Chapter 16 The Molecular Basis Of Inheritance PDF

Chapter 16 The Molecular Basis Of Inheritance The Search for the Genetic Material: Scientific Inquiry T. H. Morgan’s group showed that genes are located on chromosomes, two components of chromosomes (DNA and protein) became candidates for the genetic material ©...

Chapter 16 The Molecular Basis Of Inheritance The Search for the Genetic Material: Scientific Inquiry T. H. Morgan’s group showed that genes are located on chromosomes, two components of chromosomes (DNA and protein) became candidates for the genetic material © 2017 Pearson Education, Inc. Evidence That DNA Can Transform Bacteria Dr. Frederick Griffith in 1928 When he mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic Transformation- a change in genotype and phenotype due to assimilation of foreign DNA © 2017 Pearson Education, Inc. Evidence That Viral DNA Can Program Cells In 1952, Alfred Hershey and Martha Chase showed that DNA (not protein) is the genetic material They designed an experiment using bacteriophages and bacteria ‒ bacteriophages (or phages), viruses that infect bacteria They contain a protein coat and DNA inside They let a phage infect a bacteria and tracked where the protein and the DNA went. When the label the protein, the label did not enter the cell. So protein did NOT enter or infect the bacteria. When they labeled the protein, the label did go into the cell. So DNA DID enter/infect the bacteria. Evidence That Viral DNA Can Program Cells In 1952, Alfred Hershey and Martha Chase showed that DNA (not protein) is the genetic material They designed an experiment using bacteriophages and bacteria ‒ bacteriophages (or phages), viruses that infect bacteria They concluded that the injected DNA of the phage provides the genetic information Chargaff’s Rules In 1950, Erwin Chargaff Two findings became known as Chargaff’s rules 1. The base composition of DNA varies between species 2. In any species the number of A and T bases is equal (A = T) and the number of G and C bases is equal (C = G) If Adenine makes up 36% of the DNA what percentage Is Guanine? If Cytosine makes up 27% of the DNA what percentage is thymine?  Building a Structural Model of DNA: Scientific Inquiry After DNA was accepted as the genetic material, the challenge was to determine how its structure accounts for its role in heredity Maurice Wilkins and Rosalind Franklin were using a technique called X-ray crystallography to study molecular structure Franklin produced a picture of the DNA molecule using this technique Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior © 2017 Pearson Education, Inc.  Why is it called the 5’ end? Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions) 5’ – phosphate 3’ – hydroxyl backbone phosphate ribose nitrogenous base Why is it called the 3’ end? Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions) 5’ – phosphate 3’ – hydroxyl Adenine & guanine are purines Thymine & cytosine are pyrimidines Notice A & T have 2 hydrogen bonds G & C have 3 hydrogen bonds  At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width Instead, pairing a purine (A or G) with a pyrimidine (C or T) resulted in a uniform width consistent with the X-ray data Purine + purine: too wide Pyrimidine + pyrimidine: too narrow Purine + pyrimidine: width consistent with X-ray data © 2017 Pearson Education, Inc.  Combine this with Chargaff’s Rule… In any species the number of A and T bases is equal (A = T) and the number of G and C bases is equal (C = G) … suggests that A (purine) pairs with T (pyrimidine) and G (purine) pairs with C (pyrimidine) Purine + purine: too wide Pyrimidine + pyrimidine: too narrow Purine + pyrimidine: width consistent with X-ray data © 2017 Pearson Education, Inc.  Watson and Crick reasoned that the pairing was more specific, dictated by the base structures They determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C) The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material If one strand is: ATGCCTAG…. The strand it’s paired with must be: ___________ DNA Replication and Repair Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication If one strand is: ATGCCTAG…. The complementary strand is: TACGGATG…. In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules © 2017 Pearson Education, Inc.  5′ 3′ A T C G T A A T G C 3′ 5′ (a) Parental molecule © 2017 Pearson Education, Inc.  5′ 3′ 5′ 3′ A T A T C G C G T A T A A T A T G C G C 3′ 5′ 3′ 5′ (a) Parental (b) Separation of molecule parental strands into templates © 2017 Pearson Education, Inc.  Original New strand strand 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ A T A T A T A T C G C G C G C G T A T A T A T A A T A T A T A T G C G C G C G C 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ (a) Parental (b) Separation of (c) Formation of new molecule parental strands strands complementary into templates to template strands 2 identical copies to the parent molecule! © 2017 Pearson Education, Inc.  Watson and Crick’s semiconservative model of replication predicts that when a double helix replicates, each daughter molecule will have one old strand (“conserved” from the parent molecule) and one newly made strand Competing models were: ‒ the conservative model (the two parent strands rejoin) ‒ the dispersive model (each strand is a mix of old and new) Meselson and Stahl experiment to confirm semiconservative model weighs more Any new DNA will weigh less © 2017 Pearson Education, Inc. Questions?  Getting Started :DNA replication Replication begins at particular sites called origins of replication, where the two DNA strands are separated, opening up a replication “bubble” A eukaryotic chromosome may have hundreds or even thousands of origins of replication Replication proceeds in both directions from each origin, until the entire molecule is copied © 2017 Pearson Education, Inc.  At the end of each replication bubble is a replication fork, a Y-shaped region where new DNA strands are elongating Helicases are enzymes that unzips the double helix at the replication forks Single-strand binding proteins bind to and stabilize single-stranded DNA they prevent the DNA from just coming back together Topoisomerase relieves the strain of twisting of the double helix by breaking, swiveling, and rejoining DNA strands (located upstream and untwists the DNA before Helicase unzips it, preventing tangling of DNA.) Topoisomerase Primase 3′ RNA 5′ 3′ primer 5′ Replication 3′ fork Helicase Single-strand binding proteins 5′ © 2017 Pearson Education, Inc.  Synthesizing a New DNA Strand DNA polymerases add nucleotides to a DNA strand require a primer to which they can add nucleotides The initial nucleotide strand is a short RNA primer that is synthesized by the enzyme primase A primer is short Primase can start an RNA chain from scratch and (5–10 nucleotides long), adds RNA nucleotides one at a time using the and the 3′ end serves as parental DNA as a template the starting point for the new DNA strand © 2017 Pearson Education, Inc.  DNA polymerase III adds DNA nucleotides to the primer. Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate As each monomer joins the DNA strand, via a dehydration reaction, it loses two phosphate groups as a molecule of pyrophosphate DNA Polymerase I eventually replaces RNA primers with DNA Can ONLY build DNA in the 5’  3’ direction on the new strand © 2017 Pearson Education, Inc.  Antiparallel Elongation DNA polymerases add nucleotides only to the free 3′ end of a growing strand; therefore, a new DNA strand can elongate only in the 5′ to 3′ direction Along one template strand of DNA, the DNA polymerase synthesizes a leading strand continuously, moving toward the replication fork To elongate the other new strand, called the lagging strand, DNA polymerase must work in the direction away from the replication fork The lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase Remember DNA is antiparallel 5′ 3′ A T C G T A A T G C © 2017 Pearson Education, Inc. 3′ 5′  3′ 1 Primase makes Primer for RNA primer. Origin of leading replication strand 5′ 3′ Template 5′ 3′ strand 5′ © 2017 Pearson Education, Inc.  3′ 1 Primase makes Primer for RNA primer. Origin of leading replication strand 5′ 3′ Template 5′ 3′ strand 5′ 2 DNA pol III 3′ RNA primer makes Okazaki for fragment 1 fragment 1. 5′ 3′ 1 5′ 3′ 5′ © 2017 Pearson Education, Inc.  3′ 1 Primase makes Primer for RNA primer. Origin of leading replication strand 5′ 3′ Template 5′ 3′ strand 5′ 2 DNA pol III 3′ RNA primer makes Okazaki for fragment 1 fragment 1. 5′ 3′ 1 5′ 3′ 5′ 3 DNA pol III detaches. 3′ Okazaki fragment 1 5′ 1 3′ 5′ © 2017 Pearson Education, Inc.  RNA primer for fragment 2 5′ Okazaki 4 Fragment 2 3′ fragment 2 is primed. 2 1 3′ 5′ © 2017 Pearson Education, Inc.  RNA primer for fragment 2 5′ Okazaki 4 Fragment 2 3′ fragment 2 is primed. 2 1 3′ 5′ 5′ 3′ 5 DNA pol I replaces RNA with DNA. 2 1 3′ 5′ © 2017 Pearson Education, Inc.  RNA primer for fragment 2 5′ Okazaki 4 Fragment 2 3′ fragment 2 is primed. 2 1 3′ 5′ 5′ 3′ 5 DNA pol I replaces RNA with DNA. 2 1 3′ 5′ 6 DNA ligase forms bonds between 5′ DNA fragments. 7 The lagging 3′ strand is complete. 2 1 3′ 5′ Overall direction of replication © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. What do each of these proteins do? Helicases Primase Topoisomerase DNA polymerase III DNA Polymerase I DNA ligase Single strand binding proteins  The DNA Replication Complex The proteins that participate in DNA replication form a large stationary complex, a “DNA replication machine” The DNA moves through the complex during replication Primase can act as a molecular break. © 2017 Pearson Education, Inc.  Proofreading and Repairing DNA Thymine dimer is a common error caused by UV damage DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides In mismatch repair of DNA, repair enzymes correct errors in base pairing DNA can be damaged by exposure to harmful chemical or physical agents such as cigarette smoke and X-rays; it can also undergo spontaneous changes In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DNA © 2017 Pearson Education, Inc. Evolutionary Significance of Altered DNA Nucleotides The error rate after proofreading and repair is low but not zero Sequence changes may become permanent and can be passed on to the next generation (ie. If it happens in gametes/ during meiosis) These changes (mutations) are the source of the genetic variation upon which natural selection operates and are ultimately responsible for the appearance of new species © 2017 Pearson Education, Inc. Replicating the Ends of DNA Molecules Limitations of DNA polymerase provides no way to complete the 5′ ends, so repeated rounds of Primer removed replication produce but cannot be shorter DNA replaced with DNA molecules with because there is no uneven ends 3’ end available for DNA polymerase. This is not a problem for prokaryotes, most of which have circular chromosomes © 2017 Pearson Education, Inc.  Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called telomeres Telomeres do not prevent the shortening of DNA molecules they do postpone the erosion of genes near the ends of DNA molecules Associated proteins prevent cell death pathways It has been proposed that the shortening of telomeres is connected to aging If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist © 2017 Pearson Education, Inc.  A chromosome consists of a DNA molecule packed together with proteins The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein In a bacterium, the DNA is “supercoiled” and found in a region of the cell called the nucleoid Loose DNA can Condensed DNA be expressed aren’t expressed © 2017 Pearson Education, Inc.  In the eukaryotic cell, DNA is precisely combined with proteins in a complex called chromatin Proteins called histones are responsible for the first level of packing in chromatin Unfolded chromatin resembles beads on a string, with each “bead” being a nucleosome, the basic unit of DNA packaging Chromatid (700 nm) Nucleosome DNA (10 nm in diameter) 30-nm double helix fiber (2 nm in diameter) Looped Scaffold domain H1 300-nm Histone tail Histones fiber Replicated chromosome (1,400 nm) © 2017 Pearson Education, Inc.  Interphase chromosomes occupy specific restricted regions in the nucleus, and the fibers of different chromosomes do not become entangled Hetero- Loosely packed chromatin is chromatin called euchromatin During interphase a few regions of chromatin (centromeres and telomeres) are highly condensed into heterochromatin Dense packing of the heterochromatin makes it difficult for the cell to express genetic information coded in these regions euchromatin © 2017 Pearson Education, Inc. Loosely packed chromatin in nucleus, during interphase  Function © 2017 Pearson Education, Inc.