Characterization of Somatically-Eliminated Genes in the Sea Lamprey

The sea lamprey (Petromyzon marinus) is one of few vertebrates known to undergo broad-scale programmed genome rearrangement (PGR) events, which facilitate the deletion of approximately 0.5 Gb (~20%) of DNA from somatic cell lineages. Sequencing of the sea lamprey genome has revealed that regions excised during PGR include hundreds of genes and other single-copy DNAs, many of which have human homologs that contribute to germline biology or pluripotency. Yet there are still many somatically-eliminated genes that have yet to be identified, or whose functions remain unknown. To further characterize the subpopulation of genes eliminated during PGR, we generated RNAseq data from meiotic germline and embryos sampled across early embryonic development.

Analysis of RNAseq and genomic datasets identified a large number of candidate genes. Validation studies targeted a subset of these and identified 49 genes that could be definitively classified as somatically-eliminated. Functional information for homologs of these genes indicates that many have germline-specific functions or roles in maintenance of undifferentiated cell fates. Many are also known to contribute to cancers when misexpressed in somatic cell lineages. While other genes are not currently annotated as such, their elimination in lamprey suggests they may have similar functions or the potential to engage in other pleiotropic interactions (e.g. aging or other genomic disorders). Moreover, RNAseq data show that eliminated genes are expressed throughout embryogenesis. These findings and broaden our understanding of the functional significance of genes that are targeted for programmed elimination, both in developing germ cells and the adult germline.