• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Apr 2004; 166(4): 1761–1773.
PMCID: PMC1470811

The evolution of the Drosophila sex-determination pathway.

Abstract

The molecular complexity of the Drosophila somatic sex-determination pathway poses formidable intellectual challenges for attempts to explain its evolutionary origins. Here we present a reconstruction of how this regulatory cascade might have evolved in a step-by-step fashion. We illustrate how mutations in genes, which were already part of the pathway or were recruited as new regulators of the pathway, were favored by sexual selection acting on the discriminatory sex-determining signal. This allows us to explain the major features of the pathway, including multiple promoter sites, alternative splicing patterns, autoregulation, and stop codons. Our hypothesis is built on the available data from Drosophila and other insect species, and we point out where it is amenable to further experimental and comparative tests.

Full Text

The Full Text of this article is available as a PDF (141K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lenormand T, Raymond M. Resistance management: the stable zone strategy. Proc Biol Sci. 1998 Oct 22;265(1409):1985–1990. [PMC free article]
  • Baker BS, Wolfner MF. A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. Genes Dev. 1988 Apr;2(4):477–489. [PubMed]
  • Belote JM, McKeown M, Boggs RT, Ohkawa R, Sosnowski BA. Molecular genetics of transformer, a genetic switch controlling sexual differentiation in Drosophila. Dev Genet. 1989;10(3):143–154. [PubMed]
  • Beye Martin, Hasselmann Martin, Fondrk M Kim, Page Robert E, Omholt Stig W. The gene csd is the primary signal for sexual development in the honeybee and encodes an SR-type protein. Cell. 2003 Aug 22;114(4):419–429. [PubMed]
  • Bopp D, Calhoun G, Horabin JI, Samuels M, Schedl P. Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila. Development. 1996 Mar;122(3):971–982. [PubMed]
  • Charlesworth B. The evolution of chromosomal sex determination and dosage compensation. Curr Biol. 1996 Feb 1;6(2):149–162. [PubMed]
  • Christiansen Audrey E, Keisman Eric L, Ahmad Shaad M, Baker Bruce S. Sex comes in from the cold: the integration of sex and pattern. Trends Genet. 2002 Oct;18(10):510–516. [PubMed]
  • Cline TW. The Drosophila sex determination signal: how do flies count to two? Trends Genet. 1993 Nov;9(11):385–390. [PubMed]
  • Cline TW, Meyer BJ. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637–702. [PubMed]
  • Dübendorfer Andreas, Hediger Monika, Burghardt Géza, Bopp Daniel. Musca domestica, a window on the evolution of sex-determining mechanisms in insects. Int J Dev Biol. 2002 Jan;46(1):75–79. [PubMed]
  • Duboule D, Wilkins AS. The evolution of 'bricolage'. Trends Genet. 1998 Feb;14(2):54–59. [PubMed]
  • Erickson JW, Cline TW. Key aspects of the primary sex determination mechanism are conserved across the genus Drosophila. Development. 1998 Aug;125(16):3259–3268. [PubMed]
  • Estes PA, Keyes LN, Schedl P. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. Mol Cell Biol. 1995 Feb;15(2):904–917. [PMC free article] [PubMed]
  • Gebauer Fátima, Grskovic Marica, Hentze Matthias W. Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA. Mol Cell. 2003 May;11(5):1397–1404. [PubMed]
  • Hediger Monika, Burghardt Géza, Siegenthaler Christina, Buser Nathalie, Hilfiker-Kleiner Denise, Dübendorfer Andreas, Bopp Daniel. Sex determination in Drosophila melanogaster and Musca domestica converges at the level of the terminal regulator doublesex. Dev Genes Evol. 2004 Jan;214(1):29–42. [PubMed]
  • Heinrichs V, Ryner LC, Baker BS. Regulation of sex-specific selection of fruitless 5' splice sites by transformer and transformer-2. Mol Cell Biol. 1998 Jan;18(1):450–458. [PMC free article] [PubMed]
  • Hodgkin J. Genetic sex determination mechanisms and evolution. Bioessays. 1992 Apr;14(4):253–261. [PubMed]
  • Horabin JI, Schedl P. Sex-lethal autoregulation requires multiple cis-acting elements upstream and downstream of the male exon and appears to depend largely on controlling the use of the male exon 5' splice site. Mol Cell Biol. 1993 Dec;13(12):7734–7746. [PMC free article] [PubMed]
  • Sturtevant AH. A Gene in Drosophila Melanogaster That Transforms Females into Males. Genetics. 1945 May;30(3):297–299. [PMC free article] [PubMed]
  • Suzuki MG, Ohbayashi F, Mita K, Shimada T. The mechanism of sex-specific splicing at the doublesex gene is different between Drosophila melanogaster and Bombyx mori. Insect Biochem Mol Biol. 2001 Nov 1;31(12):1201–1211. [PubMed]
  • Kelley RL, Wang J, Bell L, Kuroda MI. Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature. 1997 May 8;387(6629):195–199. [PubMed]
  • Walker JJ, Lee KK, Desai RN, Erickson JW. The Drosophila melanogaster sex determination gene sisA is required in yolk nuclei for midgut formation. Genetics. 2000 May;155(1):191–202. [PMC free article] [PubMed]
  • Lucchesi JC. Dosage compensation in Drosophila and the "complex' world of transcriptional regulation. Bioessays. 1996 Jul;18(7):541–547. [PubMed]
  • Wilkins AS. Moving up the hierarchy: a hypothesis on the evolution of a genetic sex determination pathway. Bioessays. 1995 Jan;17(1):71–77. [PubMed]
  • Meise M, Hilfiker-Kleiner D, Dübendorfer A, Brunner C, Nöthiger R, Bopp D. Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica. Development. 1998 Apr;125(8):1487–1494. [PubMed]
  • Müller-Holtkamp F. The Sex-lethal gene homologue in Chrysomya rufifacies is highly conserved in sequence and exon-intron organization. J Mol Evol. 1995 Oct;41(4):467–477. [PubMed]
  • Nagoshi RN, Baker BS. Regulation of sex-specific RNA splicing at the Drosophila doublesex gene: cis-acting mutations in exon sequences alter sex-specific RNA splicing patterns. Genes Dev. 1990 Jan;4(1):89–97. [PubMed]
  • Nöthiger R, Steinmann-Zwicky M. A single principle for sex determination in insects. Cold Spring Harb Symp Quant Biol. 1985;50:615–621. [PubMed]
  • Ohbayashi F, Suzuki MG, Mita K, Okano K, Shimada T. A homologue of the Drosophila doublesex gene is transcribed into sex-specific mRNA isoforms in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol. 2001 Jan;128(1):145–158. [PubMed]
  • Pane Attilio, Salvemini Marco, Delli Bovi Pasquale, Polito Catello, Saccone Giuseppe. The transformer gene in Ceratitis capitata provides a genetic basis for selecting and remembering the sexual fate. Development. 2002 Aug;129(15):3715–3725. [PubMed]
  • Penalva LO, Sakamoto H, Navarro-Sabaté A, Sakashita E, Granadino B, Segarra C, Sánchez L. Regulation of the gene Sex-lethal: a comparative analysis of Drosophila melanogaster and Drosophila subobscura. Genetics. 1996 Dec;144(4):1653–1664. [PMC free article] [PubMed]
  • Raymond CS, Shamu CE, Shen MM, Seifert KJ, Hirsch B, Hodgkin J, Zarkower D. Evidence for evolutionary conservation of sex-determining genes. Nature. 1998 Feb 12;391(6668):691–695. [PubMed]
  • Raymond CS, Murphy MW, O'Sullivan MG, Bardwell VJ, Zarkower D. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev. 2000 Oct 15;14(20):2587–2595. [PMC free article] [PubMed]
  • Rice WR. Male fitness increases when females are eliminated from gene pool: implications for the Y chromosome. Proc Natl Acad Sci U S A. 1998 May 26;95(11):6217–6221. [PMC free article] [PubMed]
  • Saccone G, Peluso I, Artiaco D, Giordano E, Bopp D, Polito LC. The Ceratitis capitata homologue of the Drosophila sex-determining gene sex-lethal is structurally conserved, but not sex-specifically regulated. Development. 1998 Apr;125(8):1495–1500. [PubMed]
  • Schütt C, Nöthiger R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development. 2000 Feb;127(4):667–677. [PubMed]
  • Shearman DC, Frommer M. The Bactrocera tryoni homologue of the Drosophila melanogaster sex-determination gene doublesex. Insect Mol Biol. 1998 Nov;7(4):355–366. [PubMed]
  • Shen MM, Hodgkin J. mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Cell. 1988 Sep 23;54(7):1019–1031. [PubMed]
  • Sievert V, Kuhn S, Traut W. Expression of the sex determining cascade genes Sex-lethal and doublesex in the phorid fly Megaselia scalaris. Genome. 1997 Apr;40(2):211–214. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...