Honors Biology Unit 8 ReviewGene Expression and Regulation

Key Concepts and Terminology

• Gene expression process by which genetic information encoded in DNA is converted into functional products (proteins or RNA)
• Transcription synthesis of RNA from a DNA template catalyzed by RNA polymerase
  • Occurs in the nucleus of eukaryotic cells and cytoplasm of prokaryotic cells
• Translation process of decoding mRNA to synthesize polypeptide chains that fold into functional proteins
• Genetic code set of rules that specify the correspondence between codons (triplets of nucleotides) and amino acids
• Promoter region of DNA located upstream of a gene that initiates transcription and determines where RNA polymerase binds
• Enhancers regulatory sequences that can increase the transcription rate of genes
• Silencers regulatory sequences that can decrease or suppress the transcription rate of genes

DNA Structure and Function

• DNA (deoxyribonucleic acid) double-stranded helical molecule that carries genetic information
• Consists of nucleotide monomers each containing a phosphate group, sugar (deoxyribose), and nitrogenous base (adenine, thymine, guanine, or cytosine)
• Complementary base pairing adenine pairs with thymine and guanine pairs with cytosine through hydrogen bonds
• Antiparallel structure two strands run in opposite directions (5' to 3' and 3' to 5')
• DNA packaging in eukaryotes, DNA is tightly coiled around histone proteins to form chromatin, which further condenses into chromosomes
  • Allows large amounts of DNA to fit inside the nucleus
• DNA replication process of making an identical copy of DNA before cell division
  • Ensures genetic information is passed on to daughter cells

Transcription Process

• Transcription first step of gene expression where DNA is used as a template to synthesize complementary RNA
• RNA polymerase enzyme responsible for catalyzing the synthesis of RNA from a DNA template
• Initiation RNA polymerase binds to the promoter region and unwinds the DNA double helix
• Elongation RNA polymerase moves along the DNA template strand (3' to 5') and synthesizes the complementary RNA strand (5' to 3')
  • Ribonucleotides (ATP, UTP, GTP, and CTP) are added to the growing RNA chain
• Termination transcription ends when RNA polymerase reaches a termination sequence, and the newly synthesized RNA is released
• Post-transcriptional modifications in eukaryotes, the primary transcript (pre-mRNA) undergoes modifications before becoming mature mRNA
  • Capping addition of a 7-methylguanosine cap to the 5' end, which protects the mRNA and facilitates translation
  • Polyadenylation addition of a poly(A) tail (multiple adenine nucleotides) to the 3' end, which stabilizes the mRNA
  • Splicing removal of non-coding sequences (introns) and joining of coding sequences (exons) to form the final mRNA

Translation and Protein Synthesis

• Translation process of decoding the genetic information in mRNA to synthesize polypeptide chains
• Ribosomes molecular machines that catalyze the synthesis of proteins by translating mRNA
  • Consist of two subunits (large and small) composed of ribosomal RNA (rRNA) and proteins
• tRNA (transfer RNA) adapter molecules that carry specific amino acids and have anticodons complementary to mRNA codons
• Genetic code set of rules that specify the correspondence between codons (triplets of nucleotides) and amino acids
  • 64 possible codons, 61 of which code for amino acids and 3 are stop codons (UAA, UAG, UGA)
• Initiation translation begins when the small ribosomal subunit binds to the start codon (AUG) on the mRNA with the help of initiation factors
• Elongation tRNA molecules bring amino acids to the ribosome, which are joined together by peptide bonds according to the mRNA sequence
  • Ribosome moves along the mRNA one codon at a time, adding amino acids to the growing polypeptide chain
• Termination translation ends when the ribosome reaches a stop codon (UAA, UAG, or UGA), and the polypeptide chain is released
• Post-translational modifications newly synthesized polypeptide chains may undergo modifications (folding, cleavage, addition of functional groups) to form the final functional protein

Gene Regulation Mechanisms

• Gene regulation control of gene expression that allows cells to respond to environmental changes and maintain homeostasis
• Transcriptional regulation control of gene expression at the level of transcription
  • Involves transcription factors that bind to regulatory sequences (promoters, enhancers, silencers) and influence RNA polymerase activity
• Post-transcriptional regulation control of gene expression after transcription but before translation
  • Includes mRNA processing (capping, polyadenylation, splicing), mRNA stability, and mRNA transport
• Translational regulation control of gene expression at the level of translation
  • Involves factors that influence ribosome binding, translation initiation, and translation efficiency
• Post-translational regulation control of gene expression after translation
  • Includes protein modifications (phosphorylation, glycosylation, ubiquitination) and protein degradation
• Feedback loops regulatory mechanisms that allow cells to maintain stable levels of gene products
  • Negative feedback loops decrease gene expression when the product accumulates, while positive feedback loops increase gene expression

Epigenetics and Gene Expression

• Epigenetics study of heritable changes in gene expression that do not involve alterations to the DNA sequence
• DNA methylation addition of methyl groups to cytosine bases, which can silence gene expression
  • Occurs predominantly at CpG dinucleotides and is catalyzed by DNA methyltransferases (DNMTs)
• Histone modifications post-translational modifications of histone proteins (acetylation, methylation, phosphorylation) that can influence chromatin structure and gene expression
  • Histone acetyltransferases (HATs) add acetyl groups, while histone deacetylases (HDACs) remove them
  • Histone methyltransferases (HMTs) add methyl groups, while histone demethylases (HDMs) remove them
• Chromatin remodeling dynamic changes in chromatin structure that can expose or conceal regulatory sequences and influence gene expression
  • ATP-dependent chromatin remodeling complexes (SWI/SNF) can slide or evict nucleosomes to alter chromatin accessibility
• Epigenetic inheritance transmission of epigenetic marks across generations, which can influence gene expression patterns in offspring
  • Examples include genomic imprinting (parent-of-origin-specific gene expression) and transgenerational epigenetic inheritance

Genetic Mutations and Their Effects

• Mutations changes in the DNA sequence that can alter gene function and expression
• Point mutations single nucleotide changes that can be substitutions (one base replaced by another), insertions (extra base added), or deletions (base removed)
  • Silent mutations do not change the amino acid sequence due to the redundancy of the genetic code
  • Missense mutations change one amino acid to another, which may or may not affect protein function
  • Nonsense mutations introduce a premature stop codon, leading to truncated proteins
• Frameshift mutations insertions or deletions that shift the reading frame, altering the amino acid sequence and often introducing premature stop codons
• Chromosomal mutations large-scale changes in chromosome structure or number
  • Deletions loss of a chromosomal segment
  • Duplications extra copies of a chromosomal segment
  • Inversions reversal of a chromosomal segment
  • Translocations exchange of chromosomal segments between non-homologous chromosomes
• Mutagens factors that can increase the rate of mutations (UV radiation, chemicals, viruses)
• DNA repair mechanisms cellular processes that detect and correct DNA damage and mutations
  • Examples include base excision repair, nucleotide excision repair, and mismatch repair

Real-World Applications and Research

• Genetic engineering deliberate modification of an organism's genome using biotechnology techniques
  • Recombinant DNA technology insertion of foreign DNA into a host organism to produce desired proteins (insulin, growth hormone)
  • CRISPR-Cas9 gene editing tool that allows precise editing of DNA sequences by creating targeted double-strand breaks
• Gene therapy treatment of genetic disorders by introducing functional copies of genes into cells
  • Ex vivo gene therapy cells are removed, modified, and returned to the patient
  • In vivo gene therapy genes are directly delivered to target tissues using viral vectors or nanoparticles
• Personalized medicine tailoring medical treatments to an individual's genetic profile to optimize efficacy and minimize side effects
  • Pharmacogenomics study of how genetic variations influence drug response and toxicity
• Cancer research understanding the genetic and epigenetic alterations that contribute to cancer development and progression
  • Oncogenes genes that, when mutated or overexpressed, can promote cancer growth (RAS, MYC)
  • Tumor suppressor genes genes that normally regulate cell growth and division, but when mutated or silenced, can lead to cancer (p53, RB)
• Stem cell research study of cells that have the ability to self-renew and differentiate into specialized cell types
  • Embryonic stem cells pluripotent cells derived from early-stage embryos that can give rise to all cell types in the body
  • Induced pluripotent stem cells (iPSCs) adult cells reprogrammed to a pluripotent state by introducing specific transcription factors
  • Potential applications include regenerative medicine, disease modeling, and drug screening