1. The Molecular Basis of Inheritance
Chapter 16

2. Life’s Operating Instructions
Hereditary information is encoded in DNA (deoxyribonucleic acid)
Reproduced in all cells of the body
Transmitted to offspring by chromosomes in gametes
DNA directs the development of biochemical, anatomical, physiological, and behavioral traits

3. DNA= Deoxyribonucleic acid
Located in nucleus of cell
Genetic material inherited from parents
Genes code for specific proteins with unique code of nucleotides
Monomers= nucleotides
3 parts to nucleotide
5 carbon sugar (deoxyribose)
Phosphate group
Nitrogenous base

4. DNA Nucleotides form polynucleotides Double helix structure
2 polynucleotides wrap around each other
Nitrogenous bases pair in center between 2 backbones
Strands are complementary
4 nitrogenous bases
Adenine-Thymine
Cytosine-Guanine

5. DNA 3’ 5’ Strands are anti-parallel
Two ends of strand are different from each other
One end has a phosphate attached to a 5’ carbon
Other end has a hydroxyl group attached to a 3’ carbon

6. Chromosome Structure
Bacterial chromosome= double-stranded, circular DNA molecule associated with a small amount of protein
In bacteria, the DNA is “supercoiled” and found in a region of the cell called the nucleoid
Eukaryotic chromosomes have linear DNA molecules associated with a large amount of protein
Chromatin, a complex of DNA and protein, is found in the nucleus of eukaryotic cells

7. Chromosome Structure
In humans, each cell has DNA comprised of ~6 billion base pairs
Each diploid cell contains ~2 m of DNA
In total, humans contain ~100 trillion m of DNA
Enough to circle equator of Earth 2.5 million times!

8. Chromosome Structure
Most chromatin is loosely packed in the nucleus during interphase and condenses prior to mitosis
Loosely packed chromatin is 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
DNA fits into the nucleus through an elaborate, multilevel system of packing

9. Figure 16.22a
Nucleosome (10 nm in diameter)
DNA double helix (2 nm in diameter) H1
Histone tail
Figure Exploring: Chromatin Packing in a Eukaryotic Chromosome
Histones
Nucleosomes, or “beads on a string” (10-nm fiber)
DNA, the double helix
Histones
The DNA molecule binds with proteins known as histones, due to a negative charge on the strands of the DNA molecule and positive charges on histones

10. Figure 16.22a
Nucleosome (10 nm in diameter)
DNA double helix (2 nm in diameter) H1
Histone tail
Figure Exploring: Chromatin Packing in a Eukaryotic Chromosome
Histones
Nucleosomes, or “beads on a string” (10-nm fiber)
DNA, the double helix
Histones
Nucleosome is a histone complex with the DNA molecule wrapped around twice. The histone tails (amino end of protein) extend outward. The strands of DNA between the nucleosomes are called “linker DNA”.

11. Figure 16.22b
Chromatid (700 nm)
30-nm fiber
Loops
Scaffold
300-nm fiber
30-nm fiber
Figure Exploring: Chromatin Packing in a Eukaryotic Chromosome
Interactions between histone tails and linker DNA result in further compaction into 30-nm fiber
Replicated chromosome (1,400 nm)
Looped domains (300-nm fiber)
Metaphase chromosome

12. Figure 16.22b
Chromatid (700 nm)
30-nm fiber
Loops
Scaffold
300-nm fiber
30-nm fiber
Figure Exploring: Chromatin Packing in a Eukaryotic Chromosome
This fiber forms loops called looped domains attached to a protein scaffold, compacting material into 300 nm fiber
Replicated chromosome (1,400 nm)
Looped domains (300-nm fiber)
Metaphase chromosome

13. Figure 16.22b
Chromatid (700 nm)
30-nm fiber
Loops
Scaffold
300-nm fiber
30-nm fiber
Figure Exploring: Chromatin Packing in a Eukaryotic Chromosome
The looped domains condense further into the chromosomes visible during the stages of mitosis
Replicated chromosome (1,400 nm)
Looped domains (300-nm fiber)
Metaphase chromosome

14. Genetic Material
Early in the 20th century, the identification of the molecules of inheritance loomed as a major challenge to biologists
T. H. Morgan’s group showed genes are located on chromosomes
2 components of chromosomes—DNA and protein—became candidates for the genetic material

15. Genetic Material Frederick Griffith (1928)
Experiments with two strains of a bacteria causing pneumonia
one pathogenic and one harmless
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

16. Genetic Material
Studies in 1944 by Oswald Avery, Maclyn McCarty, and Colin MacLeod provided experimental evidence that only DNA worked in transforming harmless bacteria into pathogenic bacteria
In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next
Made DNA a more credible candidate for the genetic material

17. Genetic Material
At this time, it was known that DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group
Two findings became known as Chargaff’s rules
The base composition of DNA varies between species
In any species the number of A and T bases are equal and the number of G and C bases are equal

18. Genetic Material
More evidence for DNA as the genetic material came from studies of viruses that infect bacteria
Such viruses, called bacteriophages (or phages), are widely used in molecular genetics research
In 1952, Alfred Hershey and Martha Chase designed an experiment using a phage known as T2 and E. coli cells

19. Radioactivity (phage protein) in liquid Phage
Figure
EXPERIMENT
Empty protein shell
Radioactive protein
Radioactivity (phage protein) in liquid
Phage
Bacterial cell
Batch 1: Radioactive sulfur (35S)
DNA
Phage DNA
Centrifuge
Radioactive DNA
Pellet (bacterial cells and contents)
Figure 16.4 Inquiry: Is protein or DNA the genetic material of phage T2?
Batch 2: Radioactive phosphorus (32P)
Centrifuge
Radioactivity (phage DNA) in pellet
Pellet

20. Genetic Material Experiment with T2 and E. coli cells
Results showed only one of the two components of T2 (DNA or protein) enters an E. coli cell during infection
Concluded that the injected DNA of the phage provides the genetic information

21. DNA
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

22. DNA
Franklin’s picture was used by James Watson and Francis Crick to model the structure of DNA
DNA was helical
Width of the helix and spacing of nitrogenous bases
The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix

23. Sugar-phosphate backbone Strands are anti-parallel
Figure 16.7
Nitrogenous bases
5 end C G
Hydrogen bond C G
3 end G C G C T A
3.4 nm T A G C G C C G A T
1 nm C G T A C G G C C G A T
Figure 16.7 The double helix. A T
3 end A T
0.34 nm
5 end T A
(a)
Key features of DNA structure
(b) Partial chemical structure
Space-filling model
(c)
Sugar-phosphate backbone
Strands are anti-parallel

24. Base Pairing
Purine  purine: too wide
Pyrimidine  pyrimidine: too narrow
Purine  pyrimidine: width consistent with X-ray data
Figure 16.UN01 In-text figure, p. 310
Watson and Crick reasoned that the pairing was more specific
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

25. Sugar Sugar Adenine (A) Thymine (T) Sugar Sugar Guanine (G)
Figure 16.8 Base pairing in DNA.
Sugar
Sugar
Guanine (G)
Cytosine (C)

26. Form=Function
Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material
Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication
In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules

27. Watson and Crick’s semiconservative model of replication
After replication, each daughter molecule will have one old strand (from the parent molecule) and one newly made strand 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
(a) Parent molecule
(b)
Separation of strands
(c)
“Daughter” DNA molecules, each consisting of one parental strand and one new strand
Figure 16.9 A model for DNA replication: the basic concept.
Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new)
Rejected by later experiments by Matthew Meselson and Franklin Stahl

28. DNA Replication
Replication begins at origins of replication, where the two DNA strands are separated, opening up a replication “bubble”
Bacterial DNA has one origin of replication for its circular DNA
A eukaryotic chromosome may have hundreds or even thousands of origins of replication, increasing speed of replication
Replication proceeds in both directions from each origin, until the entire molecule is copied
At the end of each replication bubble is a replication fork, a Y-shaped region where new DNA strands are elongating

30. DNA Replication: Duplicating the code
At the replication forks, both strands replicated at same time in the 5’ to 3’ direction

31. DNA Replication: Duplicating the code
Helicase- unwinds double helix

32. DNA Replication: Duplicating the code
Topoisomerase- prevents overwinding at replication fork by breaking, swiveling, and rejoining DNA strands

33. DNA Replication: Duplicating the code
Single-strand binding proteins bind to and stabilize single-stranded DNA

34. DNA Replication: Duplicating the code
DNA primase- start an RNA chain from scratch and adds RNA nucleotides one at a time using the parental DNA as a template

35. DNA Replication: Duplicating the code
RNA primer- short (5–10 nucleotides long) RNA molecule that serves as the starting point for the new DNA strand

36. DNA Replication: Duplicating the code
DNA polymerases- catalyze the elongation of new DNA at a replication fork by adding nucleotides only to the free 3’ end of a growing strand

37. Nucleoside triphosphate
Figure 16.14
New strand
Template strand 5 3 5 3
Sugar A T A T
Base
Phosphate C G C G G C G C
DNA polymerase OH 3 A T A
Figure Incorporation of a nucleotide into a DNA strand. T P OH P
P i P P C 3
Pyrophosphate C OH
Nucleoside triphosphate
2 P i 5 5

38. DNA Replication: Duplicating the code
Leading strand: Template strand is 3’ to 5’
Lagging strand: Template strand is 5’ to 3’

39. DNA Replication: Duplicating the code
DNA polymerase synthesizes the leading strand continuously, moving toward the replication fork in 5’ to 3’ direction

40. DNA Replication: Duplicating the code
To elongate the lagging strand, DNA polymerase must work in the direction away from the replication fork

41. DNA Replication: Duplicating the code
Lagging Strand made by Okazaki fragments
-small sections of DNA made in 5’ to 3’ direction

42. DNA Replication: Duplicating the code
DNA ligase- joins the Okazaki
fragments

43. Preventing Mistakes
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
Mismatch repair= repair enzymes correct errors in base pairing
Nucleotide excision repair= a nuclease cuts out and replaces damaged stretches of DNA
Error rate after proofreading repair is low but not zero
Sequence changes may become permanent and can be passed on to the next generation
These mutations are the source of the genetic variation upon which natural selection operates

44. Replicating the Ends of DNA Molecules
Replication mechanism in eukaryotic cells provides no way to complete the 5 ends
Repeated rounds of replication produce shorter DNA molecules with uneven ends
Not a problem for prokaryotes with circular chromosomes
Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called telomeres
Repetitive DNA sequences
Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules
It has been proposed that the shortening of telomeres is connected to aging

45. Replicating the Ends of DNA Molecules
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, preventing this problem
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