Chandra H S
Proc Natl Acad Sci U S A. 1985 Oct;82(20):6947-9. doi: 10.1073/pnas.82.20.6947.
The evolutionary function of X chromosome inactivation is thought to be dosage compensation. However, there is, at present, little evidence to suggest that most X chromosome-linked genes require such compensation. Another view--that X chromosome inactivation may be related to sex determination--is examined here. Consider a hypothetical DNA sequence regulating a major structural gene concerned with the determination of maleness. If this regulatory sequence occurs in both X and Y chromosomes and if its copy number in the Y chromosome is significantly greater than in the X chromosome, then the male-determining properties of the Y chromosome could be attributed to this higher copy number. On the other hand, if the Y chromosome has the same copy number of this sequence as the X chromosome, it is difficult to see how determination of two sexes would occur under such circumstances because XX and XY genomes would then be indistinguishable in this regard. Such a situation seems to occur in the human species with respect to the banded krait minor satellite, a repetitious DNA sequence associated with sex determination. This apparent difficulty may be resolved if X chromosome inactivation renders regulatory as well as structural genes nonfunctional and thereby brings about a significant reduction in the effective copy number of X chromosome-linked DNA sequences concerned with sex determination. It is suggested that X chromosome inactivation brings about, in this manner, a critical inequality between XX and XY embryos and that sex determination in humans is a consequence of this inequality. An analogous situation appears to exist in certain insects in which inactivation of a haploid set of chromosomes (and presumably, therefore, a 50% reduction in the effective copy number of most genes) is associated with maleness. If this line of reasoning is correct, it would suggest that sex determination may be the primary function of X chromosome inactivation.
X染色体失活的进化功能被认为是剂量补偿。然而，目前几乎没有证据表明大多数与X染色体连锁的基因需要这种补偿。本文探讨了另一种观点，即X染色体失活可能与性别决定有关。考虑一个假设的DNA序列，它调控着一个与雄性决定有关的主要结构基因。如果这个调控序列同时存在于X和Y染色体中，并且其在Y染色体中的拷贝数显著多于X染色体，那么Y染色体的雄性决定特性就可以归因于这种更高的拷贝数。另一方面，如果Y染色体中该序列的拷贝数与X染色体相同，那么在这种情况下就很难理解两性是如何确定的，因为在这方面XX和XY基因组将无法区分。在人类中，关于金环蛇小卫星（一种与性别决定相关的重复DNA序列）似乎就出现了这种情况。如果X染色体失活使调控基因和结构基因都失去功能，从而使与性别决定相关的X染色体连锁DNA序列的有效拷贝数大幅减少，那么这个明显的难题或许就能得到解决。有人提出，X染色体失活以这种方式导致XX和XY胚胎之间出现关键的不平等，而人类的性别决定就是这种不平等的结果。在某些昆虫中似乎也存在类似的情况，在这些昆虫中，一组单倍体染色体的失活（因此，大多数基因的有效拷贝数大概减少了50%）与雄性特征相关。如果这个推理思路是正确的，那就表明性别决定可能是X染色体失活的主要功能。
