Abstract
BackgroundThe human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes.ResultsTo determine if MRX genes were recruited to the X, or whether their brain-specific functions were acquired after relocation to the mammalian X chromosome, we examined the location and expression of their orthologues in marsupials, which diverged from human approximately 180 million years ago. We isolated and mapped nine tammar wallaby MRX homologues, finding that six were located on the tammar wallaby X (which represents the ancient conserved mammal X) and three on chromosome 5, representing the recently added region of the human X chromosome. The location of MRX genes within the same synteny groups in human and wallaby does not support the hypothesis that genes with an important function in the brain were recruited in multiple independent events from autosomes to the mammalian X chromosome. Most of the tammar wallaby MRX homologues were more widely expressed in tammar wallaby than in human. Only one, the tammar wallaby ARX homologue (located on tammar chromosome 5p), has a restricted expression pattern comparable to its pattern in human. The retention of the brain-specific expression of ARX over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function.ConclusionOur results suggest all the genes in this study may have originally had more general functions that became more specialised and important in brain function during evolution of humans and other placental mammals.
Highlights
The human X chromosome has a biased gene content
Attempts to prove that MRX genes are located disproportionately on the X have suffered from experimental ascertainment bias, since recessive MRX genes are more recognised in hemizygous males
(page number not for citation purposes) http://www.biomedcentral.com/1471-2164/9/65 genes on the wallaby 5p have a different expression pattern, this supports the hypothesis that the function of these genes has changed in the eutherian lineage upon relocation to the X chromosome. To test this hypothesis we studied a number of MRX genes, and candidate MRX genes involved in brain function distributed along the human X chromosome
Summary
The human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes. One analysis of the OMIM database corrected for any ascertainment bias by comparing the proportions of X-linked phenotypes of MR syndromes to that of other abnormalities [4]. Another analysis tested whether the over-representation of MRX syndromes would disappear if as yet unmapped MR genes were evenly distributed across the genome [5]. Both analyses concluded that mental retardation syndromes are significantly concentrated on the human X chromosome. Early spermatogonial genes, sex and reproduction related (SRR) and prostate-specific genes are over-represented on the X in humans and mice, whereas there is a paucity of genes involved in late spermatogenesis [6,7,8,9,10]
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