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Mendelian Genetics & Foundational Experiments

    Long, 4 examples, 5 practice questions

  • Gregor Mendel is known as “The Father of Modern Genetics”.
  • Punnett squares can be used to track the Mendelian inheritance of genotypes and phenotypes of future generations.
  • Rosalind Franklin, and James Watson and Francis Crick are responsible for the discovery of DNA as the genetic material of the cell.
  • Genes are found on chromosomes.
  • The central dogma of molecular biology is as follows: DNA→RNA→Protein

Mendelian Genetics & Foundational Experiments

Who is known as the “father of Modern Genetics”?
  • James Watson
  • Francis Crick
  • Gregor Mendel
  • Rosalind Franklin
Who identified the “transforming principle” in 1928?
  • Frederick Griffith
  • Beadle and tatum
  • Erwin Chargaff
  • Sydney Brenner
What substance was proven to be the genetic material of the cell in the late 1950s?
  • RNA
  • DNA
  • Protein
  • Lipid
What is the central dogma of molecular biology?
  • DNA to RNA
  • RNA to Protein
  • DNA to Protein
  • DNA to RNA to Protein
What triplet codon was used to crack the first amino acid of the genetic code?
  • UUU
  • TTT
  • CAG
  • GGG

*These practice questions are only helpful when you work on them offline on a piece of paper and then use the solution steps function to check your answer.


Mendelian Genetics & Foundational Experiments

Lecture Slides are screen-captured images of important points in the lecture. Students can download and print out these lecture slide images to do practice problems as well as take notes while watching the lecture.

  1. Intro
    • Lesson Overview
      • Gregor Johann Mendel
      • Mendel’s Laws
      • Principle of Independent Segregation (of Alleles)
      • Example 1
        • Principle of Independent Segregation (of Alleles)
        • Example 2
          • The Chromosomal Theory of Inheritance
          • Gene Linkage
          • Genes are Found on Chromosomes
          • Example 3
            • Discovery of the Genetic Material of the Cell
            • Example 4
              • Discovery of the Genetic Material of the Cell
              • Discovery of RNA
              • The Central Dogma of Molecular Biology
              • Cracking the Genetic Code
              • Intro 0:00
              • Lesson Overview 0:22
              • Gregor Johann Mendel 1:01
                • Was a Biologist and Botanist
                • Published Seminal Paper on Hybridization and Inheritance in the Pea Plant
                • Results Criticized
                • Father of Modern Genetics
              • Mendel’s Laws 2:19
                • 1st Law: Principle of Independent Segregation of Alleles
                • 2nd Law: Principle of Independent Assortment of Genes
              • Principle of Independent Segregation (of Alleles) 2:41
                • True Breeding Lines / Homozygous
                • Individuals Phenotypes Determined by Genes
                • Alleles
                • Alleles Can Be Dominant or Recessive
                • Genotypes Can be Experimentally Determined by Mating and Analyzing the Progeny
                • Individual Alleles Segregate Independently Into Gametes
              • Example 1 6:18
              • Principle of Independent Segregation (of Alleles) 16:11
                • Individual Genes Sort Independently Into Gametes
                • Each Gamete Receives One Allele of Each Gene: 50/50 Chance
                • Genes Act Independently to Determine Unrelated Phenotypes
                • Example: Punnett Square
              • Example 2 21:36
              • The Chromosomal Theory of Inheritance 30:41
                • Walter S Sutton Linked Cytological Studies with Mendels Work
                • Diploid Cells Have Two Morphologically Similar Sets of Chromosomes and Each Haploid Gamete Receives One Set
                • Genes Are on Chromosome
                • Gene for Seed Color’s on a Different Chromosome Than Gene for Seed Texture
              • Gene Linkage 31:55
                • Mendel’s 2nd Law
                • Genes Said to Be Linked To Each Other
                • Linkage Between Genes
                • Linkage is Never 100% Complete
              • Genes are Found on Chromosomes 33:00
                • Thomas Hunt Morgan and Drosophila Melanogaster
                • Mutation Linked to X Chromosome
                • Linkage of White Gene
                • Eye Color of Progeny Depended on Sex of Parent
                • Y Chromosome Does Not Carry Copy of White Gene
                • X Linked Genes, Allele is Expressed in Males
                • Example
              • Example 3 35:52
              • Discovery of the Genetic Material of the Cell 41:52
                • Transforming Principle
                • Experiment with Streptococcus Pneumoniae
                • Beadle and Tatum Proposed Genes Direct the Synthesis of Enzymes
                • One Gene One Enzyme Hypothesis
                • One Gene One Polypeptide Theory
                • Showing the Transforming Material was DNA
                • Did This by Fractionating Heat-Killed “S” Strains into DNA, RNA, and Protein
                • Result: Only the DNA Fraction Could Transform
                • Leven: Tetranucleotide Hypothesis
                • Chargaff Showed This Was Not the Case
                • Chargaff: DNA of Different Species Have Different Nucleotide Composition
                • Hershey and Chase: DNA is the Genetic Material
                • Incorporate Sulfur into Protein and Phosphorous into DNA
                • Results: Phosphorase Entered Bacteria and Progeny Phage, But no Sulfur
                • Rosalind Franklin’s “Photo 51” Showing the Diffraction Pattern of DNA
                • Watson and Crick: Double Helical Structure of DNA
              • Example 4 56:56
              • Discovery of the Genetic Material of the Cell 58:09
                • Kornberg: DNA Polymerase I
                • Three Postulated Methods of DNA Replication
                • Meselson and Stahl: DNA Replication is Semi-Conservative
                • How DNA Was Made Denser
              • Discovery of RNA 1:03:32
                • Ribosomal RNA
                • Transfer RNA
                • Messenger RNA
              • The Central Dogma of Molecular Biology 1:04:49
                • DNA and Replication
                • DNA and Transcription = RNA
                • RNA and Translation = Protein
                • Reverse Transcription
              • Cracking the Genetic Code 1:06:58
                • What is the Genetic Code?
                • Nirenberg Discovered the First DNA Triplet That Would Make an Amino Acid
                • Code Finished in 1966 and There Are 64 Possibilities or Triplet Repeats/ Codons
                • Degeneracy of the Code

              Transcription: Mendelian Genetics & Foundational Experiments

              Hello, and welcome back to

              Today, we are going to talk about Mendelian genetics and foundational experiments in molecular biology.0003

              This is going to be an interesting unit because we are talking mostly about the history of how we started with Gregor Johann Mendel.0009

              We are going to go all the way up until we are somewhere in the 20th century, at least.0023

              We have to start any talk about molecular biology by starting off with Gregor Mendel.0031

              We will then go through chromosomal theory of inheritance.0039

              A large chunk of this talk is going to be on the discovery of the genetic material of the cell which we now know is DNA.0043

              We will talk briefly on the discovery of RNA and we will mention how the genetic code was cracked.0052

              As I said, talking about molecular biology cannot be done without first started talking on Gregor Johann Mendel.0061

              Gregor Mendel within the 19th century, at the time he was considered a biologist and a botanist.0071

              He did most of his work on plants.0078

              He published his similar paper in 1866, hybridization and inheritance of the pea plant.0080

              Unfortunately for Mendel, his results were criticized at the time of publication, 0090

              as only being about hybridization and not being about inheritance.0095

              Unfortunately for him, he was not given the respect that he deserved in his time 0100

              because his results were not widely accepted until after he passed away.0106

              That happened in about 1900’s, that is when his work was picked back up by other scientists.0110

              However, looking back after the fact now, we consider Gregor Johann Mendel as the father of modern genetics.0116

              He did all of this work while being an Augustinian follower, he was a monk.0126

              This was his research that he did on the side.0133

              Let us talk about Gregor Mendel’s laws.0137

              He made two very important laws, based off of his research.0141

              This is what he postulated, he showed that there is a principle of independent segregation.0146

              We are talking about alleles.0152

              His second law is the principle of independent assortment, speaking toward genes.0154

              His first law, he started with true breeding lines for certain observable traits, he used his pea plant.0163

              What a true breeding line means is that they are homozygous.0172

              They always produce the same phenotypes.0177

              If it is a green pea, then when you mate two green peas together, you get only green peas.0182

              He referred that an individual’s phenotypes was determined by a pair of unit factors.0195

              We call those nowadays, we call unit factors, we call these genes.0202

              He said different versions of a single gene are called alleles.0214

              They can vary just slightly, maybe even as small as a single nucleotide different, in an entire many thousand base pair gene.0219

              He said that alleles can be dominate or recessive.0230

              What that means is that any recessive gene, for example, if we say that green is dominant but it can also be yellow.0234

              Green, if these are the two alleles, anything, if green is dominant, the only thing that two dominant alleles, big g’s, will be green.0250

              Anything with even one dominant allele, the big G will be green.0271

              Only something with two recessive alleles will be a different phenotype.0281

              In this case, let us say it is a red.0292

              Your observable phenotype which is this, is what is called a phenotype.0300

              Your genetic composition which is this stuff, that would be your genotype.0316

              Genotypes can be experimentally determined by mating and then analyzing the progeny.0338

              You analyze the phenotypes, the progeny.0347

              Remember, phenotype is the innate thing you can see, genotypes is the actual genetic makeup.0349

              Individual alleles, he says (Mendel), would segregate independently into gametes or sex cells, like sperm and eggs.0355

              With each gamete receiving one allele from each pair, one allele from each pair of alleles.0365

              Using a Punnett square, draw out all our possible genotypes and 0380

              phenotypes of a cross between true breeding white flowers and true breeding purple flowers, with purple being the dominant.0386

              Proceed through the F2 generation.0398

              First of all, we need to now what all these means.0401

              First of all, a Punnett square is a way to visualize those mating.0405

              An F2 generation is what is called the filial 2 generation.0412

              You start with your parents here, mom and dad.0416

              They cross and produce, let us say you and your sister.0427

              Right here, let us say you have a baby of your own.0438

              When you meet your, for my example, let us say a wife, together you produce a baby.0445

              This is what is consider the parental generation.0465

              This is the filial, 1st filial generation or F1, this is the F2 generation.0471

              Proceed through there using a Punnett square.0478

              Remember, our Punnett square would be looking like an actual square, based on all of the genotypes that we get for a specific gene.0480

              Let us try this solution.0490

              What was dominant, if purple is dominant, let us write that there.0501

              Before we start on this, let us go back to Mendel.0511

              He mated plants, he mated pea plants.0519

              He looked at their seed coat and seed color.0524

              If we do an example of Mendel’s seed color or seed coat, then maybe we will be able to understand how to do the flowers.0527

              He had true breeding lines, meaning they are homozygous.0538

              He took true breeding round seeds and true breeding wrinkled seeds.0541

              The round seeds are R, the wrinkled seeds are r and r.0551

              This is parental.0559

              When you mate them, you get all R and r.0566

              Remember, if round at this point is dominant, all of these will be round.0573

              Now what you are going to do, you mate the F1 generation to itself.0581

              It is going to be another R and r.0589

              What you can do, these are going to be all the gametes possible.0594

              If these are the female gametes, these are the male gametes, you can make a Punnett square.0609

              Our Punnett square is going to look as such.0625

              You are going to have your female gametes.0630

              All you have to do is fill in the box across from each other.0643

              This one, we have a r crossing with a R, this is R and r.0648

              These are two R, this right here is a R and r.0657

              This right here is two r.0664

              In this case, when we end this, by the way, is our F2 generation.0668

              In this case, what we have here, remember dominant is round.0675

              We have this is round, this is round, this is round, and here is our wrinkled one.0678

              As we see here, we have a 3 to 1 ratio of dominant to recessive for phenotype.0687

              We have two different phenotypes but we have three different genotypes because we have two of these.0706

              Maybe this will help us get our flower one better.0729

              Do you want to try?0733

              Let us go ahead and give this a try.0735

              We have our purple and we have our white.0739

              We normally call our genes for the dominant.0742

              We will call our purple P and P, we will call our white p and p.0746

              This is purple.0759

              When they mate, what do we get?0765

              We get P and p.0771

              That is still going to be what color, purple.0773

              This is our F1.0780

              What do we have to do, we need to mate this to another P and P.0786

              What are our options, we have our p, P, P, p.0793

              Let us say this is the mom and this is the dad.0807

              If we follow this out, we can make our nice Punnett square with P and P, Pp, our P and P.0816

              We have Pp, we have Pp, p and p.0834

              What do we have here, we have this being purple, this being purple, this being purple.0842

              This one is our lone white.0850

              Just the same as this, we have a 3 to 1, in favor of purple for phenotype.0854

              We have 3 different genotypes, PP, Pp, pp.0867

              Remember we have two of these.0878

              Hopefully, we found that helpful.0881

              What is very important is that, as I have said before, we always find the phenotype of the heterozygote, 0889

              or the phenotype of the dominant allele, being seen in the heterozygote, these ones.0896

              We are seeing the dominant phenotype in those, in heterozygote.0904

              For many alleles, this does not always happen.0913

              We do not necessarily have to have alleles that are completely dominant or completely recessive.0919

              Then, we got really lucky in the fact his pea plants were true breeding lines in his way and 0924

              they were either dominant or recessive alleles.0931

              Sometimes you can have something called incomplete dominance or co-dominant.0933

              That is where, let us say, for example, you had a red flower and a white flower, and you mated those.0937

              Let us say if red was dominant, instead of getting 3 red flowers and 1 white flower in the F2 generation, 0945

              you might get your dominant ones being red, your recessive homozygous ones being white, 0954

              but your heterozygous ones maybe a shade of pink.0961

              That would be what is called incomplete dominance.0965

              Mendel’s principle of independent segregation, he is talking about the alleles.0974

              Individual genes will sort independently into a gamete.0980

              Individual genes, let us say if your gene 1 and gene 2, do not necessarily always have to go into the same sperm or same egg.0985

              They can go into different ones.1002

              Each gamete receives one allele of each gene with a 50-50 chance.1005

              We can use Punnett squares again, to visualize the possible genotypes and phenotypes.1012

              What we can see is that, we see that genes will act independently to determine unrelated phenotypes.1018

              This is important because we can have multiple genes making a single phenotype, that complicate things even more.1026

              Here is an example that of a cat that is being mated with another cat.1037

              What we see here is, what is dominant is having a short tail.1044

              Short tail is dominant, that is why it is S and brown is dominant.1053

              When you are looking at multiple genes, we are looking out here at two genes, it is the coat color and tail length.1060

              Each of these genes has a different allele.1081

              It can be for coat color, you can be white or brown.1084

              For tail length, it can be short or long.1095

              Remember this is parental.1103

              When you mate true breeding, meaning homozygous parental generation, you are going to get all heterozygote.1107

              All your heterozygote, remember are going to have the phenotype of the dominant allele.1119

              The dominant allele, the dominant allele for coat color is brown and the dominant allele for tail length is short.1126

              What we see here is that all of our F2 generation, all 4 are brown and have short tails.1149

              You would mate this F1 generation to each other to produce your F2 genes, right, your F2 offspring.1170

              What we see here is that we are no longer looking at our 3 to 1 ratios because now we have two genes involved.1182

              We have 16 different possibilities.1189

              What do we end up seeing?1192

              We see a 9 to 3 to 3 to 1 ratio in the F2 generation.1194

              What is it, it is going to be 9 in the double dominant.1203

              9 are going to be brown and have short tails.1210

              These next 3 are going to be the heterozygous looking ones, 1224

              to where you are going to be dominant in one thing and recessive in another trait.1228

              3 are going to be brown with long tails.1232

              We have another separated group, the heterozygous group, because we are independent segregation of these.1241

              We are going to have 3 that are white and short.1248

              And then, you are going to have one that is recessive for both traits and that is going to be white and long.1255

              If we find that one, here is the white and long.1269

              This is how we are going to be able to determine any of our true breeding lines, when we are looking at two different genes.1277

              We are always going to see this 9 to 3 to 3 to 1 ratio.1285

              For an example, let us try this again.1298

              Using the Punnett square, draw out all possible genotypes and phenotypes of a cross between white flowers with long stems1300

              and red flowers with short stems, with white flowers in short stems both being dominant.1310

              Proceed all the way through the F2 generation.1318

              White flowers in short stems are dominant.1321

              We have a cross between white flowers with long stems and red flowers with short stems.1328

              Let us write out what are our parents, what are the parents looks like?1337

              We need one that is white, let us give them the W, we need it also to have long stems.1343

              Let us give them the s.1353

              Now we need one that is red, that is the w.1357

              We need one on the short stems, it is a S.1361

              This is white and long.1365

              This is red and short.1374

              If we mate these, what are we going to get?1380

              We are going to get the full heterozygote.1385

              We are going to get, here are our gametes.1389

              I will just write that out so we can see it.1394

              Gametes are only W and s, this is only w and S.1397

              These crossed are going to give us only this, this is our F1.1404

              What is that, what is this going to be, what is dominant?1427

              White is dominant, white dominant short.1432

              All of these are going to be white with short stems.1434

              What are our possible gametes here?1444

              It is going to be WS, ws, Ws, and ws.1454

              Now, we are going to be able to figure out how to breakdown our Punnett square.1470

              Here is going to be our F2.1478

              We draw these out, this is going to be the same for both maternal and paternal.1482

              Let us draw them out.1487

              We have WS right there, WS over there, Ws.1489

              Let us go through and figure all these out.1556

              This is going to be WW and SS, that is the easy one and this is the easy one too, right.1557

              Two w and two s, those are easy ones.1567

              We just have to fill them in.1570

              This is Ww Ss, this is Ww SS, WW Ss.1572

              This is WW Ss, Ww SS, Ww Ss.1578

              This is WW ss, this is Ww Ss.1590

              This is ww SS, this is Ww Ss, this is Ww ss.1616

              Over here, Ww ss, ww Ss.1650

              Over here, ww Ss.1662

              If we want to look and see, and prove to ourselves that this is in fact in a 9 to 3 to 3 to 1 ratio, 1671

              let us pick out the simple one first.1684

              Here is our single one that has homozygous recessive for both, that is R1.1689

              Let us find the 3 that have dominant one and recessive in the other, and the vice versa.1699

              Over here, let us see.1711

              We have green for this.1715

              We will say this is dominant one not in the other.1721

              Dominant one not in the other.1727

              Dominant one not in the other.1729

              This one is red and short.1730

              This one was red and short.1741

              What about this one?1759

              We are looking for the ones that are white. 1767

              We want to see the ones that are white.1771

              Let us see here, we have white and long, and white and long.1775

              These are white and long.1788

              The other 9 are going to be the ones that are left.1793

              Those are going to be the white and short.1803

              Can we find those, 1, 2, 3, 4, 5, 6, 7, 8, 9.1812

              Each of these 9 have both a dominant allele for white, at least one for white and for short.1822

              Let us go on to the next.1839

              As I said before, Mendel was not appreciated in his own time.1844

              The only reason that he is now appreciate is because other scientists picked up his work 1851

              and gave him credit for doing the initial work.1857

              In 1903, this is about 20 years after Mendel died,1862

              the American biologist Walter S. Sutton linked cytological studies with Mendel’s previous work.1866

              This researcher Sutton emphasized the importance that diploid cells have two morphologically similar sets of chromosomes.1875

              Each haploid gamete, received a single set.1886

              He stated that genes are found on chromosomes with one allele on each homologous chromosome.1891

              We are going to get more further into this as we move into the course.1898

              To explain Mendel’s work, Sutton stated that the gene for seed color 1904

              was on a different chromosome than the gene for seed texture.1910

              Mendel’s second law states that genes should assort independently.1917

              But as Sutton was noticing, many genes did not behave that way.1926

              These genes were said to be linked to each other.1932

              What that means is that these two genes do not sort up independently at a normal 50 to 50 ratio.1936

              They are more often seen together than they are separated.1945

              Linkage occurs between genes because the genes are located within close proximity to each other1950

              and usually on the same chromosome.1958

              Linkage is never 100% complete and that is due to the fact that you can have crossing over in meiosis, in late prophase 1.1962

              Linkage can be above the normal 50-50 which would be considered an unlinked gene.1973

              Seven years later, American biologist Thomas Hunt Morgan and his colleagues1983

              found a mutation in the eye color for drosophila melanogaster.1989

              This mutation was linked to the X chromosome; flies also have X and Y chromosomes.1994

              The linkage of the white gene to the chromosomes is strongly supported 2002

              Sutton's chromosomal theory of inheritance, proposed just 7 years earlier.2007

              Linkage to the sex chromosome was really apparent 2016

              because the eye color of the progeny depended on the sex of the white eyed parent.2019

              The Y chromosome does not carry or copy the white gene at all.2025

              No white gene on the Y chromosome.2029

              For X linked genes, the allele is expressed phenotypically by males.2036

              Regardless of whether it is dominant or recessive because it is the only copy.2041

              An example here, we have this being the female, this being the male.2050

              The male is white eyed, the female is what we call wild type meaning it is normal, what we see in nature.2062

              What we are seeing here is, we have a white wild type female, a white eyed male.2073

              We have the F1 generation, this is parental.2082

              The F1 generation both females, these are males.2089

              Both females and males are wild type, regular brick red eyes is what they call them.2095

              In the F2 generation, these guys are going to be mated to each other.2105

              In the F2 generation, what we see is we get, this is a male, this is a male, and these are two females.2110

              What we end up seeing is, we get 3 that have the brick red wild type eyes and 1 that has white eyes, and it is a male.2120

              When the parent is, with the white eyes is a male, in the F2 generation, 2137

              the one that gets the white eyes is also going to be a male.2147

              The mutation for white eyes, we noticed, when wild type is red and 2155

              we know that the mutation arose spontaneously but very infrequently.2159

              What is important is that we know that males which are just like in humans, XY is a male and female is XX.2164

              Males always donate their Y to any son and they always donate their X to any daughter.2185

              We know that sons always receive their X from their mom, this is important.2205

              Using this information, let us find out what the F1 and F2 generations would look like, 2217

              if the original parents were white eyed female and a wild type male.2224

              The opposite of what we saw before.2229

              Let us draw out our parental.2234

              We have a female that is white eyed, we are going to call the ww.2241

              Then we have a male that is a red eyed, W.2250

              Instead of putting another W there, the Y chromosome does not have the gene for white on it, 2255

              we are just going to put Y for Y chromosome.2261

              When they mate, they are going to produce the F1 generation which is what, what can we get?2265

              We are only going to get, it is different now.2279

              We now, the whole X and Y.2286

              All of the females will get the X from their father, they get a big Y, this is going to be a red eyed.2291

              Let us make this clear, this is red eye and this is white eyed.2307

              The female is going to only be able to inherit that, right.2320

              They will be able to get one of these from their mom.2332

              Any males will be like this.2339

              What we see here is that the females in the F1 generation will all be wild type which is red.2358

              The males will all be mutant which is white.2369

              If we mate these two together, what are our options?2376

              What we can see here is that we have two boys, two girls, or two females and two males.2412

              What do we see, let us look at this one.2422

              What is this one going to be? Ww.2426

              First of all, we know it does not have a Y, it is going to be a female.2431

              We see that it does not have a W, this is going to be white.2434

              Let us look at this one, it is w and Y, we know it is a male.2445

              We know it does not have a W, it is also going to be white.2454

              When we look at this one, Ww, we know it does not have Y, it is a female.2463

              We have a W, it is wild type or red eyed.2472

              The last one here, WY, it got a Y so we know it is a male and we have a W, therefore it is also red.2476

              That is what we see here, we get two white eyed and two red.2489

              But we get both a white female and a white eyed male.2493

              We can start moving closer and closer to current time.2507

              Now, we are in the 20th century, 15 years or so, after we are able to go through the chromosomal theory of inheritance, 2511

              we can move on to thinking about how we can discover or how we discovered the genetic material of the cell.2526

              To preface this, at the time, scientists believe that the genetic material of the cell were proteins.2534

              They did not think that it was DNA, because at the time, the proposed structure of DNA did not lend itself toward replication.2542

              They thought that protein was definitely the genetic material of the cell because it had instamatic activity.2556

              In 1928, we have British bacteriologist Frederick Griffith, 2563

              identifying what he termed the transforming principle, the genetic material of the cell.2568

              He developed this extremely and genius experiment that took this substance that is in a virulent streptococcus pneumoniae, 2575

              bacteria, he was able to transform the non-virulent strain of this bacteria into a virulent strain.2585

              Virulent means is able to cause a disease.2596

              How he did this was, he took the non-virulent strain or the R strain, it was rough looking when it was plated out on Petri dishes.2598

              He injected it in a mouse, he took the blood of the mouse and there were no live bacteria.2610

              The mouse was perfectly fine and alive.2620

              He took this smooth strain, the S strain, because it looks smooth and have this extra protein capsule on it.2623

              This was virulent, he injected into the mice, the mouse, all the mice died.2630

              He was able to extract from the blood live streptococcus pneumonia.2638

              In his next experiment, he heat killed this virulent strain.2645

              He killed the bacteria, kind of just like we do with vaccines today.2649

              He killed it but still injected into the mouse.2655

              The mouse lived and he was not able to pull any live bacteria out of it.2659

              This is the most important step right here.2663

              He took live R strain which is not virulent and he took heat killed or dead S strain.2670

              He mixed those together, injected into the mouse.2684

              What did he find?2687

              He found that the mouse died and he found that he can recover live S strain.2690

              He said, this has got to be the genetic material of the cell, this transforming principle that somehow was able to transform R and S.2699

              But what was that, we do not know.2711

              Fast forward a little longer, this is on the side before we jump back into the big picture.2717

              In 1941, we have Beadle and Tatum proposing that genes throughout the synthesis of enzymes.2724

              They did this by irradiating spores on blood mold.2730

              They found that these were unable to grow on media without argenine which is amino acid.2734

              This amino acid was produced just by a single enzyme.2740

              They came up with this hypothesis that one gene makes this one enzyme, one gene one enzyme hypothesis.2744

              What I want us to understand is that, this has later been amended to be a one gene one polypeptide theory 2753

              because we can make more than one enzyme from a single gene.2761

              That can be done by alternative splicing that we are going to talk about much later in this course.2765

              That was kind of in the side, now we jump back to the main story.2771

              In 1944, now we have Maclyn McCarty at the Rockefeller institute, showing what a transforming principle was and they say that it is DNA. 2776

              How do they do this, they took this heat-killed S strain.2792

              They fractionated it into DNA, RNA, and protein.2795

              Each fraction was tested for their ability to transform the R strain into the S strain.2811

              What they did was they separated each fraction and only gave the DNA from the S strain to the R strain.2819

              They would do another sample where there is only the RNA from the S strain to the R.2827

              Only the protein from the S to the R, separately.2831

              What they found is that the only DNA fraction that could transform an R strain to an S strain was the DNA.2835

              The RNA and the protein fraction did not.2844

              However, this was still not widely accepted because as I said earlier, at the time, 2853

              DNA structure that was proposed by Phoebus Leven was not something that can be applied2860

              to be able to transfer information, it would be replicated.2869

              This is the reason why proteins were thought to be the genetic material.2875

              Phoebus Leven, much earlier, in 1910, he proposed what is called the tetranucleotide hypothesis.2880

              He predicted that the structure of DNA was planar.2889

              An equal quantity of each nucleotides were in each plane.2892

              It looked like this down here, we had a guanine and a cytosine, a thymine and adenine, in each plane.2897

              They look like squares and they added one on top of each other, so on and so forth.2904

              With the phosphate backbone in the middle and the bases on the outside.2909

              Luckily, due to this planar prediction, where we had equal, all four in the same plane all the way up, 2922

              we had another researcher named Chargaff showed that this was not the case.2937

              In 1949, we have an Austrian chemist Erwin Chargaff proposing that DNA of different species have different nucleotide composition.2943

              It always follows this rule, the amounts of adenines always equal the amount of thymines.2955

              The amounts of guanines always equal the amount of the cytosines.2962

              The amount of A’s and G’s always equal the amount of C’s the T’s.2967

              Importantly, A and T ratio, A + T does not have to equal G + C.2972

              They can be varying between different species.2982

              This is important and this is something that we know nowadays. We know that A base pairs with T and G base pairs with C.2985

              Therefore, this makes a lot of sense.2994

              At the time, nobody knew this.2998

              Back to discovering the genetic material of the cell, a few years after Chargaff, gave the light toward the end of the tunnel.3002

              We have the scientists named Hershey and Chase, this American bacteriologist, 3016

              a geneticists, conclusively demonstrating that DNA is the genetic material.3021

              They did this in a really cool experiment. They took bacteriophage.3029

              Bacteriophage is a type of virus that infects bacteria.3035

              The bacteriophage is very simple, all it is consisted of is DNA that is inside the head and the rest of it is all protein.3044

              The head, the coat, the tail, all these stuff is protein, only what is inside the head is DNA.3060

              What Hershey and Chase did is they took radioactive isotopes of sulfur and phosphorus,3070

              incorporated them into the growing bacteriophages.3076

              You can specifically incorporate sulfur into protein.3081

              Meaning, the sulfur was only going to be in the protein coat, on the outside.3091

              They also took the phosphorus, this isotope, that could be specifically incorporated into DNA, 3100

              meaning it is only inside that group on that DNA.3107

              What they did was, after growing the bacteriophages in these isotopes, they were allowed to affect the bacteria.3112

              As we see here, we have two different types.3123

              Ones that were just labeled with the sulfur, only the proteins.3127

              Ones that were just labeled with the phosphorus, only the DNA.3140

              What they see is, you let them infect.3145

              They latch onto the bacteria and shoot their DNA into the bacteria.3147

              The whole point they want to do is make new viruses and breakout.3153

              They were allowed to infect the bacteria and then, they were thrown literally into this blender3158

              It is like a blender you have on your counter.3165

              It is actually still held at Cold Spring Harbor, in New York, the original blender that Hershey and Chase performed this experiment with.3168

              They threw everything into this blender, heat blend, that basically shakes the bacteria off of everything.3176

              It breaks everything open, it shakes the phages to everything.3186

              What they found is that the phosphorus, which we know is associated with DNA, was found into the bacteria.3191

              As well as the progeny phage but the S35, the sulfur that is in the protein coat, there was not inside the cell.3203

              It was only associated with the protein ghosts. That is what they will call the ghosts, it is the empty phage.3214

              This is really great, DNA is what is being passed on, not protein, this is huge.3221

              In the same year, we have Rosalyn Franklin.3232

              Rosalyn Franklin is an English chemist and one of the premier X-ray crystallographers of her time.3237

              This in fact is a picture of hers, called photo 51, this shows the diffraction pattern of DNA.3246

              If you can actually look at it, we can see that we have a double helical nature.3254

              We can even see the minor groove and the major groove, each one in DNA.3259

              This is an amazing picture, especially at the time.3267

              Unfortunately for Rosalyn Franklin, someone in her laboratory showed this picture, photo 51,3271

              to some competing scientist without her authorization.3283

              Those competing scientists are very well known now.3290

              The names of those competitors are James Watson and Francis Crick.3298

              A year later after getting that picture, that photo 51 from Rosalyn Franklin, they deduced the double helical structure of DNA.3303

              They published their article in the Nature journal, it was only one page long.3313

              It is one of the highest, or if not the highest, cited paper from that journal.3320

              What they said in their paper was that two DNA strands are held together by hydrogen bonds and 3329

              that is between the opposing strands.3338

              The bases coming together, make those hydrogen bonds.3342

              They said base pair, and they are specific, A pairs with T, G pairs with C only.3346

              We have already talked about this, but at the time that was a noble insight.3351

              They said that the sequence of one strand defines the sequence of the other strand,3358

              meaning that it is complementary.3361

              They also noted that it was anti parallel.3366

              Remember, 5 prime down to 3 prime for one strand, 5 prime up to 3 prime for the other strand.3368

              In that one of the last sentences, they stated that the specific base pairing suggests a possible copying mechanism.3376

              This was the whole basis of why DNA could not be the genetic material, as seen before,3387

              because it could not be copied.3395

              Now, they are saying that the phosphate backbone is on the outside, 3398

              the bases are on the inside, hydrogen bonded to each other, they are complementary.3401

              Therefore, we could probably see a situation where you can copy this pretty easily, although, 3405

              they did not propose the mechanism.3413

              As an example based on Watson and Crick’s solution, fill in this sequence on the bottom strand of DNA following what they said.3417

              Remember, A’s pair with T’s, G’s pair with T’s.3431

              DNA strands are anti parallel.3435

              Remember, we have the 5 prime to 3 prime on the top strand.3438

              We have the 5 prime to 3 prime down to the opposite on the bottom strand.3444

              If we want to make our bonds, T pairs with A, A pairs with T, C pairs with G, G pairs with C, C pairs with G.3450

              Let us not forget, how many bonds?3463

              A and T makes two hydrogen bonds, G and C make three hydrogen bonds.3467

              This would be our phosphate backbone, right here, of one strand, this is the phosphate backbone of another strand.3477

              A few years after Watson and Crick deduced the structure of DNA helix, 3491

              we had an American biochemist named Arthur Kornberg, he isolated this protein from a bacteria that he called DNA polymerase 1.3497

              He showed that DNTP or deoxyribonucleotide triphosphate, they say that DNTP’S meaning it could be an A, G, T, or C.3507

              He said that DNTP’s and a DNA molecule will require for DNA synthesis.3520

              He showed using templates with different base composition, whether it is high AT or high GC ratio, 3531

              he showed that the newly synthesized DNA molecules had a similar base composition.3538

              Confirming, Watson and Crick’s saying that there was the complimentary between the two strands.3543

              Kornberg established that the strand of DNA served as a template for DNA synthesis.3550

              But still, he could not way off a mechanism by which it happened.3557

              There were three mechanisms that we are offered at the time.3564

              Now, we had semi-conservative in which we have here, we started with our parent strand, all red.3569

              The two new daughter helices, one of the strand would be completely parental and one of the strand would be completely new.3579

              We have conservative, where it is just like a photocopy mechanisms of the two daughters strands.3589

              One would be completely old DNA, one would be completely new DNA.3594

              We have dispersive, in which case both of the daughter molecules would have new and old.3599

              But we would have stretches where both strands were completely old 3606

              and stretches where both strands are completely new DNA sequence.3611

              How do we discover what type of mechanism this is?3616

              Two years later, we have Meselson and Stahl showing that DNA replication is semi-conservative,3622

              meaning you have the original DNA.3629

              When it is newly made, we have one strand being completely old and one strand being completely new.3642

              How did they do this, which is a really ingenious experiment?3653

              DNA was made denser or heavy, by adding heavy isotope of nitrogen, some nitrogen 15.3658

              Then it was subjected to high speed centrifugation through this dense medium of chloride.3666

              You either grew DNA in what is called light nitrogen, the normal N14, or the heavy nitrogen the N15.3673

              You call that heavy or light DNA.3682

              They do grew through 14 generations, so that there was no bias coming in.3686

              They are all different.3692

              You are either completely in 15 or completely in 14, that was what it was showing.3694

              After one round of DNA replication, it opposes the light isotopes.3701

              All the daughter molecules have an intermediate density or heavy light, from 100% heavy to 100% intermediate.3710

              And then, what they did is they did one more replication.3724

              At the point, they saw a reduction of the medium, the intermediate, down to 50%.3729

              They saw 50% being fully light.3736

              This demonstrates that DNA replication is semi-conservative because you were having the old parental strand being the heavy.3742

              You grew it only in heavy to start with, then you started growing it in light.3751

              You can only be adding light, you could not add more heavy.3758

              By adding, by growing from completely heavy to intermediate, after one replication, 3763

              it has to be half and half, half old and half new.3771

              This does not necessarily mean that, right there that breaks away conservative.3778

              We can still have distributive or disperse, as well as semi-conservative.3785

              What they did is, they did more and more generations and found that as you increase the generations,3790

              you are not adding any more of that old stuff.3797

              You are not distributing in between strands; its every new strand is going to be a light strand.3800

              That is how they can figure that it was semi-conservative replication, that is a big deal here.3805

              That is the end of our DNA, the discovery of the genetic material and how it is replicated.3814

              This is a quick overview on the discovery of RNA, we will talk more about RNA later.3821

              Ribosomal RNA is one of the three types of RNA.3828

              rRNA was discovered in the 50’s by Albert Claude and George Palade.3832

              Ribosomal RNA is important for the structure of ribosomes, just a structural purpose.3841

              Transfer RNA is what is responsible for bringing in amino acids to the ribosome, 3849

              to match up with that particular anticodon in the mRNA.3858

              MRNA was found in 1956 by Zamecnik and Hoagland.3863

              Messenger RNA which is made from DNA and is responsible for dictating the sequence of amino acids3869

              for protein synthesis at the ribosome, was discovered in 1960 by Brenner, once again from Francis Crick.3878

              Now that we have learn about our DNA and RNA, 3886

              we should talk quickly about the central dogma in molecular biology, what is that really mean?3889

              This is something that we are going to talk about many times throughout this course.3900

              The simplest way to explain it is that DNA can make more DNA and that is called the process of replication.3905

              DNA can be turned into RNA, this is the metabolic process of transcription.3926

              Finally, RNA can be turned into protein via the process of translation.3942

              This is what everything that we believe in molecular biology follows.3954

              One thing that violates the central dogma is something that you might be familiar with, that is called reverse transcription.3961

              This is turning RNA back into DNA, we see this in the type of enzyme, such as retroviruses.3982

              They have a sort of enzyme called reverse transcriptase and that is able to turn RNA back into DNA.3991

              This is an important thing biologists always have in mind, when we are thinking about the molecular biology central dogma.4001

              RNA can be made into protein, how do we figure that out?4009

              How do we figure out which RNA will turn into which amino acids?4013

              Cracking the genetic code, this is important.4019

              If you remember, the genetic code, if we have not learned yet,4022

              the genetic code is what tells us what triplet will repeat found in an mRNA will give us a specific amino acid.4026

              In 1961, we have an American biochemist and geneticist named Marshall Nirenberg. 4036

              He discovered the first DNA triplet that would go on to make an amino acid.4041

              He did this by taking a bunch of nucleic acid, RNA, but only was made up of U’s.4046

              He fed this through the ribosome, in a cell extract, and only phenylalanine amino acids were made.4056

              He found out that the first triplet codon ever distinguished was UUU, that coded for phenylalanine.4065

              It took about 5 more years and some other researchers helped, but the code was completely finished in 1966.4075

              What they found is that they were 64 possibilities of triplet repeats or triplet codons.4082

              Each one of these could code for an amino acid.4096

              They thought, three of them they found, these are important, 4100

              were found to not actually add an amino acid and instead cause the release of the polypeptide chain from the ribosome.4106

              The other 61, other than these 3, the 61 possible codons all coded for amino acids.4114

              What is also very important is that, for example, let us look at this.4127

              4 of these different codons will code for serine amino acid.4132

              This is what we call the degeneracy of the genetic code, meaning that we can get the same amino acid from multiple different mRNA bases, 4139

              meaning also since we got the mRNA from the DNA, we can have different genetic sequences giving us the same amino acid sequences.4150

              I hope you enjoyed the lesson, thank you very much for coming and please come back to