Genetics Quiz: Genes and Translation

Course Information

• Course title: Molecular Genetics
• Course code: ABCS 355
• Credit hours: 2 credits
• Instructor: Bethel Kwansa-Bentum, PhD
• Institution: University of Ghana

Course Outline

• Structure and function of DNA and RNA
• Regulation of gene transcription and expression of prokaryotes
• Mutations and concomitant altered proteins
• Behavioral genetics, prokaryotic gene expression, gene mapping, and biomedical genetics

Objectives

• Discuss the path to the Watson and Crick model of DNA
• Discuss the Watson and Crick model of DNA
• Explain the processes of the Central Dogma
• Discuss the properties of the Genetic code
• Discuss how cells regulate expression of genes
• Differentiate between Mutations and Polymorphisms
• Explain the roles of genes in biomedicine and organism behavior
• Outline the importance of gene mapping

References

• Griffiths et al. (2010). Introduction to genetic analysis, 10th edition. W. H. Freeman and Company, New York.
• Gurbachan (2015). Essentials of Molecular Genetics. Alpha Science International Ltd., Oxford, U.K.
• Klug and Cummings (2003). Concepts of genetics. Upper Saddle River, Prentice Hall, New Jersey.
• Russell (2000). Fundamentals of Genetics, 2nd edition. Addison Wesley Longman.
• Snustad, Simmons, and Jenkins (1997). Principles of Genetics. John Wiley and Sons Inc. New York.
• Strachan and Read (2010). Human Molecular Genetics. 4th Edition. Garland Science, U.S.A.

Course Delivery Schedule (2021)

• Week 1 (April 6th): Path to the Watson and Crick model (contributions of scientists to understanding DNA)
• Week 2 (April 13th): Watson and Crick model of DNA, RNA structure (distinguishing nucleoside/nucleotide, DNA vs. RNA, significance of base-pairing)
• Week 3 (April 20th): The Central dogma (DNA replication, transcription, translation)
• Week 4 (April 27th): The Genetic Code (properties of the genetic code, types of mutations, types of polymorphisms)
• Week 5 (May 4th): Behavioral genetics, prokaryotic gene expression (significance of gene regulation, operon)
• Week 6 (May 11th): Gene mapping, biomedical genetics

The Path to Watson and Crick Model

• Early scientists' contributions to understanding DNA

Section Objectives (Page 7)

• Gene definition at the molecular level
• Scientists' contributions to understanding DNA's nature

Gene – The Unit of Heredity

• Genes are organized within chromosomes
• Locus is the physical location of a gene
• Alleles are different versions of a gene (e.g., blue/brown eye color allele)
• Genes determine almost all traits in an organism
• Genes consist of DNA

Characteristics of Genetic Material

• Information repository for the cell
• Transfer of information on demand
• Faithful replication to pass information across generations
• Stability to withstand mutations

Griffith's Transformation Experiment (1928)

• First experiment on gene transfer
• Used S-strain (lethal) and R-strain (non-lethal) bacteria.
• Heat-killed S-strain alone did not cause infection.

Avery, MacLeod, McCarty (1944)

• DNA, not proteins, can transform genetic properties.
• Used radioactive phosphorus to label DNA.

Hershey and Chase (1952)

• Definitive proof that DNA is the genetic material.

Rosalind Franklin (1952)

• X-ray diffraction images provided crucial insights into DNA structure, leading to the understanding of DNA's helical nature.

Summary (Page 14)

• Miescher's DNA identification
• Griffith's gene transfer experiment
• Avery, MacLeod, McCarty's demonstration of DNA's role in transformation.
• Hershey-Chase confirmation that DNA is genetic material.
• Franklin's x-ray diffraction images
• Watson & Crick's DNA structure model

Watson and Crick Model of DNA Structure (Page 15)

Objectives (Page 16)

• Distinguishing nucleoside/nucleotide
• Importance of nucleotide components
• Describing nucleotide linkages within chains
• Detailing base pairing importance
• Differentiating DNA/RNA structures
• Analyzing factors causing differences between species, individuals and cells.

Nucleotide

• Consists of a nitrogenous base, deoxyribose sugar, and a phosphate group.

The 5 Nitrogenous Bases

• Purines (guanine, adenine): two rings
• Pyrimidines (cytosine, thymine, uracil): one ring

The 4 Nitrogenous Bases in DNA (Page 19)

• DNA structure's backbone is of repeating sugar and phosphate residues connected by phosphodiester bonds.
• Bases attract each other via hydrogen-bonds.
• Phosphate groups are negatively charged, which enhances solubility in water.

The Double Helix (Page 20)

• DNA structure is a double helix made of two anti-parallel strands
• Nucleotide pairs are joined together by hydrogen bonds to form the "rungs" of the DNA "ladder".
• The two strands are antiparallel

The Two Strands are Complementary (Page 21)

• Adenine bonds with Thymine (2 Hydrogen bonds)
• Guanine bonds with Cytosine (3 Hydrogen bonds)
• Base pairing allows DNA to replicate itself

The Two Strands are Antiparallel (Page 22)

• The strands run in opposite directions (5' to 3' and 3' to 5')

Structure of DNA (Page 23)

• DNA is composed of two polynucleotide chains forming a double helix.
• Carries genetic instructions for the growth, development, functioning, and reproduction of known organisms.
• Each turn of the helix contains about 10.4 nucleotide pairs.

Erwin Chargaff's Rule (1950) (Pages 24-25)

• Number of purines equals the number of pyrimidines
• Adenine to thymine ratio and guanine to cytosine ratio are close to 1:1
• AT/GC ratio varies between species.

Differences Between Species (Pages 35-36)

• DNA percentages do not specify species differences.
• Vastly differing genome sizes can have similar nucleotide percentages
• Differences in species originate from variations in base sequence and total DNA present.

Differences Between Individuals of the Same Species (Page 38)

• Total DNA amount is roughly similar for individuals of the same species
• Variations in base sequence

Differences Between Cells of the Same Individual (Page 39)

• Differences in how genes are expressed
• Different genes and active gene sets found in various cell types

Differences Between Normal and Cancerous Cells (Page 40)

• Chromosome alterations are common in cancerous cells
• Cancer cells are often aneuploid (altered chromosome number)

Central Dogma of Biology (Page 41)

• Explains the flow of genetic information from DNA to RNA to protein
• Process of DNA replication, DNA transcription to RNA and RNA translation to protein.
• All 3 stages (replication, transcription, and translation) contain initiation, elongation, and termination steps each.

Replication (Pages 44-53)

• DNA replication is semi-conservative.
• Double-stranded DNA molecule gets copied to form two identical DNA molecules.
• Initiation steps: establishing replication origins, unwinding the DNA helix via helicase, stabilizing the single-stranded areas via single-strand binding proteins, and preventing supercoiling via DNA gyrase (in prokaryotes) or type II Topoisomerase (in eukaryotes)
• Initiation steps: RNA primer synthesis via primase for DNA polymerase which then extends the template DNA.
• Elongation steps: continuous synthesis on the leading strand, discontinuous synthesis to create Okazaki fragments on the lagging strand.
• Termination steps: process of expanding new DNA strands, ends of replication. Stabilization of newly synthesized DNA strands, removal of RNA primers via RNase H and connection of fragments via ligase.

Transcription (Pages 54-60)

• Information in DNA is copied into a messenger RNA (mRNA).
• Gene is the sequence of DNA transcribed into RNA.
• DNA safely stores genetic material as a reference or template.
• mRNA is complementary to DNA template sequence but has Uracil replacing Thymine.
• Initiation steps: locating target gene, binding RNA polymerase to promoter site.
• Elongation steps: RNA polymerase reads template DNA strand and extends the growing mRNA strand.
• Termination steps: RNA polymerase reaches terminator sequence in DNA, detaching from DNA and releasing mRNA.

Eukaryotic RNA Modifications (Page 61-62)

• Pre-mRNA modification: addition of 5' cap and poly-A tail to 3' end.
• Splicing of pre-mRNA: removal of introns, connecting exons to form mature mRNA.

Translation (Pages 63-72)

• mRNA is decoded to build polypeptide/protein chains.
• Codons of mRNA are read from 5' to 3' by tRNA molecules.
• tRNA has an anticodon that matches the mRNA codon and carries the specific amino acid.
• Ribosomes are protein-RNA complexes where tRNA binds to mRNA and amino acids are linked to form polypeptide chains.
• Initiation steps: small ribosomal subunit attaches to mRNA, initiator tRNA carrying methionine binds to start codon.
• Elongation steps: matching tRNA binds to next codon in A site, peptide bond is formed, tRNA in P site moves to E site, new tRNA enters A site. Process continues until stop codon.
• Termination steps: stop codon reaches A site, release factor binds to stop codon, separating polypeptide and ribosome.

Processing (Page 74)

• Following translation, polypeptide chains may be chemically altered, folded into 3D structures.
• Some proteins require chaperones for folding, special amino acid sequences direct them to specific locations.

Summary of Transcription and Translation (Page 75)

• Transcription takes place in the nucleus, copying DNA's instructions into mRNA.
• Translation happens within ribosomes, interpreting the mRNA code to assemble protein molecules.
• tRNA and ribosomes (rRNA) are used to convert mRNA sequence into amino acid sequence.

The Genetic Code (Pages 76-87)

• Defines how genetic code letters in RNA (U, C, A, G) create codons for 20 amino acids.
• Each codon is a combination of three letters; 64 possible codons
• AUG codon is the start codon, specifying methionine, and initiating peptide synthesis.
• UAA, UAG, and UGA are the stop codons
• Genetic code properties: Universal, unambiguous, redundant, triplet, non-overlapping, comma-less, co-linear.
• One gene produces one polypeptide

Properties of the Genetic Code (Pages 82-87)

• The universal genetic code is consistent in all living organisms
• Each codon uniquely codes for a specific amino acid
• Most amino acids are coded for by multiple codons (redundant).
• Codons are triplets (three letters).
• Codons are non-overlapping.
• The genetic code is comma-less (no punctuation between codons), co-linear (gene sequence corresponds to the polypeptide sequence) and shows gene-polypeptide parity.

Mutations and Polymorphisms (Pages 89-105)

• Mutation: any change in DNA sequence from normal.
• Types of mutations:
• Point mutations (change in a single nucleotide): silent, nonsence, missense (conservative/non-conservative)
• Insertion (addition of nucleotides): can cause frameshift mutations
• Deletion (removal of nucleotides): frameshift mutations
• Inversion (reversal of DNA segment): can change protein function
• Translocation (transfer of genes): genes from one chromosome to another
• Duplication: multiple copies of chromosomal regions, increasing protein levels

Causes of Mutations (Pages 101-103)

• Spontaneous (errors in DNA replication, aberrant recombination/segregation, reactive metabolic products, transposable elements, depurination, deamination, tautomeric shift)
• Induced (physical agents like radiation; chemical agents like mutagens)

Polymorphisms (Page 104)

• Polymorphisms are variations in DNA sequences that are common in a population.
• Includes variations in blood type, sexual dimorphism, etc
• SNPs (single nucleotide polymorphisms) are common types of polymorphisms