人类 基因组 Project revealed that ~1-2% of our 基因组 makes functional proteins while the role of the remaining 98-99% remains enigmatic. Researchers have tried to uncover the mysteries surrounding the same and this article throws light on our understanding of its role and implications for human health and diseases.
From the time the Human 基因组 Project (HGP) was completed in April 20031, it was thought that by knowing the entire sequence of human genome which consists of 3 billion base pairs or ‘pair of letters’, 基因组 will be an open book using which researchers would be able to pin point exactly how a complex organism as a human being works which will eventually lead to finding our predispositions to various kinds of diseases, enhance our understanding of why disease occurs and finding cure for them as well. However, the situation became very perplexed when the scientists were only able to decipher only a part of it (only ~1-2%) which makes functional proteins that decide our phenotypic existence. The role of 1-2% of the DNA to make functional proteins follows the central dogma of molecular biology which states that DNA is first copied to make RNA, especially mRNA by a process called transcription followed by production of protein by mRNA by translation. In the language of the molecular biologist, this 1-2% of the human 基因组 codes for functional proteins. The remaining 98-99% is referred to as ‘junk DNA’ or ‘dark 问题’ which does not produce any of the functional proteins mentioned above and is carried as a ‘baggage’ every time a human being is born. In order to understand the role of the remaining 98-99% of the 基因组, ENCODE ( ENCyclopedia Of DNA Elements) project2 was launched in September 2003 by the National Human 基因组 Research Institute (NHGRI).
The ENCODE project findings have revealed that majority of the dark 问题’’ comprises of noncoding DNA sequences that function as essential regulatory elements by turning genes on and off in different type of cells and at different points in time. The spatial and temporal actions of these regulatory sequences is still not completely clear, as some of these (regulatory elements) are located very far away from the gene they act upon while in other cases they may be close together.
The composition of some of the regions of human 基因组 was known even before the launch of the Human 基因组 Project in that ~8% of the human 基因组 is derived from viral 基因组 embedded in our DNA as human endogenous retroviruses (HERVs)3. These HERVs have been implicated in providing innate immunity to humans by acting as regulatory elements for genes that control immune function. The functional significance of the this 8% was corroborated by the findings of the ENCODE project which suggested that majority of the ‘dark 问题 functions as regulatory elements.
In addition to the ENCODE project findings, a vast amount of research data is available from the past two decades suggesting a plausible regulatory and developmental role for the ‘dark 问题’. Using 基因组-wide association studies (GWAS), it has been identified that majority of the noncoding regions of DNA are associated with common diseases and traits4 这些区域的变异起到调节大量复杂疾病的发生和严重程度的作用，例如癌症、心脏病、脑部疾病、肥胖症等5,6. GWAS 研究还表明，基因组中的这些非编码 DNA 序列中的大多数被转录（从 DNA 转化为 RNA 但未翻译）为非编码 RNA，并且其调控的扰动导致不同的疾病影响7. 这表明非编码 RNA 在疾病发展中发挥调节作用的能力8.
此外，一些暗物质仍然是非编码 DNA，并以调节方式作为增强子发挥作用。 顾名思义，这些增强子通过增强（增加）细胞中某些蛋白质的表达来发挥作用。 最近的一项研究表明，DNA 非编码区的增强子效应使患者易患复杂的自身免疫性疾病和过敏性疾病，例如炎症性肠病9,10，从而导致确定用于治疗炎症性疾病的新的潜在治疗靶点。 “暗物质”中的增强子也与大脑发育有关，对小鼠的研究表明，这些区域的缺失会导致大脑发育异常11,12. 这些研究可能有助于我们更好地了解阿尔茨海默氏症和帕金森氏症等复杂的神经系统疾病。 “暗物质”也已被证明在血癌的发展中发挥作用13 如慢性粒细胞白血病（CML）和慢性淋巴细胞白血病（CLL）。
Thus, ‘dark matter’ represents an important part of the human 基因组 than previously realised and has directly influences human health by playing a regulatory role in the development and onset of human diseases as described above.
这是否意味着整个“暗物质”要么被转录成非编码 RNA，要么通过充当与人类各种疾病的易感性、发病和变异相关的调控元件而作为非编码 DNA 发挥增强作用？ 迄今为止进行的研究表明，同样的研究具有强大优势，未来几年更多的研究将帮助我们准确描绘整个“暗物质”的功能，这将导致确定新目标，希望找到治愈暗物质的方法。使人类衰弱的疾病。
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