A Deep Evolutionary Perspective on Vertebrate Genome Biology
The lamprey genome provides unique insights into both the deep evolutionary history of vertebrate genomes and the maintenance of genome structure/integrity over development. The lamprey lineage diverged from all other vertebrates approximately 500 million years ago. As such, comparisons between lamprey and other vertebrates permit reconstruction of ancient duplication and rearrangement events that defined the fundamental architecture and gene content of all extant vertebrate genomes. Lamprey also undergoes programmatic changes genome structure that result in the physical elimination of ~20% of its genomic DNA (~0.5Gb from a ~2 Gb genome) from all somatic cell lineages during early embryonic development. Here, we outline recent progress in assembly and analysis of the lamprey germline genome, and progress in the development of methods for characterizing the cellular events that mediate DNA elimination. We have integrated information from several sampling approaches and sequencing technologies to achieve a highly contiguous assembly of lamprey genome (including: Illumina fragments/mate pairs, 20X coverage in Pacific Biosciences reads, dense meiotic maps and optical mapping data). This genome assembly has dramatically improved our ability to dissect the molecular basis and genetic outcomes of programmed genome rearrangements (PGRs), and has improved our understanding of the tempo and mode of large-scale duplications and translocations within the ancestral vertebrate lineage. Analysis of the germline genome identifies several genes that are expressed in germline but physically eliminated from all somatic tissues. These eliminated genes correspond to several known oncogenes and appear to identify several other novel oncogene candidates. Complementing this assembly, the development of approaches to in situ analysis of 3D preserved cells has revealed that PGR unfolds through a series of dramatic cellular events that involve the programmatic alteration of several fundamental mechanisms of genome maintenance, including: alignment of chromosomes at metaphase, chromatid cohesion, separation and segregation, and nuclear envelope formation.