DNA Mutation Reviewer

DNA Mutation Reviewer

MLS 420 | Molecular Biology

CENTRAL DOGMA

DNA → (Transcription) → mRNA → (Translation) → Protein

• Transcription – occurs in the nucleus; DNA → mRNA

• Translation – occurs in the ribosome/cytoplasm; mRNA → protein

• Sense strand runs 5' to 3'; Anti-sense strand runs 3' to 5'

• mRNA follows the anti-sense (template) strand and has the same sequence as the sense strand

• New strands are always synthesized 5' to 3' because nucleotides are added at the 3' hydroxyl group

THE GENETIC CODE

• 64 total codons, but only 61 are read by tRNA (3 are stop codons)

• Stop codons: UAA, UAG, UGA

• Only 20 amino acids exist because of the Wobble Hypothesis (Francis Crick)

• The first two codon positions always follow standard base pairing; the third position can "wobble" (non-Watson-Crick pairing)

• tRNA carries the anti-codon (3'→5'); mRNA carries the codon (5'→3')

• rRNA aligns and verifies codon-anticodon matching

INTRODUCTION TO DNA MUTATION

A mutation is any change in the normal DNA sequence — substitution, deletion, or insertion.

Two Sources of Mutation

A. Spontaneous Mutation – naturally occurring

1. Tautomeric shift – change in chemical structure of a base makes it unrecognizable to its pair (e.g., G changes → thymine pairs with it instead of cytosine)

2. Depurination – 10,000 purines (A, G) are removed per 22-hour cell cycle via interrupted glycosidic bonds

3. Deamination – amino group removed from cytosine → becomes uracil → G replaced by A

4. Oxidative stress – superoxide radicals/H₂O₂ destroy phosphodiester bonds

B. Induced Mutation (Mutagenesis) – caused by external factors

1. Base replacement (Base analogs) – chemicals with similar structure replace nitrogenous bases (e.g., bromouracil ≈ guanine; prone to tautomeric shift)

2. Base damage – base is physically destroyed; acts like a stop codon. Most common cause: UV radiation

3. Base alteration – base is chemically modified (e.g., EMS adds ethyl group to guanine → unrecognized by cytosine)

IMPORTANCE OF MUTATION

• Major source of genetic variation (drives evolution)

• Can be deleterious or advantageous

• Germ cell mutations → heritable genetic disorders

• Somatic cell mutations → acquired diseases (e.g., cancer)

• Examples of advantageous mutations: HIV resistance, Duffy-negative phenotype (resistance to P. vivax), heterochromia

TYPES OF MUTATION

A. GENE MUTATION (least impact — affects only a small segment)

Mechanisms:

• Substitution (Point Mutation) – one base replaced by another

• Deletion – removal of a base

• Insertion – addition of a base

• Indel – umbrella term for insertion or deletion

Types of Substitution by Structure:

Types of Point Mutation by Function:

Types of Frameshift Mutation (Indels):

• Deletion or Insertion of 1–2 nucleotides → shifts the entire reading frame → wrong amino acids from that point on → abnormal/nonfunctional protein

• If 3 bases (one full codon) are inserted/deleted → no frameshift, just addition/loss of one amino acid

B. CHROMOSOME MUTATION (larger impact — millions of base pairs affected)

• Terminal deletion – end of chromosome deleted

• Interstitial deletion – internal segment deleted

• Paracentric inversion – inversion without centromere

• Pericentric inversion – inversion includes centromere

C. GENOME MUTATION (affects chromosome number)

Euploid = normal chromosome number = 46 chromosomes (23 pairs) = diploid (2n)

Aneuploidy – abnormal number of individual chromosomes:

• Monosomy (2n – 1) – one chromosome has no pair

• Trisomy (2n + 1) – one chromosome has three copies → Best example: Down syndrome (Trisomy 21)

Polyploidy – more than two full sets of chromosomes; pathologic in humans

• Triploid (3n), Tetraploid (4n), etc.

• More ploids = larger organism (best example: plants — can regrow even when cut)

D. OTHER TYPES OF MUTATIONS

• Trinucleotide repeat expansion – repeated codons cause overproduction of the same amino acid; entire frame expands

• Extensive insertions & deletions – large-scale indels (beyond single-base changes)

• Major chromosomal rearrangements – two or more chromosome mutation types occurring simultaneously (e.g., deletion + duplication, translocation + insertion)

QUICK SUMMARY TABLE

Reviewer based on MLS 420 Lecture by Mary Mae Angela O. Dela Peña, RMT | BSMLS 3F