The evolutionary meaning behind genetic variability lies in the ability of organisms to respond appropriately to stressful conditions. Different unfavorable environmental conditions can cause important effects on genome stability or activate and/or increase the activity of Transposable Elements (TEs), leading to heritable alterations in the structure of the genome. Environmental stress such as heat shock has recently been shown to influence silencing mechanisms, through the action of molecular chaperones such as Hsp70 and Hsp90, the latter involved in the biogenesis of piwi-interacting RNAs (piRNAs; a small, germ line-specific RNA), causing the activation of TEs and the onset of morphological anomalies due to insertional mutagenesis.
In light of that, I plan to test a different kind of stress, caused by the dysfunction of the biological clock, in order to understand the impact of circadian rhythms dysfunctions both in evolution and in human health, using Drosophila melanogaster as a model organism.
During the last few years, the advances obtained in this field of research suggest that circadian clocks have evolved to confer an adaptive advantage and aid organisms to efficiently organize the intricate relationships with the environment and their internal physiological processes. To date, the elucidation of the intricate relationship between intercellular circuitry and external input signals that affect circadian clocks, allows us to understand how normal circadian regulation of these processes promotes physiological homeostasis, and on the contrary, how circadian dysfunctions can negatively influence it and be associated with a wide variety of diseases, metabolic, cardiovascular, mental disorders and cancer.
There are profound effects of circadian clocks on our body that have now fully penetrated into human research, for this reason the study of the RTEs activation and DSB mechanisms, in response to particular circadian stress and/or sleep deprivation, could represent a further attractive strategy relates to the potential use of tagged molecular clock factors for the treatment of circadian disorders, as the deleterious effects on the health of shift workers, suggesting new applications for improving human health. In addition to this evidence, it may be very interesting to investigate the basis of the evolutionary benefits of maintaning functional circadian clocks. The increase in the transcription levels of certain TEs in response to stress conditions related to the effect that the circadian rhythm dysfunction can have, could result into a great push to genetic variation, improving the adaptability of individuals to different environments.
References:
1. Piscopo et al., Madridge J Clin Res, 2(1): 37-43, (2017)
2. Piscopo et al., Acta biochimica Polonica 65(2), (2018)
3. Notariale, Basile, Montana, Colonna Romano et al., Acta Biochim Pol, 65(4):585-594, (2018)
4. Biemont & Vieira, Nature, 443(7111):521-4, (2006)
5. Schmidt & Anderson, Biol Rev Camb Philos Soc, 81(4):531-543, (2006)
6. Ratner et al., Genetika Moscow, 28(3):68-86, (1992)
7. Specchia et al., Nature, 463(7281):666-665, (2010)
8. Fanti, Piacentini et al., Genetics, 206(4):1995-2006, (2017)
9. Cappucci et al., PNAS, 116(36):17943-17950, (2019)
10. Harrison, Kumar, Lang, Snyder & Gerstein, Nucleic Acid Research, 30(5)1083-1090, (2002)
11. Lloyd & Taylor, Ann N Y Acad Sci, 1184:1-20, (2010)
12. Pandey & Nichols, Pharmacol Rev, 63(2):411-36, (2011)
13. Reiter, Potocki, Chien, Gribskov & Bier, Genome Res, 11(6):1114-25, (2001)
14. Chien et al., Nucleic Acids Res, 30(1):149-51, (2002)
15. Konopka, Pittendrigh & Orr, J Neurogene, 6(1):1-10, (1989)
16. Konopka & Benzer, Proc Natl Acad Sci U S A, 68(9):2112-6, (1971)
17. Ozkaya & Rosato, Adv Genet, 77:79-123, (2012)
18. Allada et al., Cell, 93:791-804, (1998)
19. Ouyang et al., PNAS, 9(15)8660-8664, (1998)
20. Beaver et al., Proc Natl Acad Sci U S A, 99:2134-2139, (2002)
21. Krishnan et al., Aging, 1(11):937-948, (2009)
22. Rakshit et al., Chronobiol. Int., 29(1):5-14, (2012)
23. Antoch et al., Cell Cycle, 1197-204, (2008)
24. Koh et al., Science, 312(5781), (2006)
25. Luo, et al., Earth System Science Data, 4:47-73, (2012)
26. De Cecco et al., Aging (Albany NY), 5(12):867-83, (2013)
27. Deharo et al., Int J Cardiol, 172(1):1-2, (2014)
28. Mattis & Sehgal, Trends Endocrinol Metab, 27(4):192-203, (2016)
29. Krishnan et al., Biochem. Biophys. Res. Commun., 374(2):299-303, (2008)
30. Krishnan et al., Proc Natl Acad Sci U S A, 109(28):11172-7, (2012)
31. Bozzetti et al., J. Cell Sci, 128(11)2070-2084, (2015)
32. Specchia et al., Int. J. Mol. Sci., 18(5):1066, (2017)
33. Cusumano et al., Front. Physiol, 10:133, (2019)
34. Kaneko et al., J. Neurosci., 17(17):6745-6760, (1997)
35. Brand and Perrimon, Development, 118(2):401-415, (1993)
36. Belancio et al., Nucleic Acids Res, 3909-2, (2010)
37. Koike et al., Science, 338(6105):349-54, (2012)
38. Port and Bullock, Nat Methods, 13(10):852-854, (2016)
39. Rera et al., Cell Metabolism, 623-634, (2011)