German J
New York Blood Center, NY 10021.
Am J Hum Genet. 1988 Mar;42(3):414-21.
In human somatic cells bearing two X chromosomes, one X is genetically inactivated throughout most of its length, whereas in cells with one X and one Y both sex chromosomes are active (with the exception of the constitutive heterochromatin of the Y that is inert). The vast base of information concerning normal and abnormal human sexual development that has accumulated since the advent of human cytogenetics 3 decades ago can be integrated by the following hypothesis: Homologous gonad-differentiation loci (GDLs) exist on the X and Y. The GDLs are strictly sex-linked; that is, normally they do not recombine during spermatogenesis, so that considerable divergence in DNA sequence doubtless has occurred between the locus on the X and the locus on the Y. The abundance of their evolutionarily conserved product--a substance still to be identified--determines the path of differentiation that the indifferent gonadal anlage of the early embryo will take: if only one GDL is transcribed, the case when two X chromosomes are present, ovary will develop; if two GDLs are transcribed, the case when a Y is present along with an X, testis will develop. By implication, facultative X inactivation is an integral and essential component of the system adopted in mammalian evolution for accomplishing gonadal--viz., sexual--dimorphism.
在携带两条X染色体的人类体细胞中，其中一条X染色体在其大部分长度上发生基因失活，而在具有一条X染色体和一条Y染色体的细胞中，两条性染色体都是活跃的（Y染色体的组成型异染色质除外，它是无活性的）。自30年前人类细胞遗传学出现以来积累的大量有关人类正常和异常性发育的信息，可以通过以下假说进行整合：X染色体和Y染色体上存在同源性腺分化基因座（GDLs）。GDLs严格与性别相关联；也就是说，在精子发生过程中它们通常不会发生重组，因此X染色体上的基因座与Y染色体上的基因座之间无疑在DNA序列上存在相当大的差异。它们进化上保守的产物——一种仍有待确定的物质——的丰度决定了早期胚胎未分化性腺原基将采取的分化路径：如果只有一个GDL被转录，即两条X染色体存在时的情况，卵巢将会发育；如果两个GDL都被转录，即一条Y染色体与一条X染色体同时存在时的情况，睾丸将会发育。这意味着，X染色体的随机失活是哺乳动物进化过程中为实现性腺——即性别——二态性所采用的系统中不可或缺的重要组成部分。
