Holliday R
Symp Soc Exp Biol. 1984;38:381-94.
Four possible biological functions of meiosis are considered. First, the conventional view that it generates by recombination and sexual reproduction the genetic diversity on which natural selection can act. Second, that recombination at meiosis plays an important role in the repair of genetic defects in germ line cells. Third, that it is essential, at least in animals, for the reprogramming of gametes which give rise to the fertilized egg. Fourth, that it helps maintain the immortality of the germ line, possible by a process of rejuvenation involving the removal of faulty RNA and protein molecules, or by the elimination of defective meiocytes. A unified hypothesis is proposed which attempts to link these diverse functions. Evidence is now available which strongly indicates that the control of gene activity in higher organisms depends in part on the pattern of cytosine methylation in DNA, and that this pattern is inherited through the activity of a maintenance methylase. Epigenetic defects may arise by the loss of methyl groups which the methylase is unable to replace in somatic and also germ line cells, if de novo methylation cannot occur. There is also evidence that recombination at meiosis is largely confined to structural genes or adjacent DNA. It is proposed that the absence of a functionally important methyl group in a promotor or operater region produces a recombinator or signal for the initiation of recombination. The formation of hybrid DNA in this region then allows the lost methyl groups to be replaced by maintenance methylase activity. The removal of epigenetic defects by recombination during meiosis therefore becomes an essential part of a reprogramming and rejuvenation process. Assuming some epigenetic defects are nevertheless transmitted to the next generation, sexual reproduction and outbreeding would be advantageous because they provide the opportunity for their removal at the next meiosis. Inbreeding would be disadvantageous, because it increases the probability that epigenetic defects would become homozygous and could no longer be removed by recombination.
本文探讨了减数分裂可能具有的四种生物学功能。其一，传统观点认为减数分裂通过重组和有性生殖产生遗传多样性，而自然选择作用于这些遗传多样性。其二，减数分裂过程中的重组在生殖细胞系基因缺陷修复中发挥重要作用。其三，至少在动物中，减数分裂对于配子重编程至关重要，配子重编程会产生受精卵。其四，减数分裂有助于维持生殖细胞系的永生，这可能是通过一个涉及去除错误RNA和蛋白质分子的 rejuvenation 过程实现的，或者是通过消除有缺陷的减数分裂细胞来实现的。本文提出了一个统一的假说，试图将这些不同的功能联系起来。目前已有证据有力地表明，高等生物中基因活性的控制部分取决于DNA中胞嘧啶甲基化的模式，并且这种模式通过维持甲基化酶的活性得以遗传。如果不能发生从头甲基化，甲基化酶无法在体细胞和生殖细胞系细胞中替代丢失的甲基基团，就可能会出现表观遗传缺陷。还有证据表明，减数分裂过程中的重组主要局限于结构基因或相邻DNA。有人提出，启动子或操纵子区域中功能重要的甲基基团缺失会产生一个重组子或重组起始信号。该区域杂交DNA的形成随后允许维持甲基化酶活性替代丢失的甲基基团。因此，减数分裂过程中通过重组去除表观遗传缺陷成为重编程和 rejuvenation 过程的一个重要组成部分。假设一些表观遗传缺陷仍然会传递给下一代，有性生殖和远交将是有利的，因为它们为在下一次减数分裂时去除这些缺陷提供了机会。近亲繁殖将是不利的，因为它增加了表观遗传缺陷变得纯合且无法再通过重组去除的可能性。
