Academic journal article Genetics

Analysis of the Sequence and Phenotype of Drosophila Sex Combs Reduced Alleles Reveals Potential Functions of Conserved Protein Motifs of the Sex Combs Reduced Protein

Academic journal article Genetics

Analysis of the Sequence and Phenotype of Drosophila Sex Combs Reduced Alleles Reveals Potential Functions of Conserved Protein Motifs of the Sex Combs Reduced Protein

Article excerpt

ABSTRACT

The Drosophila Hox gene, Sex combs reduced (Scr), is required for patterning the larval and adult, labial and prothoracic segments. Fifteen Scr alleles were sequenced and the phenotypes analyzed in detail. Six null alleles were nonsense mutations (Scr^sup 2^, Scr^sup 4^, Scr^sup 11^, Scr^sup 13^, Scr^sup 13A^, and Scr^sup 16^) and one was an intragenic deletion (Scr^sup 17^). Five hypomorphic alleles were missense mutations (Scr^sup 1^, Scr^sup 3^, Scr^sup 5^, Scr^sup 6^, and Scr^sup 8^) and one was a small protein deletion (Scr^sup 15^). Protein sequence changes were found in four of the five highly conserved domains of SCR: the DYTQL motif (Scr^sup 15^), YPWM motif (Scr^sup 3^), Homeodomain (Scr^sup 1^), and C-terminal domain (CTD) (Scr^sup 6^), indicating importance for SCR function. Analysis of the pleiotropy of viable Scr alleles for the formation of pseudotracheae suggests that the DYTQL motif and the CTD mediate a genetic interaction with proboscipedia. One allele Scr^sup 14^, a missense allele in the conserved octapeptide, was an antimorphic allele that exhibited three interesting genetic properties. First, Scr^sup 14^/Df had the same phenotype as Scr^sup +^/Df. Second, the ability of the Scr^sup 14^ allele to interact intragenetically with Scr alleles mapped to the first 82 amino acids of SCR, which contains the octapeptide motif. Third, Scr^sup 6^, which has two missense changes in the CTD, did not interact genetically with Scr^sup 14^.

THE Homeotic selector (Hox) genes are required for patterning the anterior-posterior axis of all bilateral animals (Lewis 1978; Carroll 1995). In Drosophila melanogaster, the Hox genes establish segmental identity in the embryo by controlling the spatial expression of target genes (Capovilla et al. 1994). Although much is known about the requirement of HOX activity in development, there is little known about internal domain structure of these proteins and how these transcription factors are regulated. In fact, the analysis of the functionaldomains ofHOXproteins has proven difficult and often contradictory (Zhao et al. 1996; Galant et al. 2002; Hittinger et al. 2005; Tour et al. 2005). For example, the insect specific QA motif of the HOX protein Ultrabithorax (UBX) is required for full Ubx repression of limb development in Drosophila when UBX is ectopically expressed (Galant and Carroll 2002; Ronshaugen et al. 2002). Noninsect UBX homologs lack aQA motif and lack the ability to suppress limb development when ectopically expressed in Drosophila; however, limb repression can be conferred to these noninsect UBX homologs by fusing the QA motif to the carboxyl termini (Galant and Carroll 2002). These ectopic expression experiments suggested that the QA motif was essential for UBX activity; therefore, it was surprising that a deletion of the QA motif within the Ubx locus produced only a subtle phenotype (Hittinger et al. 2005). The observation of differential pleiotropy in the Ubx and Antennapedia (Antp) loci offers a potential explanation for these difficulties: HOX proteins are made up of small independently acting peptide elements that alone make only a small contribution toHOX activity (Carroll 2005;Hittinger et al. 2005; Prince et al. 2008). Uniform pleiotropy is the same relative behavior of a set of alleles in a locus on two or more phenotypic characteristics, whereas, differential pleiotropy is a distinct relative behavior. Differential pleiotropy has been described in Ubx (Hittinger et al. 2005). Analysis of the Ubx-DQA allele revealed a differential requirement for the QAmotif in the development of various UBX-dependent tissues. This preferential requirement for the QA motif in a subset of tissues is an example of differential pleiotropy (Hittinger et al. 2005). In addition, the YPWM motif of theHOXprotein Antennapedia (ANTP), a motif that has been conserved across evolution in most HOX proteins, exhibits differential pleiotropy by being required for the formation of ectopic wing tissue but not the formation of ectopic leg tissue (Prince et al. …

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