Genomic Imprinting As a Window into Human Language Evolution

Humans spend large portions of their time and energy talking to one another, yet it remains unclear whether this activity is primarily selfish or altruistic. Here, it is shown how parent‐of‐origin specific gene expression—or “genomic imprinting”—may provide an answer to this question. First, it is shown why, regarding language, only altruistic or selfish scenarios are expected. Second, it is pointed out that an individual's maternal‐origin and paternal‐origin genes may have different evolutionary interests regarding investment into language, and that this intragenomic conflict may drive genomic imprinting which—as the direction of imprint depends upon whether investment into language is relatively selfish or altruistic—may be used to discriminate between these two possibilities. Third, predictions concerning the impact of various mutations and epimutations at imprinted loci on language pathologies are derived. In doing so, a framework is developed that highlights avenues for using intragenomic conflicts to investigate the evolutionary drivers of language.     

基因组印迹调节

虽然大多数哺乳动物基因都是双座位表达,但是有一少部分基因发生印迹,只有父母双方基因中的一个实际表达,这种表观遗传过程迁涉到发育不同阶段基因的表达调节,十分复杂,原则上印迹基因在生殖细胞中必须用表观遗传标记顺式标记,这些标记能够通过细胞分裂进行保存,在成熟生物分化细胞中能够指导多基因单座位表达,在生殖细胞形成早期两个座位上的表达差别必须消除,以便在成熟生殖细胞中重新设置印迹,在该文中,概述了目前所知介导这些过程的分子机制。     

Genomic Imprinting in Mammals

A review of the data on the mechanisms and effects of genomic imprinting, an epigenetic phenomenon regulating the development in placentate mammals, is presented. In contrast to the majority of gene loci with biallelic expression, the expression of imprinted loci is monoallelic. In humans and mice, more than 30 imprinted loci have been identified, in which maternal or paternal alleles may either be expressed or be found in a repressed state during ontogeny. Imprinting is established during gametogenesis, and the repression of an allele of the imprinted locus is determined by methylation of the key regulatory element of this allele. Both the maternal and paternal chromosome sets are required for normal development in mammals. This is why parthenogenesis and androgenesis in these animals are impossible in nature. As a result of differential gene expression of many imprinted loci, the balance of gene activity is established, which is necessary for normal proliferation and differentiation of various cell clones in embryogenesis. Many human developmental abnormalities and syndromes are determined by defective genomic imprinting. In particular, the loss of imprints, which is followed by the occurrence of biallelic expression of some imprinted loci, may cause malignant tumors.     

Genomic Imprinting in Mammals

Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs (lncRNAs). To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure. Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation.     

Evolutionary Aspects of Genomic Imprinting

Molecular Biology - Genomic imprinting is an epigenetic phenomenon that differentiates maternal and paternal copies of genes in the genome and causes monoallelic expression depending on parental...     

A Maternal–Offspring Coadaptation Theory for the Evolution of Genomic Imprinting

Imprinted genes are expressed either from the maternally or paternally inherited copy only, and they play a key role in regulating complex biological processes, including offspring development and mother–offspring interactions. There are several competing theories attempting to explain the evolutionary origin of this monoallelic pattern of gene expression, but a prevailing view has emerged that holds that genomic imprinting is a consequence of conflict between maternal and paternal gene copies over maternal investment. However, many imprinting patterns and the apparent overabundance of maternally expressed genes remain unexplained and may be incompatible with current theory. Here we demonstrate that sole expression of maternal gene copies is favored by natural selection because it increases the adaptive integration of offspring and maternal genomes, leading to higher offspring fitness. This novel coadaptation theory for the evolution of genomic imprinting is consistent with results of recent studies on epigenetic effects, and it provides a testable hypothesis for the origin of previously unexplained major imprinting patterns across different taxa. In conjunction with existing hypotheses, our results suggest that imprinting may have evolved due to different selective pressures at different loci.     

基因组印迹与种子发育

胚乳介导营养物质从母体到胚的转运过程,是开花植物中发生印迹的重要部位。胚乳的发育异常会导致胚的败育。在拟南芥中已鉴定到三个FIS (fertilization-independent seed) 基因,能制止无需受精即形成种子的发育过程,即FIS1/ MEDEA、FIS2和FIS3/FIE。其中MEDEA基因是胚乳发育的主要调控基因,在胚乳中被印迹。FWA基因也在胚乳中被印迹。系统阐述了植物基因组印迹的机理以及MEA和FWA印迹机制的研究进展,并介绍了印迹发生的亲本冲突学说、印迹的方式及其它已报道的印迹基因。     

基因组印记中的长非编码RNA

长非编码RNA(lnc RNA)是长度大于200 bp的一类非编码蛋白的RNA,因其在基因组中含量巨大以及重要的生物学功能引起了学术界的广泛关注.基因组印记是一种表观遗传现象,lnc RNAs通过建立靶基因的印记而发挥重要的生物功能.基因组印记可以用来研究lnc RNAs在转录和转录后水平调控基因表达的分子机制.本文选取6个印记机制研究比较透彻的印记区域,包括Kcnq1/Cdkn1c、Igf2r/Airn、Prader-Willi(PWS)/Angelman(AS)、Snurf/Snrpn、Dlk1-Dio3和H19/Igf2.通过介绍包括基因间lnc RNAs(H19、Ipw和Meg3)、反义lnc RNAs(Kcnq1ot1、Airn、Ube3a-ATS)和增强子lnc RNAs(IG-DMR e RNAs)在内的3种类型lnc RNAs在印记调控中的作用,从而了解lnc RNAs通过顺式或(/和)反式作用多种机制调控亲本特异性靶基因的表达.了解印记基因簇中lnc RNAs的作用方式将有助于我们揭示lnc RNAs在整个基因组中的作用机制.     

Population Genetic Models of Genomic Imprinting

The phenomenon of genomic imprinting has recently excited much interest among experimental biologists. The population genetic consequences of imprinting, however, have remained largely unexplored. Several population genetic models are presented and the following conclusions drawn: (i) systems with genomic imprinting need not behave similarly to otherwise identical systems without imprinting; (ii) nevertheless, many of the models investigated can be shown to be formally equivalent to models without imprinting; (iii) consequently, imprinting often cannot be discovered by following allele frequency changes or examining equilibrium values; (iv) the formal equivalences fail to preserve some well known properties. For example, for populations incorporating genomic imprinting, parameter values exist that cause these populations to behave like populations without imprinting, but with heterozygote advantage, even though no such advantage is present in these imprinting populations. We call this last phenomenon "pseudoheterosis." The imprinting systems that fail to be formally equivalent to nonimprinting systems are those in which males and females are not equivalent, i.e., two-sex viability systems and sex-chromosome inactivation.     

Epigenetic Mosaicism in Genomic Imprinting Disorders

Russian Journal of Genetics - Differential gene expression during development is maintained by complex regulatory epigenetic mechanisms that provide the formation of different specialized cell...     

基因组印迹的起动与沉默

在配子中基因组印迹起动复合物的结合引发印迹现象,印迹起动复合物中有多种可鉴定成分,存在结合的精确时间和机制,印迹起动复合物似乎仅出现在生殖细胞系,而甲基CpG结合蛋白则能延续增殖印迹,因此基因组印迹调节着发育基因或组织特异性单等位基因的瞬时表达及大染色体结构域中基因之间的相互作用 。     

基因印记与lncRNA

基因印记是一种表观遗传调控机制,在二倍体哺乳动物的发育过程中,基因印记可以调控来自亲代的等位基因差异表达。非编码RNA是不编码蛋白质的RNA,它在RNA水平调控基因表达。研究表明大多数印记基因中存在长非编码RNA（长度>200nt的非编码RNA）的转录,长非编码RNA主要通过顺式的转录干扰作用来实现基因印记。同时基因印记及其相关的长非编码RNA异常表达与许多先天疾病相关,迄今已发现数十种人类遗传疾病与基因印记有关,而lncRNA引起的基因印记在疾病的发生和治疗中起着重要作用。     

基因组印记对个体发育及动物克隆的影响

介绍了印记基因对个体发育及动物克隆的深远影响。通过分析有关印记基因起源的几种不同假说,展现印记基因的作用方式与功能;探讨印记基因特殊的形成机制,有助于深入理解这一表观遗传修饰调节对动物个体发育和动物克隆的影响。印记基因对哺乳动物胎儿的发育具有十分重要的作用,对个体的生长与行为也有一定影响,特别是对胎盘发育极为重要。一旦表达失控就会导致多种疾病发生,大量证据表明许多肿瘤的发生都与其相应基因组印记丢失有关。在当前动物克隆研究中,克隆动物成活率低,具有大量表型异常及不同程度缺陷,而这些异常与许多印记基因表达失调导致的症状非常相似。因此,克隆动物的印记基因表达异常可能正是制约克隆效率提高的关键因素。     

哺乳动物基因组印记的研究进展

基因组印记是由亲本来源不同而导致等位基因表达差异的一种遗传现象。基因组印记产生的原因及过程是现代遗传学的一个热点问题。哺乳动物的许多基因组印记特征都使其成为后基因组时代的一个热点生物学问题。进化的基因组印记在哺乳动物生殖、发育中起到了特定的作用。综述了基因组印记的特点、印记基因的印记机理、基因印记与克隆动物的发育、印记基因与疾病的研究进展。     

Genomic Imprinting and Problem of Parthenogenesis in Mammals

Genomic imprinting belongs by its nature to problems of epigenetics, which studies hereditary changes in gene expression not related to defective sequences of DNA nucleotides. Epigenetic mechanisms of control, including genomic imprinting, are involved in many processes of normal and pathological development of humans and animals. Disturbances of genomic imprinting may lead to various consequences, such as formation of developmental anomalies and syndromes in humans, appearance of the large offspring syndrome and increased mortality upon cloning of mammals, and death of parthenogenetic embryos soon after implantation and beginning of organogenesis. The death of diploid parthenogenetic or androgenetic mammalian embryos is determined by the absence of expression of the genes of imprinted loci of the maternal or paternal genome, which leads to significant defects in development of tissues and organs. A review is provided of the studies aimed at search of possible normalization of misbalanced gene activity and modulation of genomic imprinting effects during parthenogenetic development in mammals.__________Translated from Ontogenez, Vol. 36, No. 4, 2005, pp. 300–309.Original Russian Text Copyright © 2005 by Platonov.