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

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 the same phenotype as [Scr.sup.+]/Df. Second, the ability of the [Scr.sup.14] allele to interact intragenetically with Scralleles 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]. DOI: 10.1534/genetics.109.100438