The advent of high-throughput technologies to analyze RNA expression levels and transcript structure has brought renewed attention to the age-old question of what differentiates males from females. In Drosophila, the characterized somatic sex determination cascade includes proteins implicated in the regulation of pre-mRNA splicing as well as at least 2 transcription factors at its base. Both DNA microarrays and RNA-Seq have been applied in a number of studies to determine the identities, expression levels and structure of transcripts expressed differentially in the 2 sexes, with remarkably divergent results in the number, structure and identity of affected transcripts. We briefly summarize these reports and discuss the reasons for the apparent discrepancies based upon the different conditions used for sample preparation and data analysis.

1.
Anand A, Villella A, Ryner LC, Carlo T, Goodwin SF, et al: Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless. Genetics 158:1569-1595 (2001).
2.
Arbeitman MN, Fleming AA, Siegal ML, Null BH, Baker BS: A genomic analysis of Drosophila somatic sexual differentiation and its regulation. Development 131:2007-2021 (2004).
3.
Arbeitman MN, Furlong EEM, Imam F, Johnson E, Null BH, et al: Gene expression during the life cycle of Drosophila melanogaster. Science 297:2270-2275 (2002).
4.
Assis R, Zhou Q, Bachtrog D: Sex-biased transcriptome evolution in Drosophila. Genome Biol Evol 4:1189-1200 (2012).
5.
Barmina O, Gonzalo M, McIntyre LM, Kopp A: Sex- and segment-specific modulation of gene expression profiles in Drosophila. Dev Biol 288:528-544 (2005).
6.
Belote JM, Handler AM, Wolfner MF, Livak KJ, Baker BS: Sex-specific regulation of yolk protein gene expression in Drosophila. Cell 40:339-348 (1985).
7.
Bopp D: About females and males: continuity and discontinuity in flies. J Genet 89:315-323 (2010).
8.
Burtis KC, Baker BS: Drosophiladoublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56:997-1010 (1989).
9.
Burtis KC, Coschigano KT, Baker BS, Wensink PC: The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. EMBO J 10:2577-2582 (1991).
10.
Celniker SE, Sharma S, Keelan DJ, Lewis EB: The molecular genetics of the bithorax complex of Drosophila: cis-regulation in the Abdominal-B domain. EMBO J 9:4277-4286 (1990).
11.
Chang PL, Dunham JP, Nuzhdin SV, Arbeitman MN: Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing. BMC Genomics 12:364 (2011).
12.
Chatterjee SS, Uppendahl LD, Chowdhury MA, Ip PL, Siegal ML: The female-specific doublesex isoform regulates pleiotropic transcription factors to pattern genital development in Drosophila. Development 138:1099-1109 (2011).
13.
Chau J, Kulnane LS, Salz HK: Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis. Proc Natl Acad Sci USA 109:9465-9470 (2012).
14.
Concha C, Scott MJ: Sexual development in Lucilia cuprina (Diptera, Calliphoridae) is controlled by the transformer gene. Genetics 182:785-798 (2009).
15.
Coschigano KT, Wensink PC: Sex-specific transcriptional regulation by the male and female doublesex proteins of Drosophila. Genes Dev 7:42-54 (1993).
16.
Daines B, Wang H, Wang L, Li Y, Han Y, et al: The Drosophila melanogaster transcriptome by paired-end RNA sequencing. Genome Res 21:315-324 (2011).
17.
Douglas SJ, Levine JD: Sex cells: dissecting the functions of fruitless isoforms. Curr Biol 16:R405-R407 (2006).
18.
Erdman SE, Chen HJ, Burtis KC: Functional and genetic characterization of the oligomerization and DNA binding properties of the Drosophila doublesex proteins. Genetics 144:1639-1652 (1996).
19.
Fujii S, Amrein H: Genes expressed in the Drosophila head reveal a role for fat cells in sex-specific physiology. EMBO J 21:5353-5363 (2002).
20.
Gempe T, Beye M: Function and evolution of sex determination mechanisms, genes and pathways in insects. Bioessays 33:52-60 (2011).
21.
Goldman TD, Arbeitman MN: Genomic and functional studies of Drosophila sex hierarchy regulated gene expression in adult head and nervous system tissues. PLoS Genet 3:e216 (2007).
22.
González AN, Lu H, Erickson JW: A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination. Proc Natl Acad Sci USA 105:18436-18441 (2008).
23.
Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, et al: The developmental transcriptome of Drosophila melanogaster. Nature 471:473-479 (2011).
24.
Gummalla M, Maeda RK, Castro Alvarez JJ, Gyurkovics H, Singari S, et al: abd-A regulation by the iab-8 noncoding RNA. PLoS Genet 8:e1002720 (2012).
25.
Hardin PE: Molecular genetic analysis of circadian timekeeping in Drosophila. Adv Genet 74:141-173 (2011).
26.
Hartmann B, Castelo R, Blanchette M, Boue S, Rio DC, Valcárcel J: Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophila cells. Genome Biol 10:R11 (2009).
27.
Hartmann B, Castelo R, Miñana B, Peden E, Blanchette M, et al: Distinct regulatory programs establish widespread sex-specific alternative splicing in Drosophila melanogaster. RNA 17:453-468 (2011).
28.
Hashiyama K, Hayashi Y, Kobayashi S: DrosophilaSex lethal gene initiates female development in germline progenitors. Science 333:885-888 (2011).
29.
Heinrichs V, Ryner LC, Baker BS: Regulation of sex-specific selection of fruitless 5′ splice sites by transformer and transformer-2. Mol Cell Biol 18:450-458 (1998).
30.
Hempel LU, Oliver B: Sex-specific DoublesexM expression in subsets of Drosophila somatic gonad cells. BMC Dev Biol 7:113 (2007).
31.
Hilgers V, Perry MW, Hendrix D, Stark A, Levine M, Haley B: Neural-specific elongation of 3′ UTRs during Drosophila development. Proc Natl Acad Sci USA 108:15864-15869 (2011).
32.
Horabin JI: Splitting the Hedgehog signal: sex and patterning in Drosophila. Development 132:4801-4810 (2005).
33.
Hughes ME, Grant GR, Paquin C, Qian J, Nitabach MN: Deep sequencing the circadian and diurnal transcriptome of Drosophila brain. Genome Res 22:1266-1281 (2012).
34.
Karch F, Weiffenbach B, Peifer M, Bender W, Duncan I, et al: The abdominal region of the bithorax complex. Cell 43:81-96 (1985).
35.
Lam BJ, Bakshi A, Ekinci FY, Webb J, Graveley BR, Hertel KJ: Enhancer-dependent 5′-splice site control of fruitless pre-mRNA splicing. J Biol Chem 278:22740-22747 (2003).
36.
Luo SD, Shi GW, Baker BS: Direct targets of the D. melanogaster DSXF protein and the evolution of sexual development. Development 138:2761-2771 (2011).
37.
McIntyre LM, Bono LM, Genissel A, Westerman R, Junk D, et al: Sex-specific expression of alternative transcripts in Drosophila. Genome Biol 7:R79 (2006).
38.
Mihailovic M, Wurth L, Zambelli F, Abaza I, Militti C, et al: Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR. RNA 18:53-64 (2012).
39.
Nagoshi RN, McKeown M, Burtis KC, Belote JM, Baker BS: The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster. Cell 53:229-236 (1988).
40.
Pane A, Salvemini M, Delli Bovi P, Polito C, Saccone G: The transformer gene in Ceratitis capitata provides a genetic basis for selecting and remembering the sexual fate. Development 129:3715-3725 (2002).
41.
Parisi M, Nuttall R, Edwards P, Minor J, Naiman D, et al: A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol 5:R40 (2004).
42.
Robinett CC, Vaughan AG, Knapp JM, Baker BS: Sex and the single cell. II. There is a time and place for sex. PLoS Biol 8:e1000365 (2010).
43.
Saccone G, Salvemini M, Polito LC: The transformer gene of Ceratitis capitata: a paradigm for a conserved epigenetic master regulator of sex determination in insects. Genetica 139:99-111 (2011).
44.
Salz HK, Erickson JW: Sex determination in Drosophila: the view from the top. Fly 4:60-70 (2010).
45.
Sánchez L: Sex-determining mechanisms in insects. Int J Dev Biol 52:837-856 (2008).
46.
Shirangi TR, Dufour HD, Williams TM, Carroll SB: Rapid evolution of sex pheromone-producing enzyme expression in Drosophila. PLoS Biol 7:e1000168 (2009).
47.
Song HJ, Billeter JC, Reynaud E, Carlo T, Spana EP, et al: The fruitless gene is required for the proper formation of axonal tracts in the embryonic central nervous system of Drosophila. Genetics 162:1703-1724 (2002).
48.
Tarone AM, Nasser YM, Nuzhdin SV: Genetic variation for expression of the sex determination pathway genes in Drosophila melanogaster. Genet Res 86:31-40 (2005).
49.
Telonis-Scott M, Kopp A, Wayne ML, Nuzhdin SV, McIntyre LM: Sex-specific splicing in Drosophila: widespread occurrence, tissue specificity and evolutionary conservation. Genetics 181:421-434 (2009).
50.
Traut W, Niimi T, Ikeo K, Sahara K: Phylogeny of the sex-determining gene Sex-lethal in insects. Genome 49:254-262 (2006).
51.
Venables JP, Klinck R, Bramard A, Inkel L, Dufresne-Martin G, et al: Identification of alternative splicing markers for breast cancer. Cancer Res 68:9525-9531 (2008).
52.
Williams TM, Selegue JE, Werner T, Gompel N, Kopp A, Carroll SB: The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134:610-623 (2008).
53.
Yang Y, Graze RM, Walts BM, Lopez CM, Baker HV, et al: Partitioning transcript variation in Drosophila: abundance, isoforms, and alleles. G3 1:427-436 (2011).
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