Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development
Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development
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DOI：
10.1093/cercor/bhu174
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发表时间：
2016-01-01
期刊：
影响因子：
3.7
通讯作者：
Giedd, Jay N.
中科院分区：
文献类型：
--
作者：
Raznahan, Armin;Lee, Nancy Raitano;Giedd, Jay N.
由于其独特的进化历史，现代哺乳动物的X染色体和Y染色体具有高度不同的基因内容，并被调节特征所平衡，这些特征优先限制X和Y特异性基因的表达。这两个特征对X与Y染色体对生物结构和功能的影响的预期不同做出了相反的预测。在这里，我们在一个罕见的人群中使用体内神经影像学定量这种差异性与不同的性染色体非整倍性（SCA）。我们发现，X-和Y-染色体对整体大脑大小有相反的影响，但对局部大脑解剖结构产生高度收敛的影响，这表现在大脑皮层的生物学上不同的维度上。对功能性神经影像学数据的大规模在线荟萃分析表明，会聚性染色体剂量效应优先影响社会感知、沟通和决策中心。因此，尽管几乎完全缺乏序列同源性，并且对整个大脑大小产生相反的影响，但X和Y染色体对参与适应性社会功能的皮质系统的比例大小产生一致的影响。这些会聚的X-Y效应（i）追踪X染色体和Y染色体仍然共享的少数基因的剂量，（ii）可能为SCA和精神病理学发病率增加之间的联系提供生物学基础。
Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X-Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.