks H3K9me3 and H4K20me3, which are respectively deposited by KMT1A/SUV39 and KMT5/SUV420 methyltransferases. To test whether lamprey homologs of these methyltransferases contribute to deposition of silencing marks on eliminated (micronucleated) chromatin and whether these marks contribute to the highly coordinated process of DNA elimination in sea lamprey, we used Cas9 gene editing, lightsheet imaging and RNA sequencing to investigate their potential roles in DNA elimination and more generally during early development. Analysis of knockout embryos for four histone methyltransferases show that these genes contribute to the deposition of repressive histone marks on elimination micronuclei, but are not essential for programmed DNA elimination per se. Analysis of later embryogenic stages suggests that these marks may contribute to interim silencing of germline-specific chromosomes, and reveals major impacts on post-blastula survival and development.

evolutionary biology↗

bioRxiv2020

Lamprey Lecticans Link New Vertebrate Genes to the Origin and Elaboration of Vertebrate Tissues

The evolution of vertebrates from an invertebrate chordate ancestor involved the evolution of new organs, tissues, and cell types. It was also marked by the origin and duplication of new gene families. If, and how, these morphological and genetic innovations are related is an unresolved question in vertebrate evolution. Hyaluronan is an extracellular matrix (ECM) polysaccharide important for water homeostasis and tissue structure. Vertebrates possess a novel family of hyaluronan binding proteins called Lecticans, and studies in jawed vertebrates (gnathostomes) have shown they function in many of the cells and tissues that are unique to vertebrates. This raises the possibility that the origin and/or expansion of this gene family helped drive the evolution of these vertebrate novelties. In order to better understand the evolution of the lectican gene family, and its role in the evolution of vertebrate morphological novelties, we investigated the phylogeny, genomic arrangement, and expression patterns of all lecticans in the sea lamprey (Petromyzon marinus), a jawless vertebrate. Though both P. marinus and gnathostomes have four lecticans, our phylogenetic and syntenic analyses suggest lamprey lecticans are the result of one or more cyclostome-specific duplications. Despite the independent expansion of the lamprey and gnathostome lectican families, we find highly conserved expression of lecticans in vertebrate-specific and mesenchyme-derived tissues. We also find that, unlike gnathostomes, lamprey expresses its lectican paralogs in distinct subpopulations of head skeleton precursors, potentially reflecting an ancestral diversity of skeletal tissue types. Together, these observations suggest that the ancestral pre-duplication lectican had a complex expression pattern, functioned to support mesenchymal histology, and likely played a role in the evolution of vertebrate-specific cell and tissue types.

evolutionary biology↗