Academic journal article Genetics

Comparative Genetics of Sex Determination: Masculinizing Mutations in Caenorhabditis Briggsae

Academic journal article Genetics

Comparative Genetics of Sex Determination: Masculinizing Mutations in Caenorhabditis Briggsae

Article excerpt

ABSTRACT

The nematodes Caenorhabditis elegans and C. briggsae independently evolved self-fertile hermaphroditism from gonochoristic ancestors. C. briggsae has variably divergent orthologs of nearly all genes in the C. elegans sex determination pathway. Their functional characterization has generally relied on reverse genetic approaches, such as RNA interference and cross-species transgene rescue and more recently on deletion mutations. We have taken an unbiased forward mutagenesis approach to isolating zygotic mutations that masculinize all tissues of C. briggsae hermaphrodites. The screens identified loss-of-function mutations in the C. briggsae orthologs of tra-1, tra-2, and tra-3. The somatic and germline phenotypes of these mutations are largely identical to those of their C. elegans homologs, including the poorly understood germline feminization of tra-1(lf) males. This overall conservation of Cb-tra phenotypes is in contrast to the fem genes, with which they directly interact and which are significantly divergent in germline function. In addition, we show that in both C. briggsae and C. elegans large C-terminal truncations of TRA-1 that retain the DNA-binding domain affect sex determination more strongly than somatic gonad development. Beyond these immediate results, this collection of mutations provides an essential foundation for further comparative genetic analysis of the Caenorhabditis sex determination pathway.

UNLIKE many other developmental processes, such as anterior/posterior patterning and appendage specification, sex determination varies greatly between different phyla (e.g., De Rosa et al. 1999; Zarkower 2001; Panganiban and Rubenstein 2002). Both environmental sex determination and genetic sex determination (GSD) exist, the latter being the better characterized of the two since it is used by most genetic model species. However, even within GSD systems, diversity is extreme. For example, in both mammals and Drosophila, females are XX and males are XY, but in mammals themale dominant Y chromosomedetermines sex through the action of SRY (Sinclair et al. 1990; Koopman et al. 1991; Graves 2002), while in Drosophila the X-toautosome (X:A) ratio determines sex through the differential splicing of dsx (Schutt and Nothiger 2000). In hymenopteran insects such as the honeybee, males are haploid for the entire genome, with heterozygosity at a highly polymorphic locus determining femaleness (Beye et al. 2003; reviewed by Cook 1993). Most nematodes employ an XX/XO system in which females (or hermaphrodites) are XX and males are XO. Like Drosophila, sex determination in nematodes proceeds through assessment of the X:A ratio (Nigon 1951; Madl and Herman 1979). However, unlike Drosophila, the nematode responds toX dosage through a cell-nonautonomous negative regulatory cascade that probably represents a highly modified version of the hedgehog-signaling pathway (Cline and Meyer 1996; Haag and Pilgrim 2005).

Despite the above variety, the discovery that dsx in Drosophila melanogaster, mab-3 in Caenorhabditis elegans, and DMRTI in humans are all homologs with sex determination functions (Raymond et al. 1998) suggests that the various sex determination systems are derived from a common ancestral system and that this deep homology has become virtually unrecognizable at both the sequence and pathway levels (Zarkower 2001; Matsuda et al. 2002; Miller et al. 2003; Haag and Doty 2005). Because of its organismal importance and rapid change, sex determination presents a fascinating opportunity for studying the evolution of development. However, given the rapidity with which sex determination evolves, comparisons between different phyla yield little or no information about the process of change. In contrast, comparisons between closely related species are ideal for addressing this. C. elegans is one of the beststudied sex determination models, and its congeners offer such comparisons on both the molecular and the developmental genetic level (reviewed by Haag 2005; Haag and Pilgrim 2005). …

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