Delbridge Margaret L, McMillan Daniel A, Doherty Ruth J, Deakin Janine E, Graves Jennifer A Marshall
Comparative Genomics Group, Research School of Biological Sciences, The Australian National University, Canberra, ACT 2601, Australia.
BMC Genomics. 2008 Feb 5;9:65. doi: 10.1186/1471-2164-9-65.
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.
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 brain-specific expression of ARX over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function.
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.
人类X染色体的基因含量存在偏向性。在人类X染色体上过度表达的一组基因是那些在大脑中表达的基因，这解释了大量的X连锁智力障碍（MRX）综合征。
为了确定MRX基因是被招募到X染色体上，还是它们的脑特异性功能是在转移到哺乳动物X染色体后获得的，我们研究了它们在有袋类动物中的直系同源基因的位置和表达，有袋类动物大约在1.8亿年前与人类分化。我们分离并定位了九个塔马尔沙袋鼠MRX同源基因，发现其中六个位于塔马尔沙袋鼠X染色体上（代表古老的保守哺乳动物X染色体），三个位于5号染色体上，代表人类X染色体最近添加的区域。人类和沙袋鼠中MRX基因在相同同线性组内的位置并不支持这样的假设，即在大脑中具有重要功能的基因是在多个独立事件中从常染色体被招募到哺乳动物X染色体上的。大多数塔马尔沙袋鼠MRX同源基因在塔马尔沙袋鼠中的表达比在人类中更广泛。只有一个，即塔马尔沙袋鼠ARX同源基因（位于塔马尔染色体5p上），具有与其在人类中的模式相当的受限表达模式。ARX基因在1.8亿年里保留了脑特异性表达，这表明该基因在哺乳动物大脑发育和功能中起基本作用。
我们的结果表明，本研究中的所有基因最初可能都具有更一般的功能，在人类和其他胎盘哺乳动物的进化过程中，这些功能在脑功能方面变得更加专门化和重要。
