Nucleic Acids and Genetics Flashcards

Nucleic Acids

Learning Objectives

• Identify groups of nucleotides and their derivatives.

• Distinguish the structures of RNA and DNA.

• Describe replication, transcription, and translation.

• Explain how genes are identified.

Chromosomes

• Chromosomes are composed of nucleic acids: False.

Gregor Mendel

• Father of Genetics.

• First to describe predictable patterns of inheritance.

• Inheritance factors = genes.

• Part of chromosomes.

Nucleic Acids

• Polymers of nucleotides.

• Consist of:

  • N-containing base:

    • Purines (A, G).

    • Pyrimidines (C, U, T).

  • Sugar: Ribose (RNA), 2'-deoxyribose (DNA).

  • Phosphate group.

Purines and Pyrimidines

• Purines:

  • Adenine.

  • Guanine.

• Pyrimidines:

  • Cytosine.

  • Thymine.

  • Uracil.

Nucleic Acids Mnemonic

• PUGA = Purines: Guanine and Adenine

• CUT the PY = Cytosine, Uracil, Thymine: Pyrimidines

Purines & Pyrimidines at Physiological pH

• At physiologic pH, purines & pyrimidines (which are bases) donate or accept protons: False!

Nucleosides

• Purine or pyrimidine + 5-C sugar.

• Purine linked via N9.

• Pyrimidine linked via N1.

  • DNA sugar: 2'-deoxyribose.

  • RNA sugar: Ribose.

Nucleotides

• Nucleotides = nucleosides + 1-3 phosphate groups

• Phosphate group linked via C5' of sugar

• Nucleoside mono/di/triphosphate.

• Examples:

  • Adenosine monophosphate (AMP).

  • Guanosine diphosphate (GDP).

  • Cytidine triphosphate (CTP).

Deoxynucleotides

• What about deoxynucleotides?

Nucleic Acids Mnemonic

• Nucleoside = base + Sugar

• Nucleotide = base + sugar + phosphate

Nucleic Acid Bases, Nucleosides, and Nucleotides

Coenzyme A (CoA)

• Contains Adenosine.

Nicotinamide adenine dinucleotide (NAD)

• Contains Adenosine.

Flavin adenine dinucleotide (FAD)

• Contains Adenosine.

Nucleic Acid Structure

• Phosphodiester bond = linkage between nucleotides

  • 1 phosphate group forms an ester bond with

    • C5'

    • C3'

Nucleic Acid Backbone

• Sugar-phosphate backbone.

• Nucleotide sub-unit.

• Pyrimidine base.

• Purine base.

• 5'-3' phosphodiester bonds.

Nucleic Acid Ends

• 5' end.

• 3' end.

Nucleotides Functions

• Building blocks of DNA/RNA.

• Other functions:

  • Energy transduction.

  • Intracellular signaling.

  • Regulation of enzymes.

DNA

• Double helix.

• 2 polynucleotides linked via hydrogen bonds.

• Watson-Crick model.

• Chargaff's rules.

DNA Chargaff’s Rules

• Amount of A = Amount of T

• Amount of C = Amount of G

• A+G = C+T

• For long-term storage of genetic information.

Base Pairing

• DNA → DNA: A-T, G-C

• DNA → RNA: A-U, T-A, G-C, C-G

Features of DNA

• Antiparallel.

• Right-handed.

• Diameter of helix = 20 Å.

• Completes a turn every 10 base pairs.

• Axial distance = 34 Å.

• Major and minor grooves.

• Sugar-phosphate backbone = helix exterior.

• Base pairs = helix center.

• Base pairs stack on top of each other = solid helix core.

DNA Structure

• One complete turn = 34 Å.

• Distance between base pairs = 3.4 Å.

• Diameter = 20 Å.

DNA Nucleotides

• 32 Nucleotides are shown in the example.

DNA Types

RNA

• Single-stranded.

• Has greater conformational freedom vs. DNA.

• 3D vs regular structure.

• Can base pair with DNA.

• RNA-DNA hybrid double helix.

RNA Structure Differences

• Wider and flatter.

• Diameter = 26Å.

• Helical turn every 11 residues.

• Structural differences d/t 2ʹ OH groups in RNA.

Nucleic Acids Stability

• Stability depends on stacking interactions

• Stacked base pairs do not overlap d/t winding

• Additive

• In DNA: A-T separates more easily than G-C

• G-C base pairs = higher stacking energy

Nucleic Acids - Melting Temperature (Tm)

• Quantifies loss of helical structure in DNA

• ↑Temp

  • Base pairs unpack

  • H-bonds break

  • 2 strands begin to separate

Nucleic Acids - Melting = Denaturation

• Recorded as a melting curve

• Increased absorbance of UV (260nm) light

  • Why?

Nucleic Acids - Melting = Denaturation

• Recorded as a melting curve

• Increased absorbance of UV (260nm) light

  • Why?

    • Aromatic bases absorb more light when unstacked

    • Hypochromic effect in base stacking

Nucleic Acids - Renaturation

• When temp is slowly lowered, DNA can renature

• Separated strands can re-form a double helix

• H-bonds reestablish

• Base pairs restack

• Max rate = 20–25°C below Tm

Central Dogma

• Separated DNA strands Direct the synthesis of complementary strands

• Generates 2 identical double-stranded molecs

• Replicated info for each new generation

The Central Dogma of Molecular Biology

• Replication: DNA -> DNA

• Transcription: DNA -> RNA

• Translation: RNA -> Protein

DNA Replication

• Chromosome replicates

• Chromatids separate during cell division

Mitosis

• Result: 2 daughters cells genetically identical to the parent cell

• Standard for unicellular organisms and for the cells within multicellular organisms.

Mitosis Stages

• Parent cell with 6 chromosomes

• DNA replicates

• Chromosomes line up

• Sister chromatids separate

• Cell splits

• Two daughter cells, each with 6 chromosomes

Mitosis Mnemonic

• Prophase = Prepare

• Metaphase = Middle

• Anaphase = Apart/Away

• Telophase = The End

Diploid Cells

• In animals that reproduce sexually, virtually all the cells are diploid: True!

Meiosis

• In animals that reproduce sexually, virtually all the cells are diploid

• Diploid = 2 sets of chromosomes

  • 1 set from each parent

• Animals have specialized cells in ovaries/testes

  • Generate gametes

• Haploid = 1 set of chromosomes

Meiosis - Fertilization

• 2 haploid gametes

  • 1 from each parent

• 2 haploid gametes = new diploid organism

Stages of Meiosis

• Diploid cell with 6 chromosomes

• DNA replicates

• Homologous chromosomes form pairs

• Homologous chromosomes separate, and cell splits

• Sister chromatid's separate, and cells split

• Two haploid cells with replicated chromosomes

• Four haploid gametes, each with 3 chromosomes

• Homologous = same genes but slightly different DNA sequences

Mendelian Inheritance

• Punnett square showing inheritance patterns from parents with Aa alleles.

Non-Mendelian Inheritance

• Incomplete Dominance

  • Neither allele is completely dominant

  • Blending of traits

  • e.g. Red flower (RR) + White flower (WW) → Pink flower (RW)

• Codominance

  • Both alleles are fully expressed

  • e.g. AB blood type

Genome

• Organism's complete set of genetic information

• May comprise several hundred to perhaps 35,000 genes.

DNA Transcription

• 1 strand of DNA used as template to make RNA

• RNA polymerase reads this strand and builds a matching RNA strand

• RNA strand is complementary to the template (noncoding) strand

• Template DNA: 3′-TAC GGT AAG-5′

• RNA: 5′-AUG CCA UUC-3′

DNA Transcription strands

• Coding strand (nontemplate).

• Noncoding strand (template).

DNA Transcription - messenger RNA (mRNA)

• Transcribed RNA = messenger RNA (mRNA)

• Carries the same genetic message as the gene

DNA Translation

• After mRNA is made from DNA, it goes to a ribosome

• mRNA is translated by a ribosome

• Consists of proteins and ribosomal RNA (rRNA)

• Special molecules called transfer RNA (tRNA)…

  • Carry amino acids

  • Recognize codons in mRNA

DNA Translation Process

• As the ribosome moves along the mRNA….

  • tRNAs match their codons

  • Ribosome connects the amino acids one by one into a chain (a polypeptide, which becomes a protein).

DNA Translation example Process

• Shows the translation of mRNA into a protein sequence (Leucine-Serine-Alanine).

Gene Mutations

• Permanent change in DNA

• Single-nucleotide substitution

• Insertion or deletion of nucleotides

• Rearrangements of chromosomal segments

• e.g. Sickle Cell Disease

Sickle Cell Disease Mutation

• Illustrates the mutation in the gene that causes sickle cell anemia.

Genomics

• Study of an organism's complete set of genes

• Number of genes in the human genome is not known

• In general, the size of the genome and the number of protein-coding genes increases with organismal complexity.

Genomics - Practical Applications

• DNA Barcoding: Identifies species from DNA samples

• Metagenomics: Study of genetic material recovered from environmental samples.

Genomics - Practical Applications

• Personal genomics

  • Direct-to-consumer genetic testing (e.g., 23andMe)

• Transgenic organisms: Engineered to contain foreign DNA

  • Used in agriculture and medicine