Gene Dmel\Sxl

General Information
Symbol	Dmel\Sxl	Species	D. melanogaster
Name	Sex lethal	Annotation symbol	CG18350
Feature type	protein_coding_gene	FlyBase ID	FBgn0003659
Created / Updated	2005-03-18/2005-03-18
Genomic Location
Chromosome (arm)	X	Recombination map	1-19.2
Cytogenetic map	6F3-6F5	Sequence location	X:6,969,698..6,992,086 [-]
Map ( GBrowse )
Summary Information
Automatically generated summary See sections below for more information	The gene Sex lethal is referred to in FlyBase by the symbol Sxl (CG18350, FBgn0003659). It has the cytological map location 6F3-6F5. Its sequence location is X:6969698..6992086. Its molecular function is described as: protein binding; poly-pyrimidine tract binding; mRNA binding; mRNA 5'-UTR binding; translation repressor activity, nucleic acid binding; growth factor activity; mRNA 3'-UTR binding; nucleotide binding. It is involved in the biological processes described with 20 unique terms, many of which group under: reproductive developmental process; mRNA metabolic process; multicellular organismal development; regulation of metabolic process; gamete generation; sex determination; negative regulation of nuclear mRNA splicing, via spliceosome; somatic sex determination; sexual reproduction; sex differentiation. 159 alleles are reported. The phenotypes of these alleles are annotated with 25 unique terms, many of which group under: organ system; adult segment; adult; anatomical structure; germarium; peripheral nervous system; adult mesothoracic segment; gamete; egg; blastoderm embryo; dorsal thoracic disc; karyosome. It has 15 annotated transcripts and 15 annotated polypeptides.
External Summaries

Phenotypic Description from the Red Book (Lindsley & Zimm 1992)
Gene/Allele symbols may differ from current usage	fs(1)K1274 Viability good at 29 but ovaries of homozygous females severely atrophied, probably with tumorous follicles. At 25 cysts contain 16 nurse cells and no oocyte; females fertile when raised at 23. Mosaic studies indicate germ-line function of gene (Perrimon and Gans, 1983, Dev. Biol. 100: 365-73). Sxl: Sex lethal (T.W. Cline) Sxl+ is a switch gene that acts throughout development to control all aspects of sexual dimorphism. Its products are required for female and must be absent for male development. Uniquely among sex-determination genes, after responding early in development to the primary sex-determination signal (the X:A ratio), Sxl maintains its own activity state as well as that of the downstream genes with which it interacts. It is required in a cell-autonomous fashion for both germ-line and somatic female development. It controls dosage compensation in females by suppressing hyperactivation of X-linked genes. Mutations of Sxl fall into two general classes: (1) recessive loss-of-function alleles that are deleterious to homozygous females, but viable and without phenotypic consequences in males, and (2) dominant gain-of-function alleles that behave as constitutive mutations, dominant and deleterious in males but without adverse effect in females, either heterozygous or homozygous. The variety of functions of the Sxl gene can be affected differentially by mutations, accounting in part for the complex complementation pattern observed for the large array of diverse mutant alleles. It is important to be aware that phenotypic parameters of mutant alleles and allele combinations can be very sensitive to culture conditions and genetic background. A number of positive regulators of Sxl are known, including the genes da, fs(1)A1621, sis-a, and sis-b. The female-specific lethal or sterile effects of mutations in these genes are suppressed by gain-of-function Sxl alleles. Throughout all but the very earliest period of development, female-specific expression of Sxl is known to be achieved by female-specific splicing of mRNA. The translation products from these female-spliced RNAs appear to help maintain the female-specific (productive) RNA processing mode which generates them, thereby establishing a positive feedback loop that maintains the female state throughout development. Sxlf1 Homozygous females invariably die as embryos but hemizygous males are fully viable and fertile. In most wildtype genetic backgrounds, heterozygous females exhibit normal viability and fertility, although occasionally display morphological defects characteristic of early cell death; however, can be dominant semilethal for females in some wild-type genetic backgrounds and under suboptimal growth conditions. In doubly heterozygous combination with otherwise recessive mutations in positive regulators of Sxl, this allele can behave as a dominant: heterozygote viability is reduced for daughters of da/+ females, as well as for females that are also heterozygotes for either sis-a, sis-b or fs(1)A1621. In some such doubly heterozygous situations, escaper females may be incompletely masculinized (mosaic intersex). Homozygosity for mutations in the autosomal male-specific lethal loci does not suppress recessive Sxlf1 lethality, but it does partially masculinize Sxlf1/+ females (generating mosaic intersexes) and suppresses cell-death-related morphological defects. Homozygous moribund embryos show sex-specific alterations in the phenotypic expression of hypomorphic X-linked alleles such as run25, a reflection of upsets in dosage compensation (female hyperactivation). Depending on the time of induction, Sxlf1/Sxlf1 clones induced in Sxlf1/+ females can be phenotypically male and reduced in size. 2X:3A animals homozygous or heterozygous for Sxlf1 are viable but masculinized. In genetic mosaics and chimeras, Sxlf1 homozygous germ cells develop abnormally and fail to generate functional gametes. In some situations, the mutant female tissue displays masculine traits. Sxlf1 rescues males from the otherwise lethal effects of a simultaneous duplication of sis-a+ and sis-b+. Sxlf2 Homozygous females are either inviable or very poorly viable, depending on genetic background. Escapers are invariably sterile but otherwise display no obvious sexual abnormalities. Complements Sxlf2593. Homozygotes defective in dosage compensation as indicated by hyperincorporation of uridine by their polytene chromosomes. Allele fails to support oogenesis in germ-line clones induced by mitotic recombination. Sxlf3 A hypomorphic allele selected as an intragenic suppressor of SxlM1 male lethality; maps 0.0065 cM to the right of SxlM1. Only characterized in cis combination with SxlM1. The double mutant is fully viable in males and poorly viable in homozygous females, with escapers being phenotypically male and sterile. Hemizygous females are lethal. Partially complements Sxlf2593, generating true intersexes. Partially complements Sxlf7,M1 with escapers phenotypically male and sterile. Fully complements Sxlfhv1. By itself, double mutant fails to bypass maternal da+ requirement for activation, but can complement Sxlf7,M1 in this regard. Double heterozygote with fs(1)A1621 is fertile. Sxlf7 A hypomorphic allele selected as an intragenic suppressor of SxlM1 male lethality; maps 0.0099 cM to the left of SxlM1. Only characterized in cis combination with SxlM1. The double mutant is male viable and semiviable in homozygous females. Escaper females are phenotypically male and sterile. Hemizygous females are inviable. Double heterozygote with fs(1)A1621 is sterile, like Sxlf1 but unlike SxlM1,f3. The double-mutant allele retains some ability to rescue daughters from the otherwise lethal maternal effect of da; however, lowering maternal da+ activity appears to decrease Sxlf7,M1 functioning, consistent with other evidence that the parental allele, SxlM1, is not fully constitutive. In the absence of a wild-type Sxl allele, Sxlf7,M1 daughters that survive the da maternal effect are phenotypically male and sterile; in contrast, the addition to this genotype of a wild-type Sxl allele in trans renders survivors phenotypically female, but still sterile with masculinized gonads. The latter genotype of female is fertile provided mothers carry at least one da+ allele. The ability of Sxlf7,M1 to rescue daughters is greatly enhanced by mutations in the autosomal, male-specific-lethal loci, genes involved in hyperactivation of X-linked genes in males. The basis for this enhancement is related to the ability of these same mutations to enhance the survival of Sxlf7,M1 hemizygous females. Although Sxlf7,M1 was used to demonstrate the ability of Sxl gene products to activate Sxl+ alleles in trans, it can be inferred that this allele is far below wild type in this activity. Sxlf7,M1 is a dominant suppressor of sis-a female-specific lethality, generating sterile females remarkably similar to those described above rescued from the da maternal effect. Unlike SxlM1,f3, fails to complement Sxlf2593; yet partially complements SxlM1,f3 and SxlfPb, generating sterile phenotypic males. Allele supports oogenesis in homozygous mutant germ-line clones induced by mitotic recombination. In males, mutant allele suppresses the otherwise lethal effect of a duplication of region 3C2-5A2; addition of Sxl+ to this aneuploid genotype generates mosaic intersexes indicating that the positive autoregulatory activity of Sxl products can bypass the X/A signal. Double heterozygote with fs(1)A1621 is sterile (like Sxlf1 and unlike SxlM1,f3). Sxlf9 A lethal hypomorphic allele defective in some very early steps in the sex-determination process, but which has no adverse effect on the growth or sexual development of homozygous mutant diplo-X clones induced by mitotic recombination. Rare escapers at 18 are phenotypically female; nevertheless, it has a dominant masculinizing effect on the phenotype of triploid intersexes (2X:3A) and interacts in a dominant-lethal fashion with mutations in da or sis-a, both early acting positive regulators of Sxl. Fully complements SxlfPR class (partial deletions of Sxl information that impair later functions of the gene more than earlier). Complements SxlM1,fPa-ra. Sxlf2593 A hypomorphic allele that is temperature sensitive for most Sxl functions. Perhaps most notable for the fact that homozygote viability can be quite high, with the females developing as true intersexes (their specific grade of inter-sexuality depends on temperature). Lethal over a deficiency, a null allele, or Sxlf7,M1 at any temperature; at permissive temperatures, weakly complements SxlM1,f3 and hypomorphic alleles of the SxlfPR class, generating (true) intersexual escapers; complementation better with SxlfPb, generating sterile females; fully complements Sxlf2, Sxlf9, and Sxlfhv1. Sxlfhv1 A subliminal allele, viable and fertile as homozygous females, but with greatly reduced viability in trans to nulls. Polytene chromosomes of Sxlfhv1/Sxlf1 larvae that survive to third instar hyperincorporate uridine, revealing female dosage compensation upsets. Mutation of mle appears to partially masculinize this heteroallelic combination and may slightly increase viability under some conditions. Sxlfhv1 homozygotes and heterozygotes display an increased requirement for maternal da+ activity, suggestive of defects in early Sxl regulation. SxlfLS A lethal hypomorphic allele that is able to initiate female development, but is defective in its ability to maintain the female developmental commitment and/or to elicit female sexual differentiation. It is masculinizing in homozygous mutant somatic clones induced by mitotic recombination, and it causes the tissue in such clones to grow poorly; nevertheless, it has no dominant effect on the sexual phenotype of triploid intersexes, nor does it interact in a dominant fashion with mutations in da or sis-a, both early acting positive regulators of Sxl. Fully complements Sxlf9, which appears to have a very different set of defects. SxlfP7BO Female-lethal null allele that appears to be deleted for the entire Sxl transcription unit. Males are fully viable, fertile, and display normal male sexual behavior. SxlfPa A hybrid-dysgenesis-induced apparent null allele selected as an intragenic suppressor of SxlM1 male lethality. Only characterized in cis combination with SxlM1. A P-element insertion 5' to the site of the DNA insertion in SxlM1 but still within the region of Sxl transcribed at all stages. Revertible. SxlfPa-ra A hybrid-dysgenesis-induced derivative of SxlM1,fPa selected for having regained the ability to complement Sxlf9. This complex allele disrupts both male and female development, with the magnitude of the effects in either sex depending on culture temperature in a reciprocal fashion: high temperature is more permissive for females and less permissive (more feminizing) for males. Intersexual males show little male sexual behavior and stimulate courtship from other males. Dominant male-lethal effects are greatly enhanced by the presence of a duplication of Sxl+ in trans; male escapers with both alleles exhibit an unusual dorsalization of the abdomen, their sternites being variably transformed into tergites. SxlfPb A P-insertion-induced lethal hypomorphic allele with the unusual distinction of displaying a mosaic intersex phenotype in homozygous mutant diplo-X clones induced by mitotic recombination; hence, appears to be defective in the cellular maintenance of the female sexual commitment. Under dysgenic conditions, can mutate further to less extreme or to more extreme condition. Partially complements Sxlf7,M1, generating masculinized individuals; partially complements Sxlf2593, generating sterile females; fully complements Sxlf9. SxlM1 Unconditionally lethal to males, even in the presence of a Sxl+ duplication. Retains normal level of female function as evidenced by full viability and fertility of homozygous and hemizygous mutant females. Recovered by virtue of ability to bypass the normal requirement by females for maternally supplied da+ product, a positive regulator of Sxl+; however, bypass is incomplete at higher temperatures. Phenotype in both sexes results from expression of Sxl+ female sex determination and dosage compensation functions largely (though not completely) independently of the normal controls. This is shown by the observation that induction of mutations in cis that suppress dominant, male-specific lethality is invariably associated with a corresponding reduction in Sxl+ female-specific activities and the dominant da maternal-effect bypass phenotype. SxlM1 is lethal to most gynandromorphs by the pharate-adult stage, disrupting the development of their haplo-X tissue in a cell-autonomous fashion; mutant haplo-X tissue in gynandromorphs is often, but not always, feminized. This variable penetrance of the sex transformation suggests a residual level of control by the X/A balance. SxlM1 feminizes triploid intersexes, killing them as pharate adults, while suppressing B and Hw alleles in a fashion consistent with expectations for constitutive expression of normal female dosage-compensation functions. Analysis of effects on the dosage compensation of the very early acting segmentation gene, run, suggests that constitutive expression of female functions is not observed prior to the time when the later Sxl promoter is required and RNA processing control is known to be operating. Since run dosage compensation during this period does require functioning of maternal da+, zygotic Sxl+, and the X/A balance, the ability of SxlM1 to bypass these controls during later stages of development would seem to indicate that the effect of the mutant lesion it carries is on Sxl-RNA splicing, a process that these other Sxl+ regulators may only affect indirectly. The position of the SxlM1 mutant lesion in the vicinity of the male-specific exon is suggestive in this connection. Variable expressivity of this mutant allele may underlie two additional observations: (1) SxlM1 male lethality can be suppressed by fs(1)A1621, yet fs(1)A1621 female sterility can be suppressed by SxlM1, and (2) transplants of SxlM1/Y and SxlM1/+ germ cells show that although the allele does not appear to interfere with spermatogenesis in testes, it blocks the otherwise masculinizing effect of testicular somatic tissue on diplo-X (female) germ cells.
Detailed Mapping Data
FlyBase Computed Cytological Location
Cytogenetic map Evidence for location 6F3-6F5 Limits computationally determined from genome sequence between P{EP}inx7^EP1641 and P{EP}CG9650^EP1340&P{EP}CG9650^EP1617
Experimentally Determined Cytological Location
Cytogenetic map Notes References 6F5-6F5 Determined by deficiency mapping (details unspecified). (Swan et al., 2001) 6F5-6F5 (determined by in situ hybridisation) 6F (determined by in situ hybridisation) (Maine et al., 1985)
Experimentally Determined Recombination Data
Location	1-19.2 (Nicklas and Cline, 1983, Sugimura et al., 1994)
Left of (cM)	ct (Sugimura et al., 1994) sn (Anand et al., 1998) v (Perrimon and Gans, 1983) l(1)air7 l(1)7Ad l(1)7Aa l(1)7Ab (Nicklas and Cline, 1983)
Right of (cM)	cv (Sugimura et al., 1994) ec (Perrimon and Gans, 1983) stout l(1)6Ea l(1)6Ed (Nicklas and Cline, 1983) cho (Anand et al., 1998)
Notes	Sxl lies in the middle of a 0.6cM stretch that appears to contain no genes vital to both sexes. (Nicklas and Cline, 1983) Recombination distance between Sxl^f9 and 'f3' of Sxl^M1,f3 is 0.015cM. Recombination distance between Sxl^f9 and Sxl^M1 is 0.007cM. (Bernstein and Cline, 1994)
Molecular Map Data
Gene Order (in direction of increasing cytology) References Gene Order (overall orientation not stated) References
Gene Model & Products
Please see the GBrowse view of Dmel\Sxl for information on other features
Comments on Gene Model
	gene_with_dicistronic_processed_transcript ; SO:0000722
Transcript Data
Annotated Transcripts
Name FlyBase ID RefSeq ID Length (nt) Associated CDS (aa) Sxl-RA FBtr0100200 NM_167115 2928 314 Sxl-RB FBtr0100201 NM_167118 2020 48 Sxl-RC FBtr0100202 NM_080052 1509 344 Sxl-RD FBtr0100203 NM_167112 3097 354 Sxl-RE FBtr0100205 NM_167113 2858 314 Sxl-RF FBtr0100206 NM_167117 3263 48 Sxl-RG FBtr0100207 NM_167116 3227 346 Sxl-RH FBtr0100208 NM_167114 5164 366 Sxl-RI FBtr0100209 NM_167111 1800 339 Sxl-RJ FBtr0100210 NM_167110 1934 346 Sxl-RK FBtr0100211 NM_001031895 2130 42 Sxl-RL FBtr0100212 NM_001031894 1854 354 Sxl-RM FBtr0100214 NM_001031893 5354 48 Sxl-RN FBtr0100215 NM_001031892 2752 344 Sxl-RO FBtr0100217 NM_001031891 4843 364
Additional Transcript Data & Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name FlyBase ID Predicted MW (kD) Length (aa) Theoretical pI RefSeq ID GenBank protein Sxl-PA FBpp0099570 34.3 314 9.71 NP_727165 AAO41638 Sxl-PB FBpp0099571 5.6 48 10.11 NP_727168 AAZ52514 Sxl-PC FBpp0099572 37.6 344 9.53 NP_524791 AAN09197 Sxl-PD FBpp0099573 38.5 354 9.84 NP_727162 AAG22410 Sxl-PE FBpp0099575 34.3 314 9.71 NP_727163 AAZ52512 Sxl-PF FBpp0099576 5.6 48 10.11 NP_727167 AAN09201 Sxl-PG FBpp0099577 37.6 346 9.79 NP_727166 AAN09200 Sxl-PH FBpp0099578 39.8 366 8.63 NP_727164 AAF46240 Sxl-PI FBpp0099579 37.0 339 9.82 NP_727161 AAF46241 Sxl-PJ FBpp0099580 37.6 346 9.79 NP_727160 AAN09198 Sxl-PK FBpp0099581 4.8 42 9.84 NP_001027066 AAZ52513 Sxl-PL FBpp0099582 38.5 354 9.84 NP_001027065 AAZ52511 Sxl-PM FBpp0099584 5.6 48 10.11 NP_001027064 AAG22411 Sxl-PN FBpp0099585 37.6 344 9.53 NP_001027063 AAZ52510 Sxl-PO FBpp0099587 39.8 364 8.11 NP_001027062 AAZ52509
Additional Polypeptide Data & Comments
Reported size (kD)	43 (kD) (Sakamoto et al., 1992) 39 (kD) (Valcarcel et al., 1993)
Comments	Sxl expression is derepressed in dpn null male embryos while the female embryo expression pattern is unchanged. Sxl was also misexpressed in embryos with altered dosage of the dpn and sc genes. (Younger-Shepherd et al., 1992) Sxl protein binds to the non-sex specific pyrimidine tract/3\\\' splice site of tra pre-mRNA blocking the binding of the U2AF splicing factor. It does not bind to the female specific splice site. (Valcarcel et al., 1993) The female specific form of the Sxl protein was shown to bind to the uridine rich sequences of the Sxl pre-mRNA by UV crosslinking experiments. (Sakamoto et al., 1992)
External Data
Linkouts
Crossreferences	InterPro domains - A database of protein families, domains, and functional sites • RNA recognition motif, RNP-1 (IPR000504) Paraneoplastic encephalomyelitis antigen (IPR002343) Sex-lethal splicing factor (IPR006546) Nucleotide-binding, alpha-beta plait (IPR012677) PDB - Protein Data Bank. An information portal to biological macromolecular structures • 1B7F 1SXL 2SXL 3SXL
Sequences Consistent with the Gene Model
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name AA438604 AA441208 AA802613 AE003439 AAF46240 AE003439 AAG22410 AE003439 AAG22411 AE003439 AAN09197 AE003439 AAN09198 AE003439 AAN09199 AE003439 AAO41637 AE003439 AAO41638 AE003439 AAO41639 AF295862 AI109579 AI257490 AI542033 AW942385 AY459615 AAS15801 AY459616 AAS15802 AY459617 AAS15803 AY459618 AAS15804 AY459619 AAS15805 AY459620 AAS15806 AY459621 AAS15807 AY459622 AAS15808 AY459623 AAS15809 AY459624 AAS15810 AY459625 AAS15811 AY459626 AAS15812 AY459627 AAS15813 AY459628 AAS15814 AY459629 AAS15815 AY459630 AAS15816 AY459631 AAS15817 AY459632 AAS15818 AY459633 AAS15819 AY459634 AAS15820 AY459635 AAS15821 AY459636 AAS15822 AY459637 AAS15823 AY459638 AAS15824 AY459639 AAS15825 AY459640 AAS15826 AY459641 AAS15827 AY459642 AAS15828 AY459643 AAS15829 AY459644 AAS15830 AY459645 AAS15831 AY459646 AAS15832 AY459647 AAS15833 AY459648 AAS15834 AY459649 AAS15835 AY459650 AAS15836 AY459651 AAS15837 AY459652 AAS15838 AY459653 AAS15839 AY459654 AAS15840 AY459655 AAS15841 AY459656 AAS15842 AY459657 AAS15843 AY459658 AAS15844 AY459659 AAS15845 AY459660 AAS15846 AY459661 AAS15847 AY459662 AAS15848 AY459663 AAS15849 AY459664 AAS15850 AY459665 AAS15851 AY459666 AAS15852 AY459667 AAS15853 AY459668 AAS15854 AY459669 AAS15855 AY459670 AAS15856 AY459671 AAS15857 AY459672 AAS15858 AY459673 AAS15859 AY459674