Digital Biology Friday: The importance of being aerobic

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Sandra Porter
If we compare sections 1, 2, and 3, we see that section 2 matches very well in a number of different samples, and that there are differences between the sequences in sections 1 and 3. i-bed5846063bbebc59fa0a4516d917562-small_mito_mut.gif We also learn something about the people who did the experiment. At first it appears somewhat odd that there are many matching sequences that are all shorter than the genome and all the same length. What's up with that? It turns out that information doesn't have anything to do with the fraction of the genome that matches our query. These short segments are PCR products. They're the same size because the PCR reactions were all done with the same primers. Part of the goal of these experiments was to characterize the genetic diversity of the great apes and see how the different species are related. It's cheaper to do this with shorter bits of DNA than sequencing entire mitochondrial genomes, and thus, we have lots of PCR data. But why are the sequences in section 2 so similar and the sequences in sections 1 and 3, so different? A likely explanation is that there is a reason why the sequences in section 2 don't show much (or any) change and why the the sequences in section 3 are free to do so. To understand the reason for the differences, I looked at the blastn results to learn if a gene mapped to section 2 and the identity of that gene. You can see how to do that here. The gene in section 2 codes for NADH dehydrogenase subunit 5. NADH dehydrogenase subunit 5 is a protein that works with 41 other proteins, in a huge complex (respiratory complex I) to help us carry out aerobic respiration. Aerobic respiration is a good thing because we get way more energy from our glucose than we would otherwise (38 molecules of ATP per 1 molecule of glucose, in fact, as opposed to 2). You've probably seen those 3 dimensional puzzles that require many different pieces to fit together in a certain way. If I took one of those puzzle pieces and damaged it somehow so that the shape changed a little, what do you think would happen to the puzzle? Since the NADH dehydrogenase subunit 5 protein has to interact with so many other parts, we can predict that mutations that change the amino acid sequence of NADH dehydrogenase subunit 5 would probably have harmful effects, and those effects would most likely limit the ability of individuals with these mutations to reproduce. In fact, this is correct. Mutations in this gene are harmful and do cause serious disease (1). References: 1. Nishigaki, Y.; Marti, R.; Hirano, M. : ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy. Hum. Molec. Genet. 13: 91-101, 2004.

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