title: Drosophila maleless gene counteracts X global aneuploid effects in males.
abstract: The loss of the entire X chromosome in Drosophila males generates a genome-wide aneuploid effect. We have employed a systems biology approach (microarray) to investigate the global aneuploid effect of the maleless (mle) mutation that disrupts the binding of male specific lethal (MSL) proteins that function in dosage compensation. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located mainly in the autosomes of Drosophila melanogaster. We found several such targets to be sensitive to the aneuploid effect and conserved with the X chromosome in primitive Drosophila species and Anopheles gambiae. During evolution, they shifted gradually from their X-chromosomal positions to the autosomes in the species D. melanogaster, suggesting that the counteraction of trans-acting regulatory modifiers and their targets in two separate chromosomes is evolutionarily advantageous. These findings suggest a remarkable and previously unexpected level of complexity favoring natural compensation for the aneuploid effect. We propose that the MSL complex functions in dosage compensation in two separate steps. Initially, X-linked genes including X-linked trans-acting modifiers are hyperactivated in dosage compensated males. Later, these compensated modifiers eventually mitigate inverse aneuploid effects for the equality in expression of their autosomal targets in males and females.
  
  
  
  Microarray data are available at the Gene Expression Omnibus (GEO) web deposit of National Centre for Biotechnology Information (NCBI) with the accession number GSE78227.
authors.affiliation: Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Hyderabad, India. utpal@ccmb.res.in.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Sumit G
authors.initials: SG
authors.lastname: Gandhi
authors.affiliation: Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Palaparthi
authors.affiliation: Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Balyan
authors.affiliation: Centre for Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, India. manikapb@gmail.com.
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000852:Anopheles / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D015870:Gene Expression; D017344:Genes, Insect; D008297:Male; D005810:Multigene Family; D009154:Mutation; D012727:Sex Characteristics; D049490:Systems Biology; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D014157:Transcription Factors; C070837:mle protein, Drosophila; D004265:DNA Helicases
keywords: Anopheles gambiae; Drosophila hyperactivation; autosome; evolutionary divergence; maleless mutation