Welcome back. We're now into week four, unit 4 of Introduction to Human Behavioral Genetics. And week three and week four are really meant to provide us with the foundation in genetics that we'll need when we want to explore in depth behavioral phenotypes from a genetic perspective. Last week, we really went through quantitative genetics. This week we're going to go through the basics, the very basics of molecular genetics. Now, some of you will already have a background in much of what I'll be talking about this week. And so, you should feel free to skip ahead. But unless you've had a course in, within the last couple of years, please make sure to check-in towards the end of the, of the modules, because I think you'll probably find there's some new material there, that might not have been covered in your previous genetics courses. But probably, for most of us the type of thing I'm going to talk about will be helpful in providing a foundation for us going forward when we begin to look at the phenotypes like schizophrenia, and intelligence, and subsequent links. So this first module is about DNA. We all know about DNA. It's, it's actually become part of the popular culture. The double helical form is actually almost iconic. But let's talk a little bit more in depth about what actually DNA is. So, of course, DNA structure is this familiar double helical form. It's comprised of two sugar phosphate backbones, and the two backbones are connected by hydrogen bonds that form between the bases on the two backbones. And, the bases are such that there's a constrained pairing across the two backbones. The nucleotide base adenine, always pairs with thymine. A pairs with T. The nucleotide base guanine, G, pairs with cytosine, C, on the alternative base. One thing that DNA does, we know that it does, is that when cells divide in mitosis, which we talked about earlier in the course, as well as meiosis, the DNA duplicates itself. The constrained pairing of the nucleotide bases across the two strands of DNA actually provided with the property to self replicate. And this is illustrated in this next slide. The way DNA replicates is actually the double helical form unwinds. And each strand then, can form can serve as a template for the synthesis, synthesis of a complimentary strand. And because we know that G on one strand always goes with C on the alternate strand, or T with A, then one, one strand can fully recover the information you need in the alternative strand. So that how, is how DNA replicates itself. And DNA exists, for the purpose of, of, of the course here, really DNA exists within the nucleus of every cell of our body. There is some DNA outside the nucleus, but for the types of things we're going to talk about the DNA within the nucleus is by far the most important DNA. And DNA is packaged into chromosomes. We could think of chromosomes as very, very, very long strands of DNA packaged along with proteins. We've known for many, many years that a primary function of DNA is to serve as a code for life. To provide a code book for the developing organism. And the way DNA does that is that it codes for proteins. Our bodies are made up of many different types of proteins. Our muscles, our bones, our neurons. Or even the enzymes that we have, that break down food that we ingest. Our coded, our proteins that are coded for by DNA. How does DNA do this, though? We've know that, as I pointed out before, that DNA exists within the nucleus of the cell. But proteins are actually synthesized outside the nucleus, in the cytoplasm of the cell. So, it was recognized very early on that there had to be a multistage process by which DNA would take the information that existed within the nucleus of the cell in the DNA and transport that information out into the cytoplasm, to actually serve as a code book for building a protein. That multistage process has been called by Francis Crick, and Francis Crick was one of the co-discovers of course of the DNA helical structure, by Francis Crick, as the central dogma of molecular biology. There are basically two stages that we're going to focus in on here. First of all DNA, a double-stranded nucleic acid, is first transcribed into another nucleic acid, a single-stranded nucleic acid called RNA, ribonucleic acid. RNA is single-stranded, made up of nucleotide bases just like DNA with one exception. DNA has four nucleotide bases G, C, T, A. In the case of ribonucleic acid, it also has four nucleic acid I'm sorry, nucleotide bases, but U, uracil, substitutes for thymine, T. So the first step in this process is to transcribe DNA into another nucleic acid, RNA. The second stage in the process is then RNA serves as the template for building a protein, and that process is called translation. So the multistage process is DNA is transcribed to RNA, RNA is then translated into a protein. And what proteins are are sequences of amino acid, amino acids, polypeptide chains. So let's take a look at how this would work. Here's a stretch of DNA. And remember, of course, the DNA is two-stranded. And the basis are, the nucleotide basis are constrained across the, paired across the two strands. So A on one strand will always go with T on the other strand. G with C and so on. Now, I'm going to talk about this several times as we go through talking about DNA and genes, but there's actually an orientation to DNA. And the orientation is designated as there's a 5 prime end to the DNA molecule and a 3 prime end. We don't need to really get hung up on exactly what 5 prime and 3 prime mean, it has to do with the, the orientation of the carbon molecules. What's really important for us is that there is an orientation a way to read the DNA. There's two strands here, one oriented 5 prime to 3 prime. The complementary strand, oriented 3 prime to 5 prime. Now the terminology, initially, I think, is going to seem a little confusing. But I think if you stick with it, you'll understand it. One strand, is called the sense strand. The other strand is called the antisense strand. In any region of the genome, only one of the strands would be transcribed, into RNA. The antisense strand is actually the template for the transcription into RNA. Now, if it's the template for the transcription into RNA, why is it called the antisense strand? It's called, the reason that this strand is called the sense strand is because this strand looks like the resulting RNA except wherever there's a T in this strand, a U is substituted here. So even though this is the template for synthesising the RNA. It's the other strand that's called the sense strand because that's what the RNA molecule will look like. When we have A here, we're going to have A here; G here, we'll have G here. Of course, T in DNA is replaced with U in RNA. Only one of the strands will be transcribed and we'll get back a little bit later to, well. What is it about that strand which actually leads it to be transcribed? How does it, how does the transcription machinery know it should be transcribing one strand and not the other? Well, we'll come back to that. The second step then is to take RNA as a template for the synthesis of a protein. How does that happen? The basic informational, informational unit in the genome is 3 nucleotide bases, and the term for that is called a codon. If there are four nucleotides, then there are 4 times 4 times 4 or 64 possible combinations of the three letter bases. But there are actually only 20 possible amino acids. So there's a lot of redundancy in the system. But of course, if, if you tried to code for 20 amino acids with two nucleotide bases, it wouldn't be enough. You get 4 times 4 is 16. So you need at least 3 to cover 20. But of course, you have many more than 20. You've probably seen this before, it's usually specified in terms of the RNA code, but this is the universal genetic code. This is how the three basis of RNA is translated into amino acid. So that UUU in RNA codes for the amino acid that we talked about a little bit earlier in the first week of the course. That's the amino acid phenylalanine or UUA, leucine, so on and so forth. So back to our little example here. RNA then would actually code for, the first three bases would code for amino acid called methionine. The next three for a second called cysteine, leucine, valine, and so on and so forth. It turns out that methionine is actually the beginning of all of these polypeptide or amino acid strings. So this is always the initial amino acids. Is it not necessarily the initial amino acid in every protein, it might get sniped out later but it, in terms of transcription and then subsequently translation this is always the start code. This particular sequence, here and then, there are other codes that tell the translation machinery and the, and the transcription machinery to stop. These are these codes up here. So that's a little introduction to DNA, RNA and its basic biological function. Next time, we'll talk about what a gene is. [BLANK_AUDIO]
