Investigating the evolution of replication timing and monoallelic expression in mammals and birds

Monoallelic expression and replication timing are closely linked fundamental aspects of genome biology, yet their evolutionary trajectory has not been investigated in much detail. The monoallelic expression status of imprinted genes observed in therian species has previously not been found in the earlier-diverged monotreme mammals, or in birds, when measured using molecular techniques. Furthermore, the observation that eutherian imprinted and X-borne genes asynchronously replicate was traditionally thought to be linked to the dissimilar epigenetic states that existed at each allele controlling monoallelic expression. In this study, we use a combination of cytogenetic and molecular techniques to assess the replication status of sex chromosome genes in the platypus and chicken, as well as the replication status and expression pattern of platypus imprinted orthologs. We find that asynchronous replication does occur at specific sex chromosome loci in platypus and chicken, although in chicken the amount of asynchronous replication changes over development. Furthermore, differential chromatin compaction is observed in platypus sex chromosomes, a characteristic observed in therian X-inactivation, suggesting that both asynchronous replication and chromatin compaction are features characteristic of amniote sex chromosomes. Asynchronous replication and monoallelic expression is observed at platypus imprinted orthologs, indicating that a ‘pre-imprinted’ status is observed at these genes in non-therian amniote species. These results show that monoallelic expression predates imprinting at these loci, suggesting that the partial monoallelic expression observed in monotreme mammals has evolved in therian mammals to become parentally-inherited imprinted expression.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Molecular and Biomedical Science, 2015