Originally published as Genetics Published Articles Ahead of Print on November 17, 2008.

Genetics, Vol. 181, 421-434, February 2009, Copyright © 2009
doi:10.1534/genetics.108.096743

Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue Specificity and Evolutionary Conservation

Marina Telonis-Scott^*,, Artyom Kopp, Marta L. Wayne^*,, Sergey V. Nuzhdin^** and Lauren M. McIntyre^*,,,1

^* University of Florida Genetics Institute, University of Florida, Gainesville, Florida 32610-3610, Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 32610-0266, Department of Evolution and Ecology, University of California, Davis, California 95616, Department of Zoology, University of Florida, Gainesville, Florida 32611-8525, ^** Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089-2910 and Department of Statistics, University of Florida, Gainesville, Florida 32611-8545

¹ Corresponding author: 1376 Mowry Rd., CG Research Bldg., University of Florida, Gainesville, FL 32607.
E-mail: mcintyre{at}ufl.edu

Many genes in eukaryotic genomes produce multiple transcripts through a variety of molecular mechanisms including alternative splicing. Alternatively spliced transcripts often encode functionally distinct proteins, indicating that gene regulation at this level makes an important contribution to organismal complexity. The multilevel splicing cascade that regulates sex determination and sex-specific development in Drosophila is a classical example of the role of alternative splicing in cell differentiation. Recent evidence suggests that a large proportion of genes in the Drosophila genome may be spliced in a sex-biased fashion, raising the possibility that alternative splicing may play a more general role in sexually dimorphic development and physiology. However, the prevalence of sex-specific splicing and the extent to which it is shared among genotypes are not fully understood. Genetic variation in the splicing of key components of the sex determination pathway is known to influence the expression of downstream target genes, suggesting that alternative splicing at other loci may also vary in functionally important ways. In this study, we used exon-specific microarrays to examine 417 multitranscript genes for evidence of sex-specific and genotype-specific splicing in 80 different genotypes of Drosophila melanogaster. Most of these loci showed sex-biased splicing, whereas genotype-specific splicing was rare. One hundred thirty-five genes showed different alternative transcript use in males vs. females. Real-time PCR analysis of 6 genes chosen to represent a broad range of biological functions showed that most sex-biased splicing occurs in the gonads. However, somatic tissues, particularly adult heads, also show evidence of sex-specific splicing. Comparison of splicing patterns at orthologous loci in seven Drosophila species shows that sexual biases in alternative exon representation are highly conserved, indicating that sex-specific splicing is an ancient feature of Drosophila biology. To investigate potential mechanisms of sex-biased splicing, we used real-time PCR to examine the expression of six known regulators of alternative splicing in males vs. females. We found that all six loci are themselves spliced sex specifically in gonads and heads, suggesting that regulatory hierarchies based on alternative splicing may be an important feature of sexual differentiation.

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