title: Abundance of female-biased and paucity of male-biased somatically expressed genes on the mouse X-chromosome.
abstract: BACKGROUND
  Empirical evaluations of sexually dimorphic expression of genes on the mammalian X-chromosome are needed to understand the evolutionary forces and the gene-regulatory mechanisms controlling this chromosome. We performed a large-scale sex-bias expression analysis of genes on the X-chromosome in six different somatic tissues from mouse.
  
  
  RESULTS
  Our results show that the mouse X-chromosome is enriched with female-biased genes and depleted of male-biased genes. This suggests that feminisation as well as de-masculinisation of the X-chromosome has occurred in terms of gene expression in non-reproductive tissues. Several mechanisms may be responsible for the control of female-biased expression on chromosome X, and escape from X-inactivation is a main candidate. We confirmed escape in case of Tmem29 using RNA-FISH analysis. In addition, we identified novel female-biased non-coding transcripts located in the same female-biased cluster as the well-known coding X-inactivation escapee Kdm5c, likely transcribed from the transition-region between active and silenced domains. We also found that previously known escapees only partially explained the overrepresentation of female-biased X-genes, particularly for tissue-specific female-biased genes. Therefore, the gene set we have identified contains tissue-specific escapees and/or genes controlled by other sexually skewed regulatory mechanisms. Analysis of gene age showed that evolutionarily old X-genes (>100 myr, preceding the radiation of placental mammals) are more frequently female-biased than younger genes.
  
  
  CONCLUSIONS
  Altogether, our results have implications for understanding both gene regulation and gene evolution of mammalian X-chromosomes, and suggest that the final result in terms of the X-gene composition (masculinisation versus feminisation) is a compromise between different evolutionary forces acting on reproductive and somatic tissues.
authors.affiliation: Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden. bjorn.reinius@ki.se
authors.forename: Björn
authors.initials: B
authors.lastname: Reinius
authors.forename: Martin M
authors.initials: MM
authors.lastname: Johansson
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Radomska
authors.forename: Edward H
authors.initials: EH
authors.lastname: Morrow
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Pandey
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Kanduri
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Elena
authors.initials: E
authors.lastname: Jazin
mesh_terms: D000818:Animals; D015982:Bias; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050172:Genes, X-Linked; D056466:Histone Demethylases; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics; D014960:X Chromosome
chemical_list: D008565:Membrane Proteins; D056466:Histone Demethylases; C490173:Kdm5c protein, mouse; D010089:Oxidoreductases, N-Demethylating