Hi. In this video, we're going to be talking about spontaneous mutation. So the majority of DNA mutations that occur in organisms are spontaneous. The reason that I can say this is that I know this is true, is because of an experiment done by two scientists, Luria and Delbrück, and they conducted this test called the fluctuation test. They proved that the majority of the organism mutations are just spontaneous. They had two bacterial cultures and tested for their ability to develop resistance to a virus, a bacteriophage. They grew two different bacterial cultures and exposed them to different conditions and asked about resistance to lysis. Remember bacteriophages; they enter, they infect, cause lysis, bursting of that bacteria. They used these bacterial cultures to look for lysis of bacteria, and when they didn't undergo lysis, that would be an example of resistance. They were resisting that infection, resisting that lysis.
How this experiment was designed: they had two cultures, one had 20 individual small cultures, and this was grown in the presence of the phage. The bacteriophage was put into these cultures, and those bacteria were grown while they were exposed to the virus. The second one had one large culture, and this was not grown, so this did not have phage. They wanted to look for resistance. Their hypothesis was that if it's spontaneous, then it wouldn't matter whether the bacteria were grown in the presence of the phage or not because the presence of the phage would have nothing to do with whether a bacteria developed resistance. They tested this after the growth by taking a little bit of each culture and placing it again onto a plate and exposing it again to bacteriophage and looked for lysis. They found that resistance, the ability to resist that infection, resist lysis, was not dependent on previous exposure to the phage. The phage did not induce that mutation. Those mutations just spontaneously occurred.
Their data showed that the small cultures that had the phage had a range of 1 to 107 resistant colonies, where the one that did not have the phage had 14 to 26. These different numbers had nothing to do with the presence of the phage. What this suggests is this column here is induced, so this would be if the phage had some kind of effect on mutation, and this would be spontaneous. Over time, if you have various bacterial plates, if it were indeed induced, then the phage would induce the same number of colonies to resist each time. Whereas, if it was spontaneous, you would see a variety of colony counts such as 1, 4, none, or 2, demonstrating that spontaneous random mutations were occurring regardless of phage presence.
Now, knowing that organisms most of the time undergo spontaneous mutation, what are the different mechanisms that lead to these spontaneous mutations? One potential cause is errors in DNA replication. DNA polymerase is imperfect and makes mistakes, leading to errors such as transitions, transversions, frame shifts, and more. Naturally occurring DNA damage can occur due to environmental factors like UV light from the sun, causing damage like depurination and deamination. Another mechanism is through tautomeric shifts, where different forms of DNA bases (A, T, C, G) differ based on the position of protons, leading to unusual base pairings and potential mutations.
An example of a spontaneous mutation disease in humans includes trinucleotide repeat diseases. These diseases arise from the addition of nucleotide repeats, specifically trinucleotide repeats, which means three. An example from your book is Fragile X Syndrome, where normal individuals have 6 to 54 CGG repeats in a specific gene, but individuals with Fragile X Syndrome may have 200 to 1300 CGG repeats due to the mechanism of strand slippage. During DNA replication or transcription, certain sequences may bind to themselves, creating loops that can lead to multiple readings and the insertion of additional repeats. So, these are just a few of the mechanisms through which spontaneous mutations occur. Let's now move on.
