The Binadamu Genome Project revealed that ~1-2% of our genome 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 binadamu health and diseases.
From the time the Binadamu Genome Project (HGP) was completed in April 20031, it was thought that by knowing the entire sequence of binadamu genome which consists of 3 billion base pairs or ‘pair of letters’, genome will be an open book using which researchers would be able to pin point exactly how a complex organism as a binadamu 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 binadamu genome codes for functional proteins. The remaining 98-99% is referred to as ‘junk DNA’ or ‘dark jambo’ which does not produce any of the functional proteins mentioned above and is carried as a ‘baggage’ every time a binadamu being is born. In order to understand the role of the remaining 98-99% of the genome, ENCODE ( ENCyclopedia Of DNA Elements) project2 was launched in September 2003 by the National Binadamu Genome Research Institute (NHGRI).
The ENCODE project findings have revealed that majority of the dark jambo’’ 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 binadamu genome was known even before the launch of the Binadamu Genome Project in that ~8% of the binadamu genome is derived from viral genomes embedded in our DNA as binadamu endogenous retroviruses (HERVs)3. These HERVs have been implicated in providing innate immunity to binadamu 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 jambo 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 jambo’. Using Genome-wide association studies (GWAS), it has been identified that majority of the noncoding regions of DNA are associated with common diseases and traits4 na tofauti katika maeneo haya hufanya kazi kudhibiti mwanzo na ukali wa idadi kubwa ya magonjwa changamano kama vile saratani, magonjwa ya moyo, matatizo ya ubongo, fetma, kati ya mengine mengi.5,6. Tafiti za GWAS pia zimefichua kuwa mifuatano hii mingi ya DNA isiyoweka misimbo katika jenomu hunakiliwa (kubadilishwa kuwa RNA kutoka kwa DNA lakini haijatafsiriwa) kuwa RNA zisizo na misimbo na kuvurugwa kwa udhibiti wake husababisha athari za magonjwa tofauti.7. Hii inaonyesha uwezo wa RNA zisizo na coding kuchukua jukumu la udhibiti katika maendeleo ya ugonjwa huo8.
Zaidi ya hayo, baadhi ya mambo meusi yanasalia kama DNA isiyoweka misimbo na hufanya kazi kwa njia ya udhibiti kama viboreshaji. Kama neno linavyopendekeza, viboreshaji hivi hufanya kazi kwa kuimarisha (kuongeza) usemi wa protini fulani kwenye seli. Hii imeonyeshwa katika utafiti wa hivi majuzi ambapo athari za kiboreshaji za eneo lisilo la kuweka alama kwenye DNA huwafanya wagonjwa kuathiriwa na magonjwa changamano ya autoimmune na mzio kama vile ugonjwa wa uchochezi wa bowel.9,10, na hivyo kusababisha kutambuliwa kwa lengo jipya la matibabu kwa ajili ya matibabu ya magonjwa ya uchochezi. Viimarishi katika 'dark matter' pia vimehusishwa katika ukuaji wa ubongo ambapo tafiti za panya zimeonyesha kuwa kufutwa kwa maeneo haya husababisha ukiukaji wa ukuaji wa ubongo.11,12. Masomo haya yanaweza kutusaidia kuelewa vyema magonjwa changamano ya neva kama vile Alzheimers na Parkinson. 'Dark matter' pia imeonyeshwa kuwa na jukumu katika ukuzaji wa saratani za damu13 kama vile leukemia ya muda mrefu ya myelocytic (CML) na leukemia ya muda mrefu ya lymphocytic (CLL).
Thus, ‘dark matter’ represents an important part of the binadamu genome than previously realised and has directly influences binadamu afya by playing a regulatory role in the development and onset of binadamu diseases as described above.
Does that mean that the entire ‘dark matter’ is either transcribed into non-coding RNAs or play an enhancer role as non-coding DNA by acting as regulatory elements associated with predisposition, onset and variations in the various diseases inflicting binadamu? The studies performed till now show a strong preponderance for the same and more research in the coming years will help us exactly delineate the function of the entire ‘dark matter’, that will lead to identification of novel targets in the hope of finding cure to the debilitating diseases that inflict the human race.
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Marejeo:
1. “Human Genome Project Completion: Frequently Asked Questions”. National Human Genome Research Institute (NHGRI). Available online at https://www.genome.gov/human-genome-project/Completion-FAQ Ilifikiwa tarehe 17 Mei2020.
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3. Soni R., 2020. Wanadamu na Virusi: Historia Fupi ya Uhusiano Wao Mgumu na Athari kwa COVID-19. Scientific European Ilitumwa tarehe 08 Mei 2020. Inapatikana mtandaoni kwa https://www.scientificeuropean.co.uk/humans-and-viruses-a-brief-history-of-their-complex-relationship-and-implications-for-COVID-19 Ilifikiwa tarehe 18 Mei 2020.
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5. Katalogi ya Mafunzo ya Ushirika Uliochapishwa wa Genome-Wide. http://www.genome.gov/gwastudies.
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7. St. Laurent G, Vyatkin Y, na Kapranov P. Dark matter RNA huangazia fumbo la masomo ya muungano wa jenomu kote. BMC Med 12, 97 (2014). DOI: https://doi.org/10.1186/1741-7015-12-97
8. Martin L, Chang HY. Kufunua jukumu la "jambo la giza" la genomic katika ugonjwa wa binadamu. J Clin Wekeza. 2012;122 (5): 1589 1595-. https://doi.org/10.1172/JCI60020
9. Taasisi ya Babraham 2020. Kufichua jinsi sehemu za 'maada ya giza' ya jenomu huathiri magonjwa ya uchochezi. Ilichapishwa tarehe 13 Mei, 2020. Inapatikana mtandaoni kwa https://www.babraham.ac.uk/news/2020/05/uncovering-how-dark-matter-regions-genome-affect-inflammatory-diseases Ilifikiwa tarehe 14 Mei 2020.
10. Nasrallah, R., Imianowski, CJ, Bossini-Castillo, L. et al. 2020. Kiboreshaji cha mbali kilicho hatarini 11q13.5 hukuza ukandamizaji wa colitis na seli za Treg. Asili (2020). DOI: https://doi.org/10.1038/s41586-020-2296-7
11. Dickel, DE et al. 2018. Viboreshaji vilivyohifadhiwa sana vinahitajika kwa maendeleo ya kawaida. Seli 172, Toleo la 3, P491-499.E15, Januari 25, 2018. DOI: https://doi.org/10.1016/j.cell.2017.12.017
12. 'Jambo la giza' DNA huathiri ukuaji wa ubongo DOI: https://doi.org/10.1038/d41586-018-00920-x
13. Mambo ya giza: Kubagua saratani za damu hila kwa kutumia DNA DOI yenye giza zaidi: https://doi.org/10.1371/journal.pcbi.1007332
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