Replication asynchrony during mitotic S-phase is a hallmark of monoallelic gene expression. In addition to the well-known examples of monoallelic expression including genomic imprinting and X chromosome inactivation, 5-10% of genes undergo random monoallelic expression in humans (Gimelbrant et al. 2005). In addition to asynchronous replication monoallelicly expressed genes undergo increased amounts of chromatin interactions (Ryba, Hiratani et al. 2010). Here we addressed the question of how replication asynchrony evolved in relation to interchromosomal interaction and monoallelic expression in mammals for a small number of genes. Our findings in monotremes confirm that asynchronously replication is conserved in platypus orthologs of genes imprinted in therian mammals (Kitsberg, Selig et al. 1993; Dünzinger, Nanda et al. 2005), this is despite the fact that to date there is no evidence for genomic imprinting in monotremes. Furthermore sequential FISH on the same set of nuclei showed for the first time a high level of conservation of the order in which a set of genes are replicated in mammals and birds. We also confirmed for the first time that the interchromosomal interaction between Igf2-Wsb1 described in mouse (Ling, Li et al. 2006) is conserved in platypus and chicken. We also investigated platypus gene expression using RNA-FISH and deep sequencing. Surprisingly we found some evidence for monoallelic expression for genes in platypus that are imprinted in therian mammals which would explain why these genes are still featuring asynchronous replication