Yiqing Guo, PhD, postdoctoral fellow, and mentor Ronald Ellis, PhD, associate professor, Department of Molecular Biology, UMDNJ-School of Osteopathic Medicine
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ow are novel traits created during evolution? In the nematode genus Caenorhabditis, hermaphroditism evolved independently several times. We are studying how genes that control this trait evolved. Our results show that hermaphrodites were created from female ancestors by modification of the germ-line sex-determination pathway. Surprisingly, in two different hermaphroditic species, new F-box proteins evolved to control the activity of the tra-2 gene, allowing limited spermatogenesis in an otherwise female body.
Sex-determination mechanisms vary dramatically between different phyla. For example, in mammals the SRY gene on the Y chromosome determines male development, whereas in fruit flies and nematodes the ratio of X chromosomes to autosomes determines sex. Because of these large differences between phyla, we need to study closely related species to learn how sexual traits change.
Thus, we are studying the evolution of nematodes in the genus Caenorhabditis. All species in this genus share a similar body structure, and most of them produce males and females. However, C. elegans and C. briggsae usually reproduce as self-fertile hermaphrodites (Fig. 1). Although males are less common in nature, genetic tests show that they remain important. In C. elegans, the sex-determination pathway is well understood at the molecular level, and the core of this pathway is conserved in C. briggsae. However, C. briggsae is more closely related to male/female species like C. remanei than it is to C. elegans (Fig. 2A). This result implies that C. elegans and C. briggsae evolved hermaphroditic reproduction independently.
To identify genes that control hermaphrodite development in C. briggsae, we screened for mutations that transform XX animals into females. We isolated 1 dominant and 14 recessive mutations, which define at least six genes. Four of the recessive mutations (v35, v49, v51, v83) affect XX spermatogenesis but have no effect on XO males, which indicates that they specifically regulate hermaphrodite development. These mutations all fail to complement each other, so they define a single gene. Since these mutations create spermless hermaphrodites, we named the gene they affect she-1.
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Figure 1: Schematic of Hermaphrodite of Caenorhabditis elegans. (WormAtlas) |
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| Figure 2: Sex-determination Pathway and Phylogeny of the genus Caenorhabditis. |
To learn where she-1 functions in the sex-determination pathway (Fig. 2B), we examined the interaction of she-1 with other mutations. The she-1 fem-3 double mutants develop as female, whereas she-1 fem-3 tra-2 triple mutants become self-fertile hermaphrodites. Thus, we believe that she-1 functions upstream of the tra-2 gene. We propose that she-1 temporarily suppresses the function of tra-2 to allow spermatogenesis in hermaphrodites. Additional data suggest that tra-2 regulates the fem proteins and the transcription factor tra-1.
To learn how she-1 works, we cloned the gene using single nucleotide polymorphism (SNP) mapping, and found that she-1 encodes a novel F-box protein, which may act as a connector to target other proteins’ ubiquitinylation and degradation. The she-1 gene was the first to be cloned by SNP mapping in C. briggsae.
In C. elegans, the Schedl group showed that fog-2, which also encodes an F-box protein, uses a novel mechanism to repress tra-2 message RNA translation. Our molecular phylogeny shows that she-1 is not related to fog-2. Instead, she-1 is part of a family of four C. briggsae F-box genes, located in the same region of chromosome IV. Thus, she-1 appears to have evolved recently by gene duplication.
Based on these findings, we propose that C. briggsae evolved from a female ancestor by recruiting a novel F-box protein to repress the activity of tra-2, allowing spermatogenesis in a female body. Our results show that gene duplications can create novel traits and suggest that F-box genes can rapidly duplicate and diverge in function.
Yiqing Guo earned his PhD in 2004 from the College of Life Sciences, Wuhan University, China. He has been a postdoctoral research fellow in the laboratory of Ron Ellis at UMDNJ’s School of Osteopathic Medicine since 2005.
