1. Chapter 25: Molecular Basis of Inheritance
DNA was shown to be the genetic material (rather than proteins) by a simple experiment.
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2. Viral DNA is labeled
Fig 25.1
In the first experiment, phage (viral) DNA was labeled with radioactive 32P. The phage was allowed to attach to and inject its genetic material into E. coli cells. Then the culture was agitated to remove the remaining phage material outside the bacterial cells. In this experiment, investigators found most of the 32P-labeled DNA in the cells and not in the liquid medium.
Different parts of the phage were radioactively labeled (shown in red).

3. Viral capsid is labeled
Fig 25.1
In the second experiment, phage protein in capsids was labeled with 35S. The phages were allowed to inject their genetic material into E. coli bacterial cells. Scientists this time found the 35S-labeled protein in the liquid medium and not in the bacterial cells and concluded protein was not the genetic material.
The experiments showed that only the virus DNA entered the bacteria and produced new viruses.

4. One pair of bases
Fig 25.2
Pyrimidine
DNA is a polynucleotide composed of a phosphate, a sugar, and four nitrogen-containing bases: adenine (A), thymine (T), guanine (G), and cytosine (C).
Purine
Notice that the 3’ and 5’ refer to a numbering system for the carbon atoms that make up the sugar.

5. The structure of DNA was determined by James Watson and Francis Crick in the early 1950’s and they showed that DNA is a double helix in which A is paired with T and G is paired with C.
This is called complementary base pairing because a purine (2 rings) is always paired with a pyrimidine (1 ring).

6. DNA double helix
Fig 25.2
When the DNA double helix untwists, it resembles a ladder:
Sides = sugar+phosphate
Rungs = complementary paired bases.
The two DNA strands are anti-parallel – they run in opposite directions
Hydrogen Bond
On the left is the DNA double helix. When the helix is unwound, a ladder configuration shows that the uprights are composed of sugar and phosphate molecules and the rungs are complementary bases. Notice that the bases in DNA pair in such a way that the phosphate-sugar groups are oriented in different directions. This means that the strands of DNA end up running antiparallel to one another, with the 3’ end of one strand opposite the 5’ end of the other strand.

7. Replication of DNA
DNA replication occurs during chromosome duplication; an exact copy of the DNA is produced with the aid of DNA polymerase.
DNA polymerase is an enzyme.

8. Overview of DNA replication
Fig 25.3
Hydrogen bonds between bases break and enzymes “unzip” the molecule.
Each old strand of nucleotides serves as a template for each new strand.
Replication is called semiconservative because each new double helix is composed of an old (parental) strand and a new (daughter) strand.

9. Ladder configuration and DNA replication
New nucleotides move into complementary positions and are joined by DNA polymerase.
The process is semiconservative. Each new double helix is composed of an old strand and a newly-formed strand.
Fig 25.4
Old Strands
Use of the ladder configuration better illustrates how complementary nucleotides available in the cell pair with those of each old strand before they are joined together to form a daughter strand.
New Strands

10. Gene Expression
A gene is a segment of DNA that specifies the amino acid sequence of a protein.
Gene expression occurs when gene activity leads to a protein product in the cell.
A gene does not directly control protein synthesis; DNA is transcribed into RNA, RNA is translated in amino acids which are used to make proteins.

11. RNA (ribonucleic acid)
Three types of RNA:
messenger RNA (mRNA) carries genetic information to the ribosomes, RNA copy of DNA
ribosomal RNA (rRNA) is found in the ribosomes, and
transfer RNA (tRNA) transfers amino acids to the ribosomes, where the protein product is synthesized.

12. Structure of RNA
RNA is a single-stranded nucleic acid in which A pairs with U (uracil) while G pairs with C.
DNA=T-A;G-C RNA=U-A;G-C
Fig 25.5
Like DNA, RNA is a polymer of nucleotides. In an RNA nucleotide, the sugar ribose is attached to a phosphate molecule and to a base, either G, U, A, or C. Notice that in RNA, the base uracil replaces thymine as one of the pyrimidine bases. RNA is single-stranded, whereas DNA is double-stranded.

13. Two processes are involved in the synthesis of proteins in the cell:
Transcription makes an RNA molecule complementary to a portion of DNA (a section of DNA instruction is copied).
Translation occurs when the sequence of bases of mRNA directs the sequence of amino acids in a polypeptide (instructions are followed to build a protein).

14. The Genetic Code
DNA specifies the synthesis of proteins because it contains a triplet code: every three bases stand for one amino acid.
Each three-letter unit of an mRNA molecule is called a codon.
The code is nearly universal among living organisms.
The fact that the genetic code is about universal in living things suggests that the code dates back to the first organisms on earth and that all living things are related.

15. Codons TTAGCCACGATC AATCGGTGCTAG AATCGGTGCTAG Double Stranded DNA
Each group of three bases = one codon
Each codon is the ‘code’ for a specific amino acid.

16. Messenger RNA codons Fig 25.6 123 = amino acid AUA = isoleucine
CCG = proline
GAU = aspartate
GAC = aspartate
Notice that in this chart, each of the codons (white rectangles) is composed of three letters representing the first base, second base, and third base. For example, find the rectangle where C for the first base and A for the second base intersect. You will see that U, C, A, or G can be the third base. CAU and CAC are codons for histidine; CAA and CAG are codons for glutamine.

17. Central Concept
The central concept of genetics involves the DNA-to-protein sequence involving transcription and translation.
DNA has a sequence of bases that is transcribed (copied) into a sequence of bases in mRNA.
Every three bases is a codon that stands for a particular amino acid.

18. Overview of gene expression
Fig 25.7
Transcription occurs when DNA acts as a template for mRNA synthesis. Translation occurs when the sequence of the mRNA codons determines the sequence of amino acids in a protein.

19. Transcription and mRNA synthesis
Fig 25.8
During transcription in the nucleus, a segment of DNA unwinds and unzips, and the DNA serves as a template for mRNA formation.
RNA polymerase joins the RNA nucleotides so that the codons in mRNA are complementary to the triplet code in DNA.
During transcription, complementary RNA is made from a DNA template. A portion of DNA unwinds and unzips at the point of attachment of RNA polymerase. A strand of mRNA is produced when complementary bases join in the order dictated by the sequence of bases in DNA. Transcription occurs in the nucleus, and the mRNA passes out of the nucleus to enter the cytoplasm.

20. Translation
Translation is the second step by which gene expression leads to protein synthesis.
During translation, the sequence of codons in mRNA specifies the order of amino acids in a protein.
Translation requires several enzymes and two other types of RNA: transfer RNA and ribosomal RNA.

21. Transfer RNA
During translation, transfer RNA (tRNA) molecules attach to their own particular amino acid and travel to a ribosome.
Through complementary base pairing between anticodons of tRNA and codons of mRNA, the sequence of tRNAs and their amino acids form the sequence of the polypeptide.

22. Transfer RNA: amino acid carrier
Fig 25.10
Transfer RNA: amino acid carrier
A tRNA is a polynucleotide that folds into a bootlike shape because of complementary base pairing. At one end of the molecule is its specific anticodon – in this case UCG; at the other end an amino acid attaches that corresponds to this anticodon – in this case serine.

23. Anticodon UUA AAUCGGUGCUAG mRNA Anticodon for the first codon
Part of tRNA
UUA
AAUCGGUGCUAG
mRNA
Codons

24. Ribosomal RNA
Ribosomal RNA, also called structural RNA, is made in the nucleolus.
Proteins made in the cytoplasm move into the nucleus and join with ribosomal RNA to form the subunits of ribosomes.

25. Translation Requires Three Steps
During translation, the codons of an mRNA base-pair with tRNA anticodons.
Protein translation requires these steps:
Chain initiation
Chain elongation
Chain termination.
Enzymes are required for each step, and the first two steps require energy.

26. Chain Initiation
Fig 25.12
First, a small ribosomal subunit attaches to the mRNA near the start codon.
The anticodon of tRNA, called the initiator RNA, pairs with this codon.
Then the large ribosomal subunit joins.
During initiation, a small ribosomal subunit binds to mRNA; an initiator tRNA with the anticodon UAC pairs with the codon AUG.
The large ribosomal subunit completes the ribosome. Initiator tRNA occupies the first binding site. The second binding site is ready for the next tRNA.

27. Chain Elongation
Fig 25.12
The ribosome moves forward and the tRNA at the second binding site is now at the first site, a sequence called translocation.
The previous tRNA leaves the ribosome and picks up another amino acid before returning.
First, a tRNA-amino acid approaches the second binding site of the ribosome.
Second, two tRNAs can be at the ribosome at one time; the anticodons are paired to the codons.
Third, as the initiator tRNA leaves the first binding site, its amino acid is passed to the resident tRNA-amino acid complex.
Finally, the ribosome has moved forward, making room for the next incoming tRNA-amino acid complex.

28. Chain Termination
Fig 25.12
Chain termination occurs when a stop-codon sequence is reached.
The polypeptide is enzymatically cleaved from the last tRNA by a release factor.
A newly synthesized polypeptide may function alone or become part of a protein.
The ribosome comes to a stop codon on the mRNA.
Protein synthesis ceases as ribosomal subunits dissociate. The completed polypeptide, the last tRNA, and the mRNA molecule are released.

29. Polyribosome structure and function
Fig 25.11
At the top is a side view of a ribosome that shows the positioning of mRNA and the growing protein. In the middle is the frontal view of a ribosome. Finally, several ribosomes, collectively called a polyribosome, move along an mRNA at one time. Therefore, several proteins can be made at the same time.
Several ribosomes may attach and translate the same mRNA, therefore the name polyribosome.

30. Review of Gene Expression
DNA in the nucleus contains a triplet code (codons); each group of three bases stands for one amino acid.
During transcription, an mRNA copy of the DNA template is made.
The mRNA joins with a ribosome, where tRNA carries the amino acids into position during translation.

31. Gene expression
Fig 25.13
Gene expression leads to the formation of a product, most often a protein. The two steps required for gene expression are translation, which occurs in the nucleus, and translation, which occurs in the cytoplasm at the ribosomes.
One DNA strand serves as a template.
mRNA is processed before leaving the nucleus.
mRNA moves into the cytoplasm and becomes associated with ribosomes.
tRNAs with anticodons carry amino acids to the mRNA.
Anticodon-codon complementary base pairing occurs.
The peptide will be transferred to the tRNA-amino acid at the second binding site, and the tRNA at the first binding site will depart; the ribosome then moves forward.

32. Gene Mutations
A gene mutation is a change in the sequence of bases within a gene.

33. Frameshift Mutations
Frameshift mutations involve the addition or removal of a base during the formation of mRNA; these change the genetic message by shifting the “reading frame.”
Codon sequence:
THE CAT ATE THE RAT
If C in cat is removed:
THE ATA TET HER AT

34. Point Mutations
Point mutation (3 types) - The change of just one nucleotide causing a codon change
-can cause the wrong amino acid to be inserted in a polypeptide.
1) Silent mutation, change in the codon results in the same amino acid.
CUC and CUA both code for Leucine

35. 2) Nonsense mutation - If a codon is changed to a stop codon, the resulting protein may be too short
3) Missense mutation - the substitution of a different amino acid, the protein cannot reach its final shape
An example is Hbs which causes sickle-cell disease.

36. Sickle-cell disease in humans
Fig 25.17
Sickle-cell disease in humans
Chain is 146 AA’s long
One change in the sixth position
Portion of the chain in normal hemoglobin HbA and in sickle-cell hemoglobin HbS. Although the chain is 146 amino acids long, the one change from glutamate to valine in the sixth position results in sickle-cell disease. Glutamate has a polar R group, while valine has a nonpolar R group, and this causes HbS to be less soluble and to precipitate out of solution, distorting the red blood cell into the sickle shape.
GUA & GUG = Valine
GAA & GAG = glutamate

37. Cause and Repair of Mutations
Mutations can be spontaneous or caused by environmental influences called mutagens.
Mutagens include radiation (X-rays, UV radiation), and organic chemicals (in cigarette smoke and pesticides).
DNA polymerase proofreads the new strand reducing mistakes to one in a billion nucleotide pairs replicated.

38. Cancer: A Failure of Genetic Control
Cancer is a genetic disorder resulting in a tumor, an abnormal mass of cells.
‘Unregulated Cell Growth’
Carcinogenesis - the development of cancer.
Cancer cells fail to undergo apoptosis, or programmed cell death.
Cancer may actually take years to develop.
Malignancy is present when metastasis establishes new tumors distant from the primary tumor. Cancer cells produce proteinase enzymes that degrade the basement membrane and allow cancer cells to invade underlying tissues.

39. Cancer cells
Cancer cells lack differentiation, form tumors, undergo angiogenesis and metastasize.
Cancer cells differ from normal cells in many ways. Cancer cells exhibit uncontrolled growth, have no contact inhibition, are disorganized and multilayered, nondifferentiated with abnormal nuclei, and do not undergo apoptosis.

40. Angiogenesis (stimulated by cancer cells) is the formation of new blood vessels.
Metastasis is invasion of other tissues by establishment of tumors at new sites.
A patient’s prognosis is dependent on the degree to which the cancer has progressed.
Prognosis is the probable outcome. Prognosis is dependent on (1) whether the tumor has invaded surrounding tissues, (2) if there is any lymph node involvement, and (3) whether there are metastatic tumors in distant parts of the body.

41. Origin of Cancer
1) Mutations in genes for DNA repair enzymes can contribute to cancer.
2) Mutations in genes that code for proteins regulating structure of chromatin can promote cancer.

42. 3) Mutations in Proto-oncogenes or tumor-suppressor genes can prevent normal regulation of the cell cycle.
4) Telomeres are DNA segments at the ends of chromosomes that normally get shorter and signal an end to cell division; cancer cells have an enzyme that keeps telomeres long.

43. Oncogenes Proto-oncogenes – involved with stimulating cell division
Proto-oncogenes can undergo mutations to become cancer-causing oncogenes.
Oncogenes are responsible for uncontrolled cell growth.

44. Tumor-Suppressor Genes
Tumor-suppressor genes – involved with suppressing cell division.
When Tumor-suppressor genes mutate, they stop suppressing the cell cycle and it can occur nonstop.
The balance between stimulatory signals and inhibitory signals determines whether proto-oncogenes or tumor-suppressor genes are active.

45. Causes of cancer
Two types of regulatory pathways extend from the plasma membrane to the nucleus. In the stimulatory pathway, plasma membrane receptors receive growth-stimulatory factors. Then proteins within the cytoplasm and proto-oncogenes within the nucleus stimulate the cell cycle. In the inhibitory pathway, plasma membrane receptors receive growth-inhibitory factors. Then proteins within the cytoplasm and tumor-suppressor genes within the nucleus inhibit the cell cycle from occurring. Whether cell division occurs or not depends on the balance of stimulatory and inhibitory signals received. Hereditary and environmental factors cause mutations of proto-oncogenes and tumor-suppressor genes. These mutations can cause uncontrolled growth and a tumor.
Agents that can bring about the activation of oncogenes and the inactivation of tumor-suppressor genes include heredity, organic chemicals, radiation, and viruses.

46. Stop

47. Chapter 23:
Know why Gregor Mendel is important
What does homologous, allele, loci, gene, chromosome, genotype, and phenotype mean?
What is the relationship between dominant and recessive alleles. How does inheritance work? How many copies of each allele are found in gametes?
What is a one-trait cross? What are the possible outcomes (genotype & phenotype) based on the parents genotypes/phenotypes. Same questions for two-trait cross.
What is a pedigree chart and what is it used for. Understand how to do a pedigree analysis.
What is an autosome? What is autosomal dominant versus autosomal recessive? Also polygenic traits, incomplete dominance,and codominance.\
Review blood type and sickle cell disease.

48. Do the practice problems!!
Chapter 24:
Know what karyotyping is and what it can be used for.
Understand how changes in chromosome number, what can happen, and why that is important.
Understand how changes in sex-chromosomes affect a persons phenotype/genotype and associated syndromes.
How can changes in chromosome structure occur?
What is a sex-linked trait and how are they inherited?**
Understand how autosomal and sex-linked inheritance of traits works.
Do the practice problems!!

49. Chapter 25:
How was it discovered that DNA was the source of genetic information
What is the structure of DNA? How is it replicated?
What is RNA? How is it different than DNA? What types of RNA are there and why?
What is a codon? What are they used for?
What is gene expression? What are the processes that lead to gene expression.
Understand Translation and Transcription and all steps involved.
What are some types of gene mutations and how do they work.
Understand the mechanisms of cancer growth.