T--A--C--A--A--G--T--A--C-- T--T--G--T--T--T--C--T--T--A--A—A A- U –G U U C A –U – G A –A –C A A A – G U U U U U Amino: MET - ALA MET TYR LYS VAL PHE

G instead of C Missense AND NONSENSE T--A--C--A--A--C--T--A--C-- T--T--C--T--T--T--C--T--T--A--A—A A- U –G U U G A –U – G A –A –G A A A – G U U U U U Amino: MET - LEU MET STOP LYS VAL PHE

Deletion: FRAMSHIFT T--A--C--A--A--G--T--A--C-- T--T--G--T--T--T--C--T--T--A--A—A A- U –G U U C A –U – G A –A –C A A A – G U U U U U Amino: MET - ALA MET TYR LYS VAL PHE MUTANT DNA: T--A--C--A—A---T--A--C-- T—T---T--T--T--C--T—TAA – A A U G U U A U C G AAA AGA AUU  MET TYR SER LYS ARG PHE

Genetic Code

Gene Expression: Prokaryotes and Eukaryotes AP Biology Ch 18

s

x

c

Gene  Protein Control Feedback inhibition – enough product is made the system shuts down More product is made when needed The product shuts down the process Gene Expression – genes are only expressed when needed. Often regulated at transcription. Figure 18.20a, b (a) Regulation of enzyme activity Enzyme 1 Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 Regulation of gene expression Feedback inhibition Tryptophan Precursor (b) Regulation of enzyme production Gene 2 Gene 1 Gene 3 Gene 4 Gene 5 –

Gene Expression: Prokaryotes Operon – grouped genes that are transcribed together – code for functionally similar proteins Key Players Promoter – section of DNA where RNA polymerase binds Operator – Controls activation of transcription on off switch between promoter and genes for proteins – structural genes Repressor protein – binds to operator to block RNA polymerase and shut down transcription Turns off the operon Corepressor – keeps the repressor protein on the operator Trp operon Inducer – pulls repressor off the operator Turns on the operon – lactose on the lac operon Regulatory gene – produces the repressor protein Structural genes – code for proteins

Positive and Negative Gene Regulation E. coli prefer to use glucose for energy, they will only use lactose when glucose is in short supply glucose cAMP binds to regulatory protein “CAP” & stimulates gene transcription Positive gene regulation! The cAMP & CAP combination allow RNA polymerase to bind to the promoter sequence more efficiently.] Remember cAMP is regulating the gene expression in the bacteria Negative Repressible: usually on but can be inhibited trp operon, allosteric inhibition, tryptophan present prevents its own production. (anabolic) Inducible: usually off, but can be turned on, an inducer (a specific small molecule, allolactose in the lac operon) inactivates the repressor and allows transcription (catabolic)

                                                       

Eukaryotic Chromosome

Eukaryotic Chromosome Chromosomes – tightly coiled DNA around proteins during cell division Chromatin – loosely packed DNA around proteins Histones – protein which the DNA wraps around Nucleosomes – grouped histones together Heterochromatin – tighter packed chromatin Not transcribing Euchromatin – looser packed chromatin Transcription occurring

Gene Expression: Eukaryotes Cell Differentiation – cell specialization All cells contain the same genes The genes that are expressed determines the type of cell Ex: Skin cell vs. a nerve cell

Chromatin Regulation Histone acetylation – allows transcription factors to bind to DNA allowing transcription to occur Creates loosely packed DNA - euchromatin DNA Methylation – occurs after DNA synthesis has occurred Lower transcription rates One X in females is highly methylated (XX vs XY)

Epigenetic inheritance Not controlled by base sequences. DNA methylation (deactivates one homologous chromosome) may explain abnormal or unexpected DNA expression as is often seen in identical twins. http://images.the-scientist.com/content/images/general/55342-1.jpg

Regulation of Transcription Transcription involves RNA Polymerase and transcription factors RNA polymerase attaches to the promoter (TATA box) sequence to begin transcription Control elements – non coding sequences of DNA where the transcription factors attach

Regulation of Transcription 18_Animations\18_09TranscripInitiation_A Regulation of Transcription 18_Animations\18_09TranscripInitiation_A.swf Enhancer – control element far from a gene or intron Activator – bind to enhancers to turn on transcription of a gene Transcription factors + enhancer + activator + RNA Polymerase = transcription initiation complex Needed for transcription to begin Repressors – inhibit gene expression Turn off transcription Block activators from binding to enhancers

brings the bound activators closer to the promoter. Distal control element Activators Enhancer Promoter Gene TATA box General transcription factors DNA-bending protein Group of Mediator proteins RNA Polymerase II RNA synthesis Transcription Initiation complex Chromatin changes RNA processing degradation mRNA Translation Protein processing and degradation A DNA-bending protein brings the bound activators closer to the promoter. Other transcription factors, mediator proteins, and RNA polymerase are nearby. 2 Activator proteins bind to distal control elements grouped as an enhancer in the DNA. This enhancer has three binding sites. 1 The activators bind to certain general transcription factors and mediator proteins, helping them form an active transcription initiation complex on the promoter. 3

RNA Processing Regulation 18_Animations\18_11RNAProcessing_A.swf Alternative RNA Splicing – different regions of the pre-mRNA serve as introns or exons creating different mRNA strands depending on what is spliced out.

Protein Degradation 18_Animations\18_12ProteinDegradation_A.swf Proteosomes – break apart proteins in to smaller peptide units Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Ubiquitin Protein to be degraded Ubiquinated protein Proteasome and ubiquitin to be recycled Protein fragments (peptides) Protein entering a proteasome

Constantly Active Genes Oncogene – cancer causing gene Proto-oncogene - normal gene that regulates cell division and growth Proto-oncogene  oncogene = cancer Certain viruses can be incorporated into DNA and increase cancer

G Protein & ras gene 18_Animations\18_15bbCellSignaling_A.swf G protein: A protein that binds GTP ( a cellular energy source). GTP transfers its phosphate groups to other molecules and releases energy in the process Crucial in cell signaling a ras gene mutation triggers protein production of a protein that stimulates the cell cycle = cancer http://kph12.myweb.uga.edu/11_6Gprotein.jpg

Human Genome Exons (regions of genes coding for protein, rRNA, tRNA) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory (24%) Unique noncoding DNA (15%) DNA unrelated to (about 15%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5-6%)

Compare and Contrast Gene Regulation in Prokaryotes and Eukaryotes