Sex‐determination gene and pathway evolution in nematodes

Abstract

The pathway that controls sexual fate in the nematode Caenorhabditis elegans has been well characterized at the molecular level. By identifying differences between the sex-determination mechanisms in C. elegans and other nematode species, it should be possible to understand how complex sex-determining pathways evolve. Towards this goal, orthologues of many of the C. elegans sex regulators have been isolated from other members of the genus Caenorhabditis. Rapid sequence evolution is observed in every case, but several of the orthologues appear to have conserved sex-determining roles. Thus extensive sequence divergence does not necessarily coincide with changes in pathway structure, although the same forces may contribute to both. This review summarizes recent findings and, with reference to results from other animals, offers explanations for why sex-determining genes and pathways appear to be evolving rapidly. Experimental strategies that hold promise for illuminating pathway differences between nematodes are also discussed.

Conspecific and Interspecific Interactions Between the FEM-2 and the FEM-3 Sex-Determining Proteins Despite Rapid Sequence Divergence

“…A C. briggsae fem-2 deletion produces mutant XX animals that develop into normal hermaphrodites, while mutant XO animals are feminized (R. Hill and E. Haag, personal communication). Cb-fem-3(RNAi) and Cb-fem-1(RNAi) also fail to interfere with hermaphrodite spermatogenesis (reviewed in Stothard and Pilgrim 2003). The C. remanei fem-2(RNAi) phenotypes observed in this study resemble those described for Cr-fem-3(RNAi) (Haag et al 2002) in that both lead to two-armed gonads and vulva-like structures but not to germline feminization.…”

“…Within worms, flies, and mammals the sex-determination pathways are largely conserved, although their constituent proteins show signs of rapid evolution. Both of these features of sex-determination evolution (the presence of distinct pathways in different phyla and rapid component divergence) may be consequences of genome conflict (Haag et al 2002;Stothard and Pilgrim 2003). Even without a good understanding of what forces are responsible for pathway differences, interspecies comparisons of sexdetermination may provide special insight into how regulatory networks can be assembled and modified.…”

“…We and others have begun to compare the C. elegans sex-determination pathway with the pathways that regulate sex in other nematode species such as C. briggsae and C. remanei (Stothard and Pilgrim 2003;Nayak et al 2005;Cutter and Ward 2005). Recent phylogenies for the various Caenorhabditis species have concluded that C. briggsae and C. elegans, which are both hermaphrodite/male species, diverged independently from gonochoristic (male/female) ancestors, and most of the closely related species, such as C. remanei, have retained that sex determining mechanism (Kiontke et al 2004;Cho et al 2004).…”

Profiling of gender-regulated gene transcripts in the filarial nematode Brugia malayi by cDNA oligonucleotide array analysis

“…Improved understanding of the reproductive biology of filarial worms may provide new insights into the epidemiology of filariasis and lead to new tools for controlling these diseases. Basic research may identify new targets for intervention that interfere with egg, microfilaria, or sperm production [1,2]. Filariasis researchers stand to benefit from extensive functional genomic studies that have been performed on the free-living nematode Caenorhabditis elegans [3,4].…”

Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans

“…A male phenotype, but not genotype, is required to confer resistance to C. neoformans-mediated killing: The molecular basis of sex determination in C. elegans has been well documented (Stothard and Pilgrim 2003) and centers around a repressor-based signal cascade. Briefly, in animals destined to become hermaphrodite (i.e., with two X chromosomes) the extracellular ligand HER-1 is not expressed and the transmembrane protein TRA-2 thus remains active, triggering a pathway that culminates in the activation of the transcription factor TRA-1 and the adoption of an hermaphrodite fate.…”