The Sins of Our Kin: From Genomic Imprinting to Ancient Signaling Systems

Abstract

The bond between parents and their offspring is often regarded as something loving and supportive. But, this bond is more of a battle. Genomic imprinting is the result of the evolutionary struggle between mothers and fathers for reproductive success. The first part of the thesis describes the 3’- untranslated region (3’-UTR) of the insulin-like growth factor type 1 receptor (IGF1R) as an ancient long noncoding RNA. The 3’-UTR of the mouse Igf1r mRNA is targeted by miR-675-3p derived from the imprinted H19 long noncoding RNA. We undertook a comparative analysis of vertebrate IGF1R 3’-UTRs to determine the evolutionary history of miR-675 target sequences and to identify conserved features that are likely to be involved in post-transcriptional regulation of IGF1R translation. The conserved structures we identify emphasize the central importance of IGF signaling pathways in the mediation of intragenomic conflicts over embryonic growth. The second part is aimed at investigating the Retrotransposon Gag-like 1 (RTL1) and the molecular evolution of self-targeting imprinted microRNAs. Transcription of the sense strand of the RTL1 gene produces a protein-coding mRNA that is targeted for degradation by microRNAs transcribed from the antisense strand of the protein-coding sequence. The sense and antisense transcripts are oppositely imprinted. We present an evolutionary model for the establishment of a new self- targeting microRNA derived from within a tandem repeat that inhibits production of RTL1 protein when maternally-derived in heterozygotes but not when paternally- derived. Lastly, oxytocin has commonly been viewed as a molecule that can melt away malevolence and increase bonding. Its effects, however, are involved in the process of smooth muscle contraction. Oxytocin is a member of a nonapeptide family constituting an evolutionarily conserved signaling system found in vertebrates and invertebrates. We postulate that there is an evolutionary connection among the vari- ous functions attributed to these peptides. We believe that the acute anorexic effects of oxytocin, and its orthologs, released during egg-laying inhibits the consumption of a female’s own eggs and that the first evolutionary use of oxytocin peptides in social bonding was in the promotion of nurturing feelings towards clutches of fertilized eggs.