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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Curr Biol. Author manuscript; available in PMC 2010 September 1.
Published in final edited form as:
PMCID: PMC2931413

Convergent Evolution: Regulatory Lightning Strikes Twice


Nematodes of the genus Caenorhabditis have evolved self-fertile hermaphrodites several times. Like Caenorhabditis elegans, C. briggsae has also recruited an F-box protein to regulate the sex determination gene tra-2 during the evolution of self-fertilization.

Evolutionary biologists suffer from the lack of time machines. Until we get one, the details of how many adaptations evolved remain elusive. This is particularly true for developmental aspects, where we’d like to understand how the introduction of heritable variation and constraints imposed by developmental pathways interact with selection to produce a new phenotype. However, two favorable circumstances can offer something almost as good as a time machine: one is the existence of closely related organisms for whom lack of the adaptation in question is the primitive condition (i.e. ‘ancestor proxies’), and the other is replicated cases of the same adaptation evolving in related taxa (convergent or parallel evolution, depending on the details). For the evolution of self-fertility in the nematode genus Caenorhabditis both of these are available, and both are being used to considerable effect [1]. A new study [2] in this issue of Current Biology provides a fascinating example of how convergent evolution works at a molecular level.

In both animals and plants, sexuality generally requires mating between distinct individuals. In many species males and females produce sperm and eggs, respectively, while in others anatomically identical hermaphrodites exchange sperm in reciprocal fashion. More rarely, however, some organisms are hermaphrodites that fuse their own sperm and eggs together, allowing the animal to essentially have sex with itself. Though this extreme form of inbreeding known as ‘self-fertilization’ presents certain genetic problems, it also allows for a species to consistently reproduce at densities too low for reliably finding mates. The nematode C. elegans is the poster animal for such self-fertile hermaphroditism, which also has contributed to its success as a genetic model organism. However, this reproductive mode is rather exceptional in this group of nematodes and recently derived from an ancestor that had males and females [3,4]. Most species in the genus Caenorhabditis retain this ancestral system, and as a result have radically larger effective population sizes and more robust mating behaviors than C. elegans [5,6].

Much like C. elegans, its close relative C. briggsae evolved a strikingly similar form of self-fertile hermaphroditism [7]. In both species, animals with one X chromosome are males, while animals with two X chromosomes have a female body like their ancestors, yet produce a few hundred sperm before they switch permanently to oogenesis (Figure 1A). As a result, when males are absent, virgin hermaphrodites still produce abundant progeny. Much effort has gone into characterizing how C. elegans accomplishes this feat [8]. The genus Caenorhabditis as a whole, therefore, represents a model for studying the developmental genetic details of the repeated evolution of such a trait of major adaptive significance.

Figure 1
Hermaphroditism in Caenorhabditis nematodes.

Although a number of other systems of repeated evolution have been explored at the developmental level, XX spermatogenesis in Caenorhabditis is unusual in two ways: first, it involves the adaptive evolution of the germline as opposed to the soma. While novel somatic features may be produced to a large extent by the evolution of transcriptional control [9], germ cell differentiation relies heavily upon post-transcriptional regulation of mRNA stability and translation [10]. Second, it involves sex determination, one of the fastest evolving aspects of animal development [11]. One thus wonders whether the same types of genetic changes known to underlie the evolution of somatic morphology will also apply to the evolution of self-fertility, and also how reproducible the changes might be in independently evolved cases. The work of Guo et al. [2] sheds important light on both of these issues, and suggests that certain classes of proteins are especially susceptible to being co-opted into germline sex determination.

Guo et al. [2] began by screening for ‘atavistic’ mutations that converted C. briggsae hermaphrodites into true females. Mutations in one of the genes, she-1 (for spermless hermaphrodite), completely feminized the germ line of XX animals while allowing nearly normal levels of spermatogenesis in XO males. In this respect, she-1 is analogous to a gene in C. elegans, called fog-2, which encodes an F-box protein essential for hermaphrodite (but not male) spermatogenesis [12,13]. fog-2 is an evolutionary ‘smoking gun’: it is the product of a species-specific gene duplication, and has acquired unique sequences that allow it to help initiate XX spermatogenesis since that duplication [14]. Guo et al. [2] used recently developed genomic resources [15,16] to positionally clone she-1. Remarkably, she-1 also encodes a species-specific F-box protein, albeit one only distantly related to fog-2. As would be expected for an F-box protein, SHE-1 interacts with a core E3 ubiquitin ligase component, SKR-1, but the proteins it presumably helps target for ubiquitin-mediated degradation remain unknown. Thus, both C. elegans and C. briggsae incorporated a recently evolved F-box protein into their germline sex determination pathways in a way that promotes XX spermatogenesis.

Guo et al. [2] next used mutations in core C. briggsae sex determination genes [17,18] to examine at which point in the sex determination pathway she-1 acts to allow XX cells to assume a male fate. This revealed that she-1 behaves as a genetic repressor of the C. briggsae ortholog of tra-2, a female-promoting gene that encodes a membrane protein interacting with several other components of the sex determination pathway. This revealed another striking parallel with fog-2, which acts in C. elegans to repress tra-2 (in conjunction with the RNA-binding protein GLD-1) [12]. However, a major difference between fog-2 and she-1 is that while the former is absolutely required for all XX spermatogenesis, even null mutations of she-1 are temperature sensitive. Guo et al. [2] suggest the intriguing possibility that the incipient C. briggsae hermaphrodite initially lacked she-1, and was only able to reliably self-fertilize its eggs at cool temperatures.

With a substantial body of work on C. briggsae germline sex determination now in hand, we can ask how this species regulates XX spermatogenesis. A useful heuristic, and potentially biological construct here is that of a ‘sexual oscillator’ that first shifts XX germ cells to the male mode, and then precisely shifts them back to the female mode more consistent with X dosage (Figure 1B). Various C. briggsae mutants [17,19] suggest that this putative oscillator acts downstream of and is repressed in males by the fem genes, which encode cytoplasmic regulators of TRA-1 (the terminal transcription factor of the global sex determination pathway), and perhaps of other factors as well. The equivalent oscillator in C. elegans is inferred to lie further upstream, at the level of tra-2 and the fem genes [8]. However, in order for the oscillator to change the sex of gametes, the activity of various pathway components must be kept within certain limits. The female fate of germ cells in the XX ancestor presumably was highly reinforced, and this canalization may have to be softened to allow an oscillator to work reliably. This may be where she-1 comes in. The data of Guo et al. [2] are consistent with C. briggsae she-1 loss-of-function mutants being feminized because they have elevated Cb-tra-2 activity. This, in turn, would prevent the putative oscillator from reaching the threshold of maleness required to produce sperm. In other words, at high temperatures the oscillator in she-1 mutants oscillates, but to no avail. That she-1 males frequently produce oocytes late in life is consistent with this model: XO germ cells should be more strongly committed to the sperm fate than those of XX hermaphrodites, and thus loss of she-1 has a weaker effect in males.

Should we think of the evolution of selfing in C. elegans and C. briggsae as the same or different? We can say that in one major respect it is the same, in that there was a striking independent recruitment of an F-box protein to regulate the same core sex determination pathway gene, tra-2, in the hermaphrodites of both lineages. But we can also say it is substantially different, because while fog-2 appears to act on or be a part of the C. elegans sexual oscillator (Figure 1B), she-1 behaves like a factor that reinforces the commitment to a hermaphrodite development, but is not part of the putative oscillator itself. Recent experiments suggest that at least part of the C. briggsae oscillator regulates germline factors other than Cb-TRA-1 [19], and similar (but unknown) TRA-1-independent germline sex regulators have long been implicated in C. elegans [20]. This indicates that we have much to learn about the patterning of sexual fates in the Caenorhabditis germ line, and even more about how it evolves.


1. Haag E, Pilgrim D. Harnessing Caenorhabditis genomics for evolutionary developmental biology. Curr Genomics. 2005;6:579–588.
2. Guo Y, Lang S, Ellis RE. Independent recruitment of F box genes to regulate hermaphrodite development during nematode evolution. Curr Biol. 2009;19:1853–1860. [PubMed]
3. Cho S, Jin SW, Cohen A, Ellis RE. A phylogeny of Caenorhabditis reveals frequent loss of introns during nematode evolution. Genome Res. 2004;14:1207–1220. [PubMed]
4. Kiontke K, Gavin NP, Raynes Y, Roehrig C, Piano F, Fitch DH. Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss. Proc Natl Acad Sci USA. 2004;101:9003–9008. [PubMed]
5. Garcia LR, LeBoeuf B, Koo P. Diversity in mating behavior of hermaphroditic and male-female Caenorhabditis nematodes. Genetics. 2007;175:1761–1771. [PubMed]
6. Cutter AD, Dey A, Murray RL. Evolution of the Caenorhabditis elegans genome. Mol Biol Evol. 2009;26:1199–1234. [PubMed]
7. Nigon V, Dougherty E. Reproductive patterns annd attempts at reciprocal crossing of Rhabditis elegans Maupas, 1900, and Rhabditis briggsae Dougherty and Nigon, 1949 (Nematoda: Rhabditidae) J Exp Zool. 1949;112:485–503. [PubMed]
8. Kimble J, Crittenden SL. Controls of germline stem cells, entry into meiosis, and the sperm/oocyte decision in Caenorhabditis elegans. Annu Rev Cell Dev Biol. 2007;23:405–433. [PubMed]
9. Carroll SB. Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell. 2008;134:25–36. [PubMed]
10. Haag ES. Chapter 3. Caenorhabditis nematodes as a model for the adaptive evolution of germ cells. Curr Top Dev Biol. 2009;86:43–66. [PMC free article] [PubMed]
11. Wilkins A. The Evolution of Developmental Pathways. Sunderland, MA USA: Sinauer; 2002.
12. Clifford R, Lee M, Nayak S, Ohmachi M, Giorgini F, Schedl T. FOG-2, a novel F-box-containing protein, associates with the GLD-1 RNA-binding protein and directs male sex determination in the C. elegans hermaphrodite germline. Development. 2000;127:5265–5276. [PubMed]
13. Schedl T, Kimble J. fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans. Genetics. 1988;119:43–61. [PubMed]
14. Nayak S, Goree J, Schedl T. fog-2 and the evolution of self-fertile hermaphroditism in Caenorhabditis. PLoS Biol. 2005;3:e6. [PMC free article] [PubMed]
15. Hillier LW, Miller RD, Baird SE, Chinwalla A, Fulton LA, Koboldt DC, Waterston RH. Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny. PLoS Biol. 2007;5:e167. [PMC free article] [PubMed]
16. Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, Chen N, Chinwalla A, Clarke L, Clee C, Coghlan A, et al. The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol. 2003;1:166–192. [PMC free article] [PubMed]
17. Hill RC, de Carvalho CE, Salogiannis J, Schlager B, Pilgrim D, Haag ES. Genetic flexibility in the convergent evolution of hermaphroditism in Caenorhabditis nematodes. Dev Cell. 2006;10:531–538. [PubMed]
18. Kelleher DF, de Carvalho CE, Doty AV, Layton M, Cheng AT, Mathies LD, Pilgrim D, Haag ES. Comparative genetics of sex determination: masculinizing mutations in Caenorhabditis briggsae. Genetics. 2008;178:1415–1429. [PubMed]
19. Hill R, Haag E. A sensitized genetic background reveals evolution near the terminus of the Caenorhabditis germline sex determination pathway. Evol Dev. 2009;4:333–341. [PMC free article] [PubMed]
20. Hodgkin J. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics. 1986;114:15–52. [PubMed]