Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX)

Margaret Delbridge, Daniel McMillan, Ruth Doherty, Janine Deakin, Jennifer Marshall Graves

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    Abstract

    Background: 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. Results: To 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 brainspecific expression of ARX over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function. Conclusion: Our 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.
    Original languageEnglish
    Pages (from-to)1-10
    Number of pages10
    JournalBMC Genomics
    Volume9:65
    DOIs
    Publication statusPublished - 2008

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    Chromosomes, Human, X
    Macropodidae
    Intellectual Disability
    Genes
    Mammalian Chromosomes
    Brain
    X Chromosome
    Mammals
    Synteny
    Marsupialia
    Chromosomes, Human, Pair 5
    Chromosomes

    Cite this

    Delbridge, Margaret ; McMillan, Daniel ; Doherty, Ruth ; Deakin, Janine ; Marshall Graves, Jennifer. / Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX). In: BMC Genomics. 2008 ; Vol. 9:65. pp. 1-10.
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    Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX). / Delbridge, Margaret; McMillan, Daniel; Doherty, Ruth; Deakin, Janine; Marshall Graves, Jennifer.

    In: BMC Genomics, Vol. 9:65, 2008, p. 1-10.

    Research output: Contribution to journalArticle

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    AB - Background: 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. Results: To 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 brainspecific expression of ARX over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function. Conclusion: Our 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.

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