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基因构建中原始构件的概念以及由于寡核苷酸信号序列随机出现导致的转录和加工错误。

The notion of primordial building blocks in construction of genes and transcriptional and processing errors due to random occurrence of oligonucleotide signal sequences.

作者信息

Ohno S

出版信息

Adv Exp Med Biol. 1985;190:627-36. doi: 10.1007/978-1-4684-7853-2_34.

Abstract

Contrary to the currently popular belief, genes (flanking and internal noncoding sequences included) that specify beta-sheet and alpha-helical proteins are not unique sequences, rather they are degenerate repeats of short primordial building block sequences that are 45 to 48 bases long in the case of genes belonging to the beta-2-microglobulin superfamily. Accordingly, a large number of base decamers, nonomers, octamers, heptamers and hexamers recur within every gene. One consequence of the above is the random and inadvertent occurrence within genes of various oligonucleotide signal sequences for initiation and termination of transcription as well as for processing of transcripts by removal of intervening sequences. Inadvertent transcription of nonsense sequences and missplicing of transcripts may increase with age and contribute to the aging process. There is little doubt that the life span, being one of the species' characteristics, is genetically programmed. The question remains, however, as to whether or not such a program is embodied in each and every somatic cell type. If the cessation of cell proliferation is regarded synonymous with senescence, one is placed in the awkward position of having to state that most neurons of the central nervous system enter the state of senescence at the neonatal stage. An alternative to the above is the assumption of central control; e.g., the programmed secretion of an aging peptide hormone by the pituitary. To be sure somatic cells accumulate randomly sustained mutations as do germ cells and whatever other genetic mishaps (e.g., deletions, duplications) that may affect somatic cells also occur in germ cells. Yet, the monophyletic germ line on this earth has persisted for three billion years and has the potential of being immortal. Furthermore there can be no direct cause-and-effect relationship between the process of differentiation and the loss of immortality, for spermatozoa are one of the most, if not the most, differentiated cell types that can be found in the body. Nevertheless, if one's scope is confined to the types of genetic mishaps that may afflict somatic cells in their given life span, the one particular type that has hitherto escaped notice should be considered.

摘要

与当前流行的观点相反,指定β折叠和α螺旋蛋白的基因(包括侧翼和内部非编码序列)并非独特序列,而是短原始构建块序列的简并重复,对于属于β-2-微球蛋白超家族的基因而言,这些序列长度为45至48个碱基。因此,大量的十聚体、九聚体、八聚体、七聚体和六聚体在每个基因中反复出现。上述情况的一个后果是,各种寡核苷酸信号序列在基因内随机且意外地出现,用于转录的起始和终止以及通过去除间隔序列来加工转录本。无义序列的意外转录和转录本的错误剪接可能会随着年龄增长而增加,并导致衰老过程。毫无疑问,寿命作为物种的特征之一,是由基因编程的。然而,问题仍然在于,这样的程序是否体现在每一种体细胞类型中。如果将细胞增殖的停止视为衰老的同义词,那么就会陷入一个尴尬的境地,即不得不指出中枢神经系统的大多数神经元在新生儿阶段就进入衰老状态。上述情况的另一种选择是假设存在中央控制;例如,垂体程序性分泌一种衰老肽激素。可以肯定的是,体细胞会像生殖细胞一样随机积累持续的突变,并且任何可能影响体细胞的其他遗传事故(例如缺失、重复)也会在生殖细胞中发生。然而,地球上的单系生殖系已经存在了30亿年,并且有永生的潜力。此外,分化过程与永生的丧失之间不可能存在直接的因果关系,因为精子是体内可以找到的最分化(如果不是最分化)的细胞类型之一。然而,如果将范围局限于在给定寿命内可能困扰体细胞的遗传事故类型,那么迄今为止未被注意到的一种特殊类型应该被考虑。

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