Molecular Correlates of Programmed Genome Rearrangements in Lamprey

The lamprey undergoes programmed genome rearrangements (PGRs) during early embryogenesis that result in the deletion of ~0.5 gb of germline DNA from somatic cell lineages. Previous analyses of the deleted portion have shown that hundreds of genes are removed from somatic tissue but maintained in germline, and that deleted genes have a strong potential for antagonistic pleiotropic interactions if misexpressed in somatic tissues. Given that rearrangements are highly reproducible, presumably act as a large-scale gene regulatory mechanism, we hypothesize that PGR may be functionally related to (or interact with) other global gene regulatory mechanisms.

Understanding the relationship of these molecular mechanisms could provide insight into a unique form of vertebrate genome biology (PGR), and allow for the identification of similar pathways in humans. Mechanisms such as histone modification and DNA methylation have been shown to control gene expression during development, and are likely contributors to PGR regulation. Indeed, quantification of global 5-methylcytosine content across early development reveals unique changes in DNA methylation that are temporally coordinated with PGR. Similarly, micro RNAs (miRNAs) are known to be important post-transcriptional factors for gene silencing. In silico analysis of germline and somatic genomes reveals a marked difference in the miRNA, suggesting an interaction between miRNA and PGR regulatory mechanisms.

These studies reveal interactions between PGR and other global regulatory pathways known to operate in other vertebrates. Future experiments will provide a deeper understanding of this unique form of genome control, and potentially provide insight into similar pathways operating in the human genome.