How Genes Work: The Central Dogma, Genetic Code, and Mutations

Chapter 16: How Genes Work

Overview

This chapter explores the molecular basis of gene function, focusing on how genetic information flows from DNA to RNA to proteins. It covers foundational experiments, the central dogma of molecular biology, the genetic code, and the consequences of mutations.

What Do Genes Do?

Beadle and Tatum's Experiments

Beadle and Tatum investigated gene function by creating defective genes and observing their effects on phenotype. Their work with bread mold (Neurospora crassa) led to the concept that genes direct the synthesis of specific enzymes.

• Null or loss-of-function alleles: Mutant alleles that do not produce functional products.

• One-gene, one-enzyme hypothesis: Each gene contains information to make one enzyme.

• Genetic screens: Used to identify mutants unable to synthesize certain compounds, revealing defects in single genes.

One-Gene, One-Polypeptide Hypothesis

Further research showed that most genes contain instructions for making proteins, not just enzymes. The hypothesis evolved to "one-gene, one-polypeptide."

• Polypeptide: A chain of amino acids; proteins may consist of one or more polypeptides.

The Central Dogma of Molecular Biology

Genetic Information Flow

The central dogma summarizes the flow of genetic information in cells: DNA codes for RNA, which codes for proteins. Genes are stretches of DNA that code for proteins, and the DNA sequence determines the RNA sequence, which in turn determines the amino acid sequence in proteins.

• Transcription: The process of using a DNA template to make complementary RNA.

• Translation: The process of using information in mRNA to synthesize proteins.

Linking Genotypes to Phenotypes

An organism's genotype is determined by the sequence of bases in its DNA, while its phenotype is the product of the proteins it produces. Alleles of the same gene differ in DNA sequence, and the proteins produced by different alleles often differ in their amino acid sequence.

• Genotype: The genetic makeup of an organism.

• Phenotype: The observable traits of an organism, resulting from protein expression.

Modifications to the Central Dogma

Some genes code for RNAs that are not translated into proteins but perform important functions. In certain viruses, information can flow from RNA back to DNA via reverse transcriptase.

• Reverse transcriptase: An enzyme that synthesizes DNA from an RNA template.

The Genetic Code

Structure and Function

The genetic code specifies how a sequence of nucleotides codes for a sequence of amino acids. Each "word" in the code is a triplet of bases, known as a codon.

• Codon: A group of three bases that specifies a particular amino acid.

• Triplet code: The three-base code that is the minimum required to specify the 20 amino acids.

Cracking the Genetic Code

Nirenberg and Matthaei synthesized RNAs composed of single types of ribonucleotides and discovered that the UUU triplet codes for phenylalanine. Nirenberg and Leder later determined which codon coded for each amino acid, identifying start and stop codons.

• Start codon (AUG): Codes for methionine and signals where protein synthesis starts.

• Stop codons (UAA, UAG, UGA): Signal the end of the protein-coding sequence.

Properties of the Genetic Code

• Redundant: All but two amino acids are encoded by more than one codon.

• Unambiguous: One codon never codes for more than one amino acid.

• Non-overlapping: Codons are read one at a time.

• Nearly universal: All codons specify the same amino acids in all organisms (with few exceptions).

• Conservative: If several codons specify the same amino acid, the first two bases are usually identical.

Applications of the Genetic Code

• Predicting amino acid sequences from DNA sequences.

• Determining mRNA and DNA sequences that could code for a particular sequence of amino acids.

Types and Consequences of Mutation

Definition and Types

A mutation is any permanent change in an organism's DNA, resulting in a modification of its genotype and potentially creating new alleles. Mutations can be classified as point mutations (affecting one or a few bases) or chromosome-level mutations (larger scale).

• Point mutation: A change affecting a single nucleotide or a small number of nucleotides.

• Chromosome-level mutation: Larger changes affecting chromosome structure or number.

Impacts of Point Mutations

• Beneficial mutations: Increase fitness (ability to survive and reproduce).

• Neutral mutations: Do not affect fitness.

• Deleterious mutations: Decrease fitness.

• Most point mutations are neutral or deleterious.

• Some mutations outside coding regions can affect phenotype by altering gene expression.

Point Mutations That Alter Codons & Consequences

Mutation Type	Supplement Type	Growth
arg1	None	No growth
arg1	Ornithine only	Growth
arg2	Citrulline only	Growth
arg3	Arginine only	Growth

Additional info: Table recreated from experimental results showing how supplementation with pathway intermediates can rescue growth in mutants lacking specific enzymes.

Key Equations

Central Dogma:

$\text{DNA} \rightarrow \text{RNA} \rightarrow \text{Protein}$

Codon-Amino Acid Relationship:

$\text{Codon} = \text{Three nucleotides} \rightarrow \text{One amino acid}$