Speculations on the role of natural antisense transcripts in mammalian X chromosome evolution

Recent comprehensive transcriptome analyses in mice have revealed tremendous numbers of natural antisense transcripts in a hitherto ignored category of genes in eukaryotes. We discuss the possible biological roles of these transcripts and their relationships with mammalian sex chromosome evolution. Of 60,770 full-length cDNA sequences, as many as 2,500 pairs of sense-antisense transcripts (SATs) with the potential to form RNA duplex via their complementary sequences have been identified. This high number of antisense transcripts indicates their generic roles in gene expression regulation. These SATs are almost evenly distributed along the chromosomes, with the exception of the X chromosome. The rate of occurrence of SATs on the X chromosome is one-third to one-half that on the autosomes, and this under-representation must be related to a property intrinsic to the X chromosome. Here we hypothesize that monoallelically expressed antisense RNA regulates its sense partner, but that this regulatory system cannot operate on the mammalian X chromosome, as the mammalian X chromosome is effectively in a hemizygous state in both sexes. Loss of such regulation may be involved in the evolution of the X chromosome itself.