Iwasa Y
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Curr Top Dev Biol. 1998;40:255-93. doi: 10.1016/s0070-2153(08)60369-5.
In some mammalian genes, paternally and maternally derived alleles are expressed differently: this phenomenon is called genomic imprinting. Several-explanations have been proposed for the observed patterns of genomic imprinting, but the most successful explanation is the genetic conflict hypothesis--natural selection operating on the gene expression produces the parental origin-dependent gene expression--because the paternally derived allele tends to be less related to the siblings of the same mother than the maternal allele and hence the paternal allele should evolve to be more aggressive in obtaining maternal resources. The successes and failures of this argument have been examined in explaining the observed patterns of genomic imprinting in mammals. After a brief summary of the observations with some examples, a quantitative genetic model describing the evolution of the cis-regulating element of a gene affecting the maternal resource acquisition was presented. The model supports the verbal argument that the growth enhancer should evolve to show imprinting with the paternal allele expressed and the maternal allele inactive, whereas a growth suppressor gene tends to have an inactive paternal allele and an active maternal allele. There are four major problems of the genetic conflict hypothesis. (1) Some genes affect embryonic growth but are not imprinted (e.g., Igf1), which can be explained by considering recessive, deleterious mutations on the coding regions, (2) A gene exists that shows the pattern that is a perfect reversal (Mash2), which is needed for placental growth, and yet has an active maternal allele and an inactive paternal allele. This can be explained if the overproduction of this gene causes dose-sensitive abortion to occur in early gestation. (3) Paternal disomies are sometimes smaller than normal embryos. This is a likely outcome of evolution if imprinted genes control the allocation between placenta and embryo by modifying the cell developmental fate. (4) Genes on X chromosomes do not follow the predictions of the genetic conflict hypothesis. For genes on X chromosomes, two additional forces of natural selection (sex differentiation and dosage compensation) cause genomic imprinting, possibly in the opposite direction. Available evidence suggests that these processes are stronger than the natural selection caused by female multiple mating. Finally, the same formalism of evolution can handle an alternative nonconflict hypothesis: genomic imprinting might have evolved because it reduces the risk of the spontaneous development of parthenogenetic embryo, causing a serious threat to the life of the mother (ovarian time bomb hypothesis). This hypothesis can also explain major patterns of genomic imprinting. In conclusion, the genetic conflict hypothesis is very successful in explaining the observed patterns of imprinting for autosomal genes and probably is the most likely evolutionary explanation for them. However, for genes on X chromosomes, other processes of natural selection are more important. Considering that a nonconflict hypothesis can also explain the patterns in principle, we need a quantitative estimate of various parameters, such as the rate of dose-dependent abortion, the degree of female promiscuity, and the rate of spontaneous development of the parthenogenetic embryo, in order to make judgments on the relative importance of different forces of natural selection to form genomic imprinting.
在一些哺乳动物基因中,来自父方和母方的等位基因表达不同:这种现象被称为基因组印记。针对观察到的基因组印记模式已提出了几种解释,但最成功的解释是遗传冲突假说——作用于基因表达的自然选择产生了依赖亲本来源的基因表达——因为父源等位基因与同一母亲的同胞的亲缘关系往往比母源等位基因与同胞的亲缘关系小,因此父源等位基因在获取母体资源方面应进化得更具“攻击性”。这一论点在解释哺乳动物中观察到的基因组印记模式时的成败已得到检验。在通过一些例子简要总结观察结果之后,提出了一个定量遗传模型,该模型描述了影响母体资源获取的基因的顺式调控元件的进化。该模型支持这样一种文字观点,即生长增强子应进化为表现出父源等位基因表达而母源等位基因不活跃的印记模式,而生长抑制基因往往父源等位基因不活跃而母源等位基因活跃。遗传冲突假说存在四个主要问题。(1)一些基因影响胚胎生长但没有印记(例如胰岛素样生长因子1),考虑到编码区的隐性有害突变,这一点可以得到解释;(2)存在一个基因表现出完全相反的模式(Mash2),这是胎盘生长所必需的,但其母源等位基因活跃而父源等位基因不活跃。如果该基因的过量产生导致妊娠早期发生剂量敏感型流产,这一点就可以得到解释。(3)父源二体有时比正常胚胎小。如果印记基因通过改变细胞发育命运来控制胎盘和胚胎之间的资源分配,那么这可能是进化的一个结果。(4)X染色体上的基因不遵循遗传冲突假说的预测。对于X染色体上的基因,另外两种自然选择力量(性别分化和剂量补偿)导致基因组印记,可能方向相反。现有证据表明,这些过程比雌性多次交配导致的自然选择更强。最后,相同的进化形式可以处理另一种非冲突假说:基因组印记可能已经进化,因为它降低了孤雌生殖胚胎自发发育的风险,这对母亲的生命构成严重威胁(卵巢定时炸弹假说)。这个假说也可以解释基因组印记的主要模式。总之,遗传冲突假说在解释观察到的常染色体基因印记模式方面非常成功,可能是对它们最有可能的进化解释。然而,对于X染色体上的基因,其他自然选择过程更重要。考虑到一个非冲突假说原则上也可以解释这些模式,我们需要对各种参数进行定量估计,例如剂量依赖性流产率、雌性滥交程度和孤雌生殖胚胎的自发发育率,以便判断不同自然选择力量对形成基因组印记的相对重要性。