The advent of genome sequencing restored evolutionary studies to a central place in biomedical research, since they are essential for interpretting how information about regulatory pathways in model organisms might apply to humans. One of the big questions in the field is how these regulatory pathways evolve. Three factors make nematodes an excellent model for studying evolutionary processes. First, C. elegans is a major focus of study about reproductive biology, cell death, micro-RNAs, aging, and other subjects of interest to physicians. Second, the genomic and functional tools available for working with these animals are outstanding. Third, excellent traits are available for study. For example, hermaphrodite development evolved independently in the nematodes C. elegans and C. briggsae. This proposal describes experiments that use genetic and molecular techniques to learn how hermaphroditic development evolved in C. briggsae. Since hermaphrodite nematodes modulate the sex-determination pathway to allow XX animals to make sperm, this trait is ideal for learning how regulatory pathways change during evolution. So far, we have identified and cloned glf-1, which causes XX animals to develop as hermaphrodites, and glf-2, which acts downstream of glf-1. These genes are novel to C. briggsae, and critical to learning how hermaphrodite development originated. This project has three specific aims. The first is to screen for proteins that interact with GLF-1. Since GLF-1 is a member of a new class F-box proteins, its binding partners are the key to understanding how it controls development.
The second aim i s to clone and characterize glf-2, a new sex-determination gene that acts downstream of glf-1 to promote spermatogenesis.
The third aim i nvolves the use of enhancer and suppressor screens to identify additional genes that act in this pathway, and to characterize these genes. These genes would be candidates for future cloning and molecular analyses. Many genes cooperate to regulate how humans develop and fight disease. Much of the basic research funded by the NIH focuses on how these genes work by studying them in simple creatures. This project will elucidate how the functions of genes change during evolution, which could help scientists choose which creatures to study, and avoid mistaken inferences about their medical significance.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Eckstrand, Irene A
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University of Medicine & Dentistry of NJ
Schools of Osteopathic Medicine
United States
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Chen, Xiangmei; Shen, Yongquan; Ellis, Ronald E (2014) Dependence of the sperm/oocyte decision on the nucleosome remodeling factor complex was acquired during recent Caenorhabditis briggsae evolution. Mol Biol Evol 31:2573-85
Wei, Qing; Shen, Yongquan; Chen, Xiangmei et al. (2014) Rapid creation of forward-genetics tools for C. briggsae using TALENs: lessons for nonmodel organisms. Mol Biol Evol 31:468-73
Chu, Hsueh-Ping; Liao, Yi; Novak, James S et al. (2014) Germline quality control: eEF2K stands guard to eliminate defective oocytes. Dev Cell 28:561-572
Ellis, Ronald E; Lin, Shin-Yi (2014) The evolutionary origins and consequences of self-fertility in nematodes. F1000Prime Rep 6:62
Guo, Yiqing; Chen, Xiangmei; Ellis, Ronald E (2013) Evolutionary change within a bipotential switch shaped the sperm/oocyte decision in hermaphroditic nematodes. PLoS Genet 9:e1003850
Baldi, Christopher; Viviano, Jeffrey; Ellis, Ronald E (2011) A bias caused by ectopic development produces sexually dimorphic sperm in nematodes. Curr Biol 21:1416-20
Ellis, Ronald E; Wei, Qing (2010) Somatic signals counteract reproductive aging in females. Genome Biol 11:142
Nakano, Shunji; Ellis, Ronald E; Horvitz, H Robert (2010) Otx-dependent expression of proneural bHLH genes establishes a neuronal bilateral asymmetry in C. elegans. Development 137:4017-27