The Molecular Basis of InheritanceDeoxyribonucleic acid (DNA) -- is the genetic material that is transmitted from parents to offspringHistorical Background:1. 1940s -- Scientist knew that chromosomes carry hereditary material made of DNA and protein. Most researchers thought protein was the genetic material because:● Proteins are macromolecules with specificity● Not much was known about nucleic acids like DNA● DNA seemed too simple and uniform to account for the great variety of genetic traits2. Evidence that DNA can Transform Bacteria● 1928 -- Frederick Griffith’s experiments provided evidence that genetic material is a specific molecule, probably NOT protein.● Experiment ■ Pneumococcus bacteria come in two forms: smooth bacteria have capsules causing it be deadly (S); rough bacteria do not have capsules, not deadly (R). The smooth and rough phenotypes are inherited.a. A mice die, smooth strain is deadly.b. Mice ok, rough strain lacking capsule not pathogenicc. Heat killed S cells is not deadly here. The capsule does not cause illness because it still present in the heat-killed bacteria.d. Mixture of heat-killed S cells and Living R cells killed the mice AND living S cells were recovered from the blood of the dead miceConclusion:Rough cells had acquired, from the smooth cells, the ability to make the capsules and these bacteria produced new bacteria with the same deadly capsule trait. Griffith concluded the capsules were in an inherited trait. He called this process of DNA transfer and the subsequent transfer of traits from one organism to another Transformation. ● Transformation: the assimilation of external genetic material by a cell. (a cell absorbing DNA from another source)● Griffith could not answer the question of what the chemical nature of this “transforming” agent was.● His experiment did point to the fact that protein is not the genetic material. Heat denatures the protein capsule, but heat did not destroy the genetic material (DNA) in the heat-killed S cells. The protein capsule makes the bacteria deadly, but it is DNA that codes for the production of the capsule. The pathogenic DNA was taken up by the non-pathogenic R cells, giving them the new trait of being deadly.Most scientist still believed that protein and DNA was not a better choice as genetic material.1952 -- The Hershey-Chase Experiment: Provided evidence that DNA is the genetic material in viruses● Viruses are composed of DNA inside a protein coat. When a virus infects a cell, the virus DNA is injected into the cell. The protein capsules remains outside of the cell● Hershey and Chase infected bacterial cells with a virus. They added different radioactive tags to the protein and to the DNA of the virus and then traced where the radioactive protein and DNA ended up after cells were infected.Conclusion● Viral proteins remained outside the host cell.● Viral DNA was injected into the host cell.● The infected cells released new viruses with the tagged DNA material● This data provided evidence that nucleic acid (DNA) and not proteins are the hereditary material. Evidence that DNA was the genetic material in eukaryotic cells● A plant/ animal cell doubles its DNA before dividing● The doubled DNA is equally divided to the new cells● Body cells have twice the DNA of egg or sperm cells● DNA is species specific: scientist have found that the amount of DNA in different species of living things.1947 -- Chargaff studied the chemical makeup of DNA in a solution. In every species he studied, he found that:● The amount of Adenine bases = The amount of Thymine. → A=T● The amount of Guanine bases = The amount of Cytosine. → G=CBest known as the Chargaff’s Rules. His work aided the later work of Watson and Crick when they deduced the structure of the DNA molecule.Discovery of the Double Helix Structure of DNA1950s -- Finally, DNA was accepted as the genetic material, but it’s structure was still a mysteryScientist working on DNA: James Watson and Francis Crick; Maurice Wilkins and Rosalind Franklin● Without Franklin’s knowledge or permission, Wilkins showed Watson one of her x-ray photographs of DNA. When Watson saw the picture, it gave him the clue that DNA was a double-helix molecule with very specific measurements and structure.● A DNA molecule is composed of deoxyribose sugars and phosphate groups on the outside with nitrogenous bases inside. Watson and Crick were building a molecule model with the sugar-phosphate chains inside. Once they saw the photograph, they realized that the S-P chains were on the outside, bases inside, and the base pair width matched the size of the bases pairs Adenine -- Thymine; Guanine -- Cytosine● Chargaff’s Rule confirmed this.● Nucleotide → sugars + phosphate + base● Bases are bonded by weak hydrogen bonds.DNA ReplicationWatson and Crick’s model answered all the critics’ questions about how DNA can be the genetic material. The double helix shape allows the molecule to unzip in between the bases. Each old DNA strand can copy itself to create two new molecules exactly like the old one.Replication is very accurate due to proofreading enzymes that can fix mistakes in the bases.In human cells, there is only one mistake per one billion nucleotides!Because each new DNA molecule is composed of one ”old” and one “new” strand, the process is called semi-conservative.A Closer Look at ReplicationThe two DNA strands are antiparallel due to the bonding sites on the sugar molecules. The strands are labeled “5 to 3” or “3 to 5” corresponding to the number 3 and the number 5 carbons of the deoxyribose sugar ring● Helicases unwind the parents’ strands of DNA● DNA polymerase adds the new bases to the old bases● DNA ligase joins the Okazaki
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