[Caitlin:] Ah, I see you've been to the farmers' market again. And, of course, you would pick the mutant fruit. [Felicia:] What are you talking about? That banana is perfect! No bumps and no bruises. [Caitlin:] Well, it's a mutant. Think about it. Haven't you ever wondered why bananas don't have any seeds? None. Isn't that a little weird? [Felicia:] Well, now that you've mentioned it... [Caitlin:] It's a mutant! Now, granted, the original mutation happened long ago. We humans decided that we quite liked bananas without seeds. So, we continued to grow this mutant variety. [Felicia:] Well, the banana is in good company because I can think of another mutant in the room. [Caitlin:] I know, I know. The hair. Red hair is also a mutation. [Felicia:] It also explains why you were able to spot the banana so fast. Takes a mutant to know one. [Caitlin:] By the end of this week, we'll have covered everything you ever wanted to know about mutations on DNA Decoded. [Music] [Felicia:] So far in this course, we've talked about DNA replication and what happens when everything goes right. Let's quickly recap how DNA is copied. DNA polymerase gets into position at the start location. As it moves along, the DNA polymerase reads the sequence of base pairs using Watson and Crick Rules: A pairs with T and C pairs with G. DNA polymerase finds the corresponding base and attaches it to form a base pair. Let's say DNA polymerase is in the process of building along this segment of DNA. The correct sequence according to Watson and Crick's rules would be... [Caitlin:] Now, let's talk about how that DNA is transcribed into messenger RNA. The DNA strands are unzipped to create a transcription bubble. RNA polymerase gets into position at the start location and proceeds to add the Watson and Crick base pairs. The end result is a single strand of mRNA. Now, the messenger RNA is read three bases at a time by the ribosome. Those triplets are called codons. There are 64 ways to combine the three bases to create different proteins. We can translate the mRNA codon into the instructions for building amino acids by looking up which codons map onto which amino acids. If we decode the codons from the messenger RNA for the correct DNA template, here's what we would get: M-L-L and N are all the amino acids. But what happens when things go wrong? Errors in DNA replication results in mutations. Some are harmless, some are valuable, some are crippling. [Felicia:] Mutations are just changes in DNA. They are actually more common than you think. You might think all mutations are bad, but there are plenty of cases where a mutation has no consequence at all. Weird, right? That's biochemistry for you. Let's explain. [Caitlin:] There are probably harmless mutations happening inside us right now, as our cells divide and new tissues grow. To understand why some mutations make a difference and others do not, we need to introduce two terms: synonomous and nonsynonymous mutations. Suppose something goes wrong and an A is mistakenly added in to our example of DNA instead of a C. That's a mutation, or a mistake in the copying. It looks bad -- but let's fast forward through the next steps to see what the consequences will be. Which gives us the following RNA sequence... What does this messenger RNA code for? Well, look at that! There was no difference in the amino acid sequence, so there's no difference in the protein created. [Felicia:] More than one triplet can code for the same amino acid. It's like the two codes are synonyms for each other. In this case, both messenger RNA sequences produce the same amino acid: leucine or L. [Caitlin:] Even though there was a mutation in a base pair, the mRNA could still build the correct protein. This is a synonomous mutation. It doesn't alter the amino acid sequence. Now, let's shift gears and look at another mutation. Here, the error is in C at the fourth position. This means the messenger RNA is... What does the mRNA code for? [Felicia:] Yikes. Red alert. Houston, we have a problem. Now, we've got a different amino acid sequence. [Caitlin:] Sure do. That valine does not belong there. This could mean the protein's function is affected. This is called a nonsynonymous mutation because the protein sequence has been altered. Replication mutations are just one kind of mutation. You can find out about other types of mutations in the supplemental materials. [Felicia:] Now, let's go back to the mutation example we mentioned at the beginning of this video. The flaming red hair that makes Cait a mutant. Your red hair is caused by a mutation in your MC1R gene. That stands for melanocortin 1 receptor. This protein plays a key role in determining hair and skin colour. Here's the cool part. The most common mutation relating to red hair is caused by a single nucleotide change. [Caitlin:] Yup, that's right. Just one single nucleotide change can make a big difference. Melanin is the pigment that determines the colour of your eyes, skin and hair. Humans actually produce two types: red and black. The mutation in the MC1R gene in redheads means they produce predominantly red pigment and very little black pigment. There you go: red hair. [Felicia:] As far as mutations go, seedless banana and red hair are pretty harmless. But other types of mutations can have tragic consequences. [Caitlin:] Cystic fibrosis is a genetic disease that results from a single gene mutation on chromosome 7. Individuals that suffer from cystic fibrosis have respiratory and digestive disorders. The most common mutation that leads to cystic fibrosis is a deletion mutation. Three nucleotides are missing meaning that an entire amino acid is lost. Patients with cystic fibrosis have an impaired protein that results in unusually thick mucus production. [Felicia:] So, to recap, sometimes, mistakes happen. Mutations are errors but not all mutations are bad. As we've seen, mistakes are responsible for giving us delicious bananas and for giving Cait her red hair. But sometimes, the mistakes have very serious consequences, as we saw with cystic fibrosis patients. This brings us to our next video topic: Genetically Modified Organisms. Stay tuned.
