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MICHAEL HEMANN: We have a pretty diverse group of people.
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So we're just going to start with a little bit
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of a refresher on some basics before we
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get into the genetics in subsequent lectures.
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So essentially the central dogma of biology
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is that we have DNA that goes to RNA that goes to protein.
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This is just the basic tenets of modern molecular biology.
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So DNA is copied in a process called DNA replication.
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DNA replication is essentially the polymerization
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of new DNA molecules templated by existing molecules.
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So if we just look at a short stretch of DNA here,
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a four-base sequence, We have a 5 prime phosphate,
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we have a 3 prime hydroxyl, we have two copies of this DNA.
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So we have the complementary strand here.
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And this is replicated into two daughter molecules of DNA
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based on a process called semi-conservative replication,
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which means that each of these strands
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actually templates the addition of nucleotides
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to the other strand.
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So we have these two molecules that come apart,
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and you have the synthesis of new strands
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from 5 prime to 3 prime in both of the daughter strands.
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So from the big-picture perspective,
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we have a long sequence of DNA.
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And we have the synthesis from 5 prime to 3 prime
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on both strands.
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One strand, you basically have continual synthesis
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from lots of origins or replication,
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and the other you have Okazaki fragments.
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So again, a semi-conservative strategy
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that leads to the production of two progeny molecules of DNA,
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half of which are the old DNA and half of which
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are newly synthesized from nucleotides that
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are sort of swimming around.
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So the second process is this process of DNA to RNA.
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So transcription occurs off of a DNA template.
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where we have the binding of an RNA polymerase
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to a transcriptional start site, and you
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have the new synthesis of an RNA that is essentially
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a copy of this top strand--
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this synth strand-- from a migrating transcriptional
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bubble.
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So this is early in transcription, and this is late
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in transcription.
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where we have the production of a long RNA molecule that,
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again, is templated off this lower strand.
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It's identical to the top strand, of course.
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It's RNA and not DNA.
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So it's a different molecule--
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less stable molecule-- that essentially is
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the active copy of our genome.
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So it's actively producing information
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that's used to encode proteins.
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And so that synthesis of proteins--
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so going from RNA to protein is called translation.
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So not all RNAs are translated.
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So you have lots of classes of RNAs
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like tRNAs and ribosomal RNAs that aren't translated.
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You have small RNAs that serve to regulate transcription,
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like microRNAs.
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But all proteins are encoded through the translation
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of mRNAs.
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And so you have a ribosome, you have an mRNA,
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and then you have addition of amino acids
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to a growing polypeptide through the introduction
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of tRNA-loaded individual amino acids.
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So the step wide addition of amino acids
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to a polypeptide chain leads to the production
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of a large polypeptide.
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This large polypeptide is folded into a diverse class
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of proteins in the cell--
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proteins including enzymes and receptors
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and structural proteins and hormones and lots
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of different classes of proteins,
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essentially, all made during this process.
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And so again, the central dogma of molecular biology
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and genetics is that you have a gene which
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is a double stranded piece of DNA that yields an RNA that
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is a smaller sequence from a transcriptional start site down
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to a polyadenylation site.
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And this encodes for the translation of a protein
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from the start codon like AUG--
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and there are some degenerate start codons--
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but mostly AUG.
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So this is the basic principle.
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This is the gene as a structural entity.
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So a typical gene in our cells--
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average gene is around one to two kilobases,
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so 1,000 to 2,000 bases.
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That corresponds with a triplet code to 300 to 600,
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or 333 to 666 amino acids.
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There are genes that are much larger.
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So dystrophin, for example, is a gene
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that is two million base pairs.
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This is the gene that is altered in the condition Duchenne's
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muscular dystrophy.
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It's mostly introns, which we'll talk about.
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But in total physical length, it is two million bases.
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Genes can be very small.
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They can be 30 or 40 amino acids.
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And sometimes it's actually very difficult actually to predict
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whether something is a protein-coding gene or not--
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and we'll talk about that--
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how do we know what a gene is, how do we assess
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whether it's protein coding.
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When we say that we actually have
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a certain number of genes in the genome,
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how and why are we saying that?
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How can we possibly predict that?
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E. coli has around 4,000 genes.
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We are at the other end of the spectrum.
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So humans have 20,000 to 25,000 genes.
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Actually, this number has evolved over time.
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Initially, but prior to the human genome sequence,
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it was thought that there were about 100,000 genes,
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but we're simpler than we thought.
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But there are much more simple organisms.
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For example, an organism with the perhaps unfortunate name
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Mycoplasma genitalium has the fewest genes of any organism.
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It's 467 genes, so that's basically the bare bones.
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That's what you need to get by in the world, around 467 genes.
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Anybody know what organism has the most genes?
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Any guesses?
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So plants have the biggest genomes
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in terms of overall sequence length.
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There is a kind of flea that used to be the big winner.
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So there was a flea that had 31,000.
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But right now, it's the octopus, 33,000 genes.
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They have all these weird N-cadherins
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that are involved in their distributive neural network.
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It's a really cool kind of thing.
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But they have more than we do.
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