Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX).
Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX).
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DOI：
10.1186/1471-2164-9-65
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发表时间：
2008-02-05
期刊：
影响因子：
4.4
通讯作者：
Graves JA
中科院分区：
文献类型：
--
作者：
Delbridge ML;McMillan DA;Doherty RJ;Deakin JE;Graves JA
人类的X染色体含有偏向的基因。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，这解释了大量的与性别相关的精神发育迟滞(MRX)综合征。为了确定MRX基因是否被招募到X染色体，或者它们的大脑特定功能是否在重新定位到哺乳动物X染色体后获得，我们研究了它们的同源基因在有袋类动物中的位置和表达，这些有袋类动物大约在1.8亿年前从人类分离出来。我们分离并定位了9个Tammar Wallaby MRX同源物，发现其中6个位于Tammar Wallaby X(代表古老的保守哺乳动物X)上，3个位于5号染色体上，代表人类X染色体最近增加的区域。在人类和袋鼠中，MRX基因在相同的同义组中的位置不支持这样的假设，即在大脑中具有重要功能的基因是在从常染色体到哺乳动物X染色体的多个独立事件中招募的。大多数袋鼠MRX同源基因在袋鼠中的表达比在人类中更广泛。只有一个同源物，即Tammar Wallaby ARX同源物(位于Tammar染色体5p上)，具有与其在人类中相似的限制性表达模式。ARX在大脑中的特异性表达保持了1.8亿年，这表明该基因在哺乳动物大脑的发育和功能中发挥着重要作用。我们的结果表明，这项研究中的所有基因最初可能具有更一般的功能，在人类和其他胎盘哺乳动物的进化过程中，这些功能在大脑功能中变得更加特殊和重要。
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.
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影响因子：
2.6
作者：
Koina, E;Wakefield, MJ;Graves, JAM
通讯作者：
Graves, JAM
DOI：
10.1159/000059346
发表时间：
2001-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Kutsche, K;Gal, A
通讯作者：
Gal, A
DOI：
10.1111/j.1469-185x.1931.tb01030.x
发表时间：
1931-10-01
影响因子：
--
作者：
Fisher, RA
通讯作者：
Fisher, RA
DOI：
10.1006/bbrc.2000.2829
发表时间：
2000-06-07
影响因子：
3.1
作者：
Matsumoto, M;Saito, T;Furuichi, K
通讯作者：
Furuichi, K
影响因子：
2.6
作者：
Kitamura, K;Miura, H;Kato, K
通讯作者：
Kato, K