同源染色体基因表达活性不同的现象,称为基因印记。据美国物理学家组织网报道,英国巴斯大学科学家近日发现了一种名为Grb10的基因,与通常的印记基因表达规则不符的是,它从父母双方遗传下来的等位基因作用截然不同。相关研究发表在近期出版的《自然》杂志上。
所有动物的细胞中,每个基因组都是成对出现:一条来自父亲,另一条来自母亲。多数情况下这两条基因都是活跃的,但对某些基因而言,其中一条被关闭了,基因仅能表达来自一方的同源基因,而另一方的不表达。
巴斯大学研究人员与加地夫大学神经系统科学与精神健康研究院科学家合作,发现了一种名为Grb10的基因,其异常之处在于,子代只在大脑中表达来自父方的基因,却在身体其他部位表达来自母方的基因——好像父母双方的印记基因各自在不同部位有一种无意识的优先权:母亲的基因表达涉及胎儿成长、新陈代谢、脂肪储存,而父亲的基因表达调控着成人的社会行为。
为了证实这一点,他们对缺乏父方Grb10基因的小鼠进行了行为研究。在一项强制遭遇测试中,研究人员将两组小鼠放置在一条狭窄管道的两端,并阻止它们转身,结果发现,Grb10基因在大脑中不活跃的小鼠通常会坚守原地,而其它小鼠则会倒退,并表现顺从。缺乏父方Grb10基因的小鼠更喜欢控制其它小鼠,与脑中父方Grb10基因活跃的小鼠相比,更有可能获得同伴礼貌的待遇,这在小鼠和其它哺乳动物中是一种处于统治地位的标志。此外,这些小鼠还更有可能扯断同笼的表达等位基因小鼠的胡须。当母方Grb10等位基因表达沉默时,小鼠通常会变得又大又重。
巴斯大学再生医学研究中心的安德鲁·沃德说:“这是首次,我们证明了同一个基因根据其来自父母双方的不同,可以有完全不同的功能。好像是父母双方以不同的策略来帮助后代,一方致力于身体,而另一方致力于精神。”
研究证明,印记基因对人类健康非常重要。Grb10与胚胎发育有关,而在后期生命中,它对身体和精神两方面都很重要。“一种基因能影响大脑和肌肉两方面是令人吃惊的。今后我们将研究Grb10基因如何进化出这种双重功能。”(生物谷Bioon.com)
生物谷推荐原文出处:
Nature doi:10.1038/nature09651
Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
Alastair S. Garfield,Michael Cowley,Florentia M. Smith,Kim Moorwood,Joanne E. Stewart-Cox,Kerry Gilroy,Sian Baker,Jing Xia,Jeffrey W. Dalley,Laurence D. Hurst,Lawrence S. Wilkinson,Anthony R. Isles& Andrew Ward
Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also postnatal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues.