Mitochondrial DNA and Type II Diabetes Mellitus

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Introduction


Evolution of Mitochondrial DNA

In 1966, Lynn Margulis wrote a paper entitled “On the Origin of Mitosing Cells”. In her paper, Margulis came up with an influential theory that has been shaping modern science ever since. Although it was hard for her to publish it in magazines, she was determined that the similarity between mitochondria and bacteria was far more meaningful than sheer coincidence.

Lynn Margulis. Taken at her conference at the III Congress about Scientific Vulgarization in La Coruña, Spain, on November 9, 2005. By Jpedreira - Self-published work by Jpedreira, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=407368

That theory is now famously known as the Endosymbiosis theory. Endosymbiosis explains the origin of eukaryotes. It is suggested that the first step in the origin of eukaryotes from prokaryotes was related to survival in the new oxygen-containing atmosphere: an aerobic prokaryotic microbe (i.e. the protomitochondrion) was ingested into the cytoplasm of a heterotrophic anaerobe. This endosymbiosis became obligate and resulted in the evolution of the first aerobic amitotic amoeboid organisms. By hypothesis, some of these amoeboids ingested certain motile prokaryotes. Eventually these, too, became symbiotic in their hosts. The association of the motile prokaryote with the amoeboid formed primitive amoeboflagellates. In these heterotrophic amoeboflagellates classical mitosis evolved. The evolution of mitosis, insuring an even distribution of large amounts of nucleic acid (i.e. host chromosomes containing host genes) at each cell division, must have taken millions of years. It most likely occurred after the transition to the oxidizing atmosphere, since all eukaryotic organisms contain mitochondria and are fundamentally aerobic. [1]


When the amoeboids ingested the prokaryotes, they also took in the genetic material of the prokaryotes. This genetic material is termed as mitochondrial DNA. A few years after the publication of the paper, scientists were able to study and sequence genomes of different species. In fact, the year 2014 saw more than a thousand new mitochondrial genome sequences deposited in GenBank—an almost 15% increase from the previous year. Hundreds of peer-reviewed articles accompanied these genomes, making mitochondrial DNAs (mtDNAs) the most sequenced and reported type of eukaryotic chromosome. [2]

The Human Mitochondrial DNA
The human mitochondrial DNA was sequenced and the different genes and their products-RNAs and tRNAs- are under constant study. The human mitochondrial DNA (mtDNA) is a double-stranded, circular molecule of 16 569 bp and contains 37 genes coding for two rRNAs, 22 tRNAs and 13 polypeptides. The mtDNA-encoded polypeptides are all subunits of enzyme complexes of the oxidative phosphorylation system. [3]

Table 1

The mitochondrial DNA encodes 13 mitochondrial proteins, which constitute critical parts of the electron transport chain.

Mitochondrial genes encoding proteins Gene name Gene bank ID Protein Complex MT-ND1 4535 NADH dehydrogenase 1 I MT-ND2 4536 NADH dehydrogenase 2 I MT-ND3 4537 NADH dehydrogenase 3 I MT-ND4 4538 NADH dehydrogenase 4 I MT-ND4L 4539 NADH 4L dehydrogenase I MT-ND5 4540 NADH dehydrogenase 5 I MT-ND6 4541 NADH dehydrogenase 6 I MT-CYB 4519 Cytochrome b III MT-CO1 4512 Cytochrome c oxidase I (COX1) IV MT-CO2 4513 Cytochrome c oxidase II (COX2) IV MT-CO3 4514 Cytochrome c oxidase III (COX3) IV MT-ATP6 4508 ATP synthase 6 V MT-ATP8 4509 ATP synthase 8 V The remainder of the 37 genes in mitochondrial DNA encodes tRNAs and rRNAs.



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Subscript: H2O
Superscript: Fe3+




Section 1 Genetics

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Section 2 Microbiome

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Conclusion

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References

  1. [Lynn Sagan, On the origin of mitosing cells, Journal of Theoretical Biology, Volume 14, Issue 3,1967,Pages 225-IN6,ISSN 0022-5193,https://doi.org/10.1016/0022-5193(67)90079-3.(http://www.sciencedirect.com/science/article/pii/0022519367900793)
  2. Smith DR. The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs?. Brief Funct Genomics. 2016;15(1):47–54. doi:10.1093/bfgp/elv027
  3. Jan-Willem Taanman, The mitochondrial genome: structure, transcription, translation and replication, Biochimica et Biophysica Acta (BBA) - Bioenergetics, Volume 1410, Issue 2,1999, Pages 103-123, ISSN 0005-2728, https://doi.org/10.1016/S0005-2728(98)00161-3.
  4. Hodgkin, J. and Partridge, F.A. "Caenorhabditis elegans meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.
  5. Bartlett et al.: Oncolytic viruses as therapeutic cancer vaccines. Molecular Cancer 2013 12:103.


Edited by [Beimnet Beyene Kassaye], student of Joan Slonczewski for BIOL 116 Information in Living Systems, 2019, Kenyon College.