ADL-2-the genetic code

Translation

The synthesis of every protein molecule in a cell directed by an mRNA copied from DNA; includes information-transfer and chemical processes.

Translation Direction

mRNA is read 5′→3′ and the polypeptide is synthesized from the amino (N) to carboxyl (C) end.

Genetic Code

Describes correspondence between mRNA nucleotide sequences and the amino acid sequence of resulting polypeptides.

tRNA

Adaptor molecules that interpret mRNA; each has an anticodon complementary to an mRNA codon.

Triplet Code

Groups of three mRNA nucleotides (codons) correspond to one amino acid; 64 codons specify 20 amino acids

Third-Base Wobble

Flexibility in base pairing at the third codon position allowing fewer tRNAs to recognize multiple codons for the same amino acid.

Isoaccepting tRNAs

Different tRNAs that carry the same amino acid but have different anticodons.

Nonoverlapping Code

Each mRNA nucleotide is read once; supported by single-nucleotide substitution studies showing one amino acid change per mutation.

Triplet Genetic Code

Established by Crick and colleagues; insertion or deletion of one or two nucleotides causes frameshift

Deciphering the Code

Conducted between 1961–1965; confirmed the triplet nature and universality of the genetic code; Khorana and Nirenberg won Nobel Prizes.

Nirenberg and Matthai Experiment

Poly(U) mRNA produced only phenylalanine

Universality of Genetic Code

Nearly all organisms share the same code

Mutation

A heritable change in DNA sequence; mutations occur randomly and in every generation.

Mutation Frequency

The number of mutational events per gene per replication cycle (prokaryotes) or per gamete per generation (eukaryotes).

Dominant vs Recessive Mutations

Recessive mutations are more common but dominant ones are easier to detect.

Loss-of-Function Mutation

Causes complete gene inactivation (null or knockout).

Hypomorphic Mutation

Reduces gene expression or protein function.

Hypermorphic Mutation

Increases gene expression or protein activity.

Gain-of-Function Mutation

Produces a new or altered gene function (e.g.

Fluctuation Test

Luria and Delbrück showed mutations arise randomly

Point Mutation

Localized change in one or a few DNA base pairs that can alter a single gene product.

Frameshift Mutation

Caused by insertion or deletion of bases not divisible by three

Regulatory Mutation

Alters the level of gene expression without changing protein sequence; affects promoters

Promoter Mutation

Changes consensus nucleotides near transcription start site

Splicing Mutation

Alters splice site sequences

Cryptic Splice Site

A new or competing splice site formed by mutation

Cis-Regulatory Mutation

Affects transcription factor binding regions; can mildly or dramatically alter gene expression; often impact complex traits.

Polymerase Slippage

Occurs during replication of tandem repeats; leads to insertion/deletion and expansion diseases.

Trinucleotide Repeat Disorder

Caused by excessive repeat expansion within a gene (e.g.

Transposable Elements (TEs)

DNA sequences that move within the genome via enzyme-driven transposition

Barbara McClintock

Discovered mobile genetic elements in maize; awarded the 1983 Nobel Prize in Physiology or Medicine.

Transposase

Enzyme enabling DNA transposon movement; encoded by some transposable elements.

DNA Transposon

Moves by cut-and-paste mechanism; creates target-site duplications and has inverted repeats.

Retrotransposon (LTR)

Copies via RNA intermediate using reverse transcriptase; contains long terminal repeats (LTRs).

Non-LTR Retrotransposon

Includes LINEs and SINEs; lack LTRs; comprise about one-third of the human genome.

TE Abundance

~45% of human genome derived from transposable elements; most are inactive remnants.

TE Effects

TE insertions can disrupt gene function or regulation; in Drosophila

Mutation Detection

Dominant mutations are easier to identify; recessive ones can be studied using homozygotes or specific genetic screens.

Mutation Variability

Mutation frequency differs among species and genes due to replication fidelity

Regulatory Mutation Types

Include promoter

DNA Replication Slippage

Common in repeat sequences

Human Mutation Sources

Each person inherits 1–4 new mutations not shared with parents; paternal age increases mutation rate.

Classes of Transposable Elements

Include DNA transposons

Nobel Recognition for TE Discovery

Barbara McClintock’s maize research revealed genome plasticity and gene expression control by TEs.