CAREER: The genetic and developmental basis of body size evolution in nematodes

University Of Oklahoma Norman Campus, Norman OK

Investigators

Abstract

The diversity among animal body sizes (from at least ants to elephants) is immense and demands explanation. Yet, the genetic and developmental changes that cause body size evolution remain unknown. The proposed work aims to address this problem by harnessing both long-established and cutting-edge genetic techniques in closely-related roundworm species with drastically different body sizes to identify the causes of body size variation. This work is important because we know larger roundworm species have larger cells than those of smaller species, and when the processes regulating cell size go awry, diseases such as cancer emerge. This work then has the potential to discover novel genes that control cell size and thus potential novel targets for cancer therapeutics. Beyond this, the research work described above will be integrated with multiple, established educational initiatives in the state of Oklahoma including: 1) The University of Oklahoma’s four-year undergraduate research experience program; 2) A multi-year summer research program for undergraduates; 3) A research experience for high school students summer program; and 4) A graduate-student led summer coding workshop. Additionally, an undergraduate developmental biology laboratory course will be developed where students will participate in the original research activities described above. The proposed work not only aims to make significant advances in understanding the evolution of body size and the genes underlying cell size variation, but this work also aims to connect multiple educational efforts with these research efforts to simultaneously advance both scientific knowledge and societal good. Understanding how developmental systems evolve to promote phenotypic diversity is a fundamental goal of biology. These systems include and regulate the morphogenetic fields, signaling factors, and differentiation decisions essential for the construction and ultimate form of a multicellular organism. Despite this, while gene regulatory networks have been painstakingly described in a handful of model systems, network architecture change is rarely connected to morphological divergence among species. How does genetic variation change developmental processes to cause divergent phenotypes? Over forty years of C. elegans genetics has revealed the developmental details of a canonical TGF-β signaling network that regulates body size in this species. C. inopinata is the sister species of C. elegans, and it is nearly twice as long in size as its highly-studied close relative. Here, the vast background knowledge of a long-standing model system will be integrated with a comparative approach to understand how network modification causes phenotypic divergence. This work will include: 1) The perturbation of TGF-β pathway activity in two species to determine how ancestral body size genes evolve to promote cell size divergence; 2) The generation and mapping of large-effect body size mutations in C. inopinata to discover novel genes driving cell size regulation; and 3) The characterization of tissue-specific cell size variation in mutants across development in two species. Not only will this work map genotypes to organismal phenotypes such as body size, but it will also show how genotypes influence cellular phenotypes to cause the emergence of such organismal phenotypes. This project is jointly funded by the BIO-IOS-Developmental Systems Program and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.