Genomic Annotation and the Post-Reproductive Shift of Caenorhabditis briggsae and Comparative Analysis within the Caenorhabditis Genus

Abstract

The comparative study of species is the method that allows biologists to find shared traits and functions. Darwin and Wallace realized that the same method could ultimately be used to determine shared origins, bringing forth the field of evolutionary biology. Modern technologies have expanded how we can compare species, on the levels that are foundational to bringing about those phenotypes: the genome, transcriptome and proteome. The nematode Caenorhabditis elegans is one of the most well-studied model organisms, with a genome that is extensively sequenced and annotated. C. briggsae is a satellite model to C. elegans and offers a closely-related comparison point which allows for reliable comparative analyses among nematodes as well as with more complex organisms. My Ph.D. work has contributed to improving the genome annotation of C. briggsae, and provides the first adult longitudinal transcriptome analysis for the species. Through my work I have uncovered that, as the organism ages and becomes post-reproductive, C. briggsae undergoes a transcriptomic post-reproductive shift which affects many of its biological processes including reproduction, the matrisome, function and development of muscles, DNA repair, immune response and stress response. In comparative analysis I have shown that the shift is largely absent in C. elegans, highlighting the importance of including multiple closely related species in comparative transcriptome analyses. Discovery of the C. briggsae post-reproductive shift prompted further investigation of two gene families: the caenacins, involved in innate immunity, and the hsp16 and hsp70 family genes, involved in the response to heat stress. With regards to the former, I determined the involvement of several caenacins in survival and contributed to elucidating the evolutionary context of caenacins and the role they play in immune-protection against fungal pathogens. Secondly, I determined the phylogenetic relationships of hsp16 and hsp70 genes among nematodes. I have shown hsp16s to display a high degree of genomic clustering along with expression patterns that suggest recent duplications, and shared regulation between gene pairs. This fundamental research on the genomic and transcriptomic differences between C. briggsae, C. elegans and other nematodes will provide a knowledge basis for future research. Overall, my Ph.D. research has provided new insights into the effects that entering a post-reproductive state can have on the physiological processes of nematodes.