Laboratoire de Biométrie et Biologie Évolutive, Centre National de la Recherche Scientifique, Université Lyon 1, Bat. Gregor Mendel, 16 rue Raphaël Dubois, 69622, Villeurbanne Cedex, France,
Cell Mol Life Sci. 2014 Apr;71(8):1383-94. doi: 10.1007/s00018-013-1499-6. Epub 2013 Oct 31.
Ohno's hypothesis states that dosage compensation in mammals evolved in two steps: a twofold hyperactivation of the X chromosome in both sexes to compensate for gene losses on the Y chromosome, and silencing of one X (X-chromosome inactivation, XCI) in females to restore optimal dosage. Recent tests of this hypothesis have returned contradictory results. In this review, we explain this ongoing controversy and argue that a novel view on dosage compensation evolution in mammals is starting to emerge. Ohno's hypothesis may be true for a few, dosage-sensitive genes only. If so few genes are compensated, then why has XCI evolved as a chromosome-wide mechanism? This and several other questions raised by the new data in mammals are discussed, and future research directions are proposed.
大野-常染色体假说认为，哺乳动物的剂量补偿在两个步骤中进化：两性中 X 染色体的两倍超活化以补偿 Y 染色体上的基因丢失，以及雌性中一条 X 染色体的沉默（X 染色体失活，XCI）以恢复最佳剂量。对这一假说的最近测试得到了相互矛盾的结果。在这篇综述中，我们解释了这一持续存在的争议，并认为哺乳动物剂量补偿进化的新观点正在开始出现。大野-常染色体假说可能仅适用于少数几个剂量敏感基因。如果只有少数几个基因得到补偿，那么为什么 XCI 会进化为一种全染色体机制呢？本文讨论了哺乳动物新数据提出的这一假说和其他几个问题，并提出了未来的研究方向。
