Advanced high school / Natural Organic Compounds and Polymers 3 / 6

Nucleic Acids and DNA

Nucleic acids, which carry genetic information, are of two types: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). They are central to the molecular biology revolution of the latter half of the 20th century.

Basic Knowledge

The structural unit of nucleic acids, a nucleotide, = sugar + phosphate + base:
・Sugar: DNA = deoxyribose (no C2'-OH); RNA = ribose (has C2'-OH)
・Phosphate: -PO43-. Phosphodiester bonds (-O-PO2--O-) connect sugars.
・Bases: Purine bases = adenine (A), guanine (G). Pyrimidine bases = cytosine (C), thymine (T, DNA only), uracil (U, RNA only).
DNA double helix (Watson and Crick, 1953): Two strands are antiparallel, and the bases pair through hydrogen bonds:
・A=T (2 hydrogen bonds)
・G≡C (3 hydrogen bonds, stronger)
Chargaff's rule: A=T and G=C (in molar amounts).
Central dogma: DNA → (transcription) → mRNA → (translation) → protein. Genetic code: Three bases (a codon) specify one amino acid; 43=64 combinations × 20 amino acids = considerable redundancy.
Types of RNA: mRNA (messenger RNA, carries genetic information), tRNA (transfer RNA, carries amino acids), and rRNA (ribosomal RNA, a component of ribosomes).

Important Terms
Nucleotide (sugar + phosphate + base; unit of DNA/RNA)
Base pairs A=T, G≡C (shown by the number of hydrogen bonds)
Double helix (DNA; one turn per about 10 bases, width 2 nm)
Central dogma (DNA→RNA→protein)
PCR (polymerase chain reaction) (DNA amplification; testing and forensic science)
Genetic recombination/CRISPR (DNA-editing technologies; medical applications)

Further Study (Principles and Applications)

PCR (polymerase chain reaction): Invented by Mullis in 1983. Using a heat-resistant polymerase (Taq) and primers, it repeatedly performs denaturation, annealing, and extension to amplify a specific region exponentially (2n times). It is essential in forensic DNA analysis, infectious-disease diagnosis (COVID-19 PCR testing), genetic diagnosis, and evolutionary research.
Genetic recombination: DNA is cut with restriction enzymes, joined with ligase, and introduced with a foreign gene. Producing human insulin in E. coli for diabetes treatment, put into practical use in 1982, was a landmark achievement.
CRISPR-Cas9 (Doudna and Charpentier, 2012; Nobel Prize, 2020): A revolutionary technology that can cut and edit specific DNA sequences precisely. Applications include treating genetic diseases (a CRISPR treatment for sickle-cell disease was approved in 2023), crop improvement, and research on reviving extinct species.
mRNA vaccines (put into practical use in 2021; coronavirus vaccines): mRNA encoding a pathogen protein is enclosed in lipid nanoparticles and administered; the body produces the protein and acquires immunity. The 2023 Nobel Prize in Physiology or Medicine was awarded to Kariko and Weissman.

Key Points
  • Nucleotide = sugar + phosphate + base.
  • DNA = deoxyribose + ATGC; RNA = ribose + AUGC.
  • Base pairs A=T (2 hydrogen bonds) and G≡C (3 hydrogen bonds).
  • Double helix (Watson and Crick, 1953).
  • Central dogma: DNA→mRNA→protein.
  • PCR amplifies DNA; CRISPR edits DNA.
  • mRNA vaccines opened a new era of drug discovery.

Points of Caution (Common Confusions and Frequent Errors)

① Differences between DNA and RNA: sugar (deoxyribose/ribose), base (T/U), structure (double helix/mainly single strand), and stability (high/low). ② Remember correctly the number of hydrogen bonds in A=T and G≡C (GC-rich DNA is harder to denature at high temperatures). ③ Chargaff's rule: A%=T% and G%=C%, but the A+T:G+C ratio differs among species (in humans, approximately 60% AT and 40% GC). ④ Telomeres (repeating sequences at chromosome ends) shorten with each cell division and are related to lifespan.

Practice

  1. State three structural differences between DNA and RNA.
  2. In a DNA double strand, A is 20%. Find the percentages of G, C, and T (Chargaff's rule).
  3. Explain the three steps of PCR and why DNA increases exponentially.

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