Central Dogma: Replication, Transcription, Translation

• The central dogma describes the flow of genetic information: DNA → RNA → Protein
• It includes replication, transcription, and translation

DNA Replication

• Occurs in the nucleus
• Produces an exact copy of DNA before cell division

Key Enzymes and Proteins in DNA Replication

• Helicase unzips DNA strands by breaking hydrogen bonds
• Topoisomerase relieves strain ahead of the replication fork
• Single-strand binding proteins (SSBs) prevent DNA strands from reannealing
• Primase adds RNA primers to initiate replication
• DNA polymerase synthesizes new DNA strands, adding nucleotides in the 5' to 3' direction
• Ligase seals gaps in the lagging strand, specifically Okazaki fragments

Key Features in DNA Replication

• The leading strand is synthesized continuously
• The lagging strand is synthesized discontinuously in Okazaki fragments
• Semi-conservative replication results in each new DNA molecule having one old and one new strand

Transcription

• Occurs in the nucleus
• Converts DNA into messenger RNA (mRNA)

Key Enzymes and Steps in Transcription

• Initiation happens when RNA polymerase binds to the promoter region (e.g., TATA box)
• Elongation sees RNA polymerase synthesize pre-mRNA in the 5' to 3' direction
• Termination occurs when transcription stops at the terminator sequence

Post-Transcriptional Modifications (in Eukaryotes)

• A 5' cap (modified guanine) protects mRNA from degradation
• A poly-A tail (3' end) stabilizes mRNA for transport
• Splicing by spliceosome removes introns (non-coding regions) and joins exons (coding regions)

Translation

• Occurs in the ribosome
• Converts mRNA into a polypeptide (protein)

Key Components in Translation

• mRNA carries codons (3-base sequences)
• tRNA has anticodons that match mRNA codons and carries amino acids
• A ribosome, composed of rRNA and proteins, is the site of protein synthesis

Stages of Translation

• During initiation, a ribosome assembles around mRNA, and the start codon AUG (methionine) is recognized
• During elongation, tRNA brings amino acids, and peptide bonds form between them
• During termination, a stop codon (UAA, UAG, UGA) is reached, and release factors free the polypeptide

Post-translational modifications

• Folding is aided by chaperone proteins
• Cleavage of signal peptides can occur
• Addition of functional groups like phosphorylation or glycosylation can occur

Genetic Code Features

• The triplet code means three nucleotide bases (codon) code for one amino acid
• The genetic code is redundant/degenerate, as multiple codons can code for the same amino acid
• The genetic code is universal, used by almost all living organisms
• The start codon is AUG (methionine)
• The stop codons are UAA, UAG, and UGA, and add no amino acid

Mutations

• Point mutations are single nucleotide changes that can be silent, missense, or nonsense
• Silent mutations cause no change in the amino acid sequence
• Missense mutations change one amino acid
• Nonsense mutations create a stop codon, shortening the protein
• Frameshift mutations are insertions or deletions that alter the reading frame, potentially leading to drastic changes in the protein

Genes and Alleles Definitions

• A gene is a segment of DNA that codes for a protein or trait
• An allele is a different version of a gene (e.g., dominant A or recessive a)
• A locus is the specific location of a gene on a chromosome
• Homozygous means two identical alleles (AA or aa)
• Heterozygous means two different alleles (Aa)

Genetic Inheritance Definitions

• Genotype is the genetic makeup (e.g., AA, Aa, or aa)
• Phenotype is the physical expression of a trait (e.g., blue eyes, tall height)
• A dominant allele is expressed even if only one copy is present (A)
• A recessive allele is expressed only if two copies are present (aa)

Mendelian Inheritance (Gregor Mendel's Laws)

• The law of segregation says each individual has two alleles but only one is passed to offspring, during meiosis
• The law of Independent assortment says genes for different traits are inherited independently if they are on different chromosomes
• The law of dominance says that if an individual has a dominant allele, it will be expressed over the recessive allele

Types of Genetic Crosses

• Monohybrid cross (Aa x Aa) yields a genotypic ratio of 1 AA:2 Aa: 1 aa and a phenotypic ratio of 3 dominant: 1 recessive
• Dihybrid cross (AaBb × AaBb) yields a genotypic ratio of 9:3:3:1 (if genes assort independently) and a phenotypic ratio of 9:3:3:1

Types of Non-Mendelian Inheritance

• Incomplete dominance is blending of traits (e.g., red × white → pink)
• Codominance means both alleles are expressed equally (e.g., blood type AB)
• Multiple alleles means more than two alleles exist (e.g., ABO blood type)
• Polygenic inheritance means traits are controlled by multiple genes (e.g., height, skin color)
• Sex-linked traits are genes located on X or Y chromosomes (e.g., hemophilia, color blindness)

The central dogma outlines the flow of genetic information: DNA to RNA to protein. DNA replication in the nucleus produces exact DNA copies using enzymes like helicase and DNA polymerase. Transcription is the next step in the central dogma.