Chapter 16 Gene Expression and Regulation

Genetic Mutations

any change in a DNA sequence

Spontaneous mutations

Results from DNA copying mistakes

Error during cell division

Induced mutations

Mutagens

Exposure to ionizing radiation,chemicals or infection by certain bacteria or viruses

Genetic Mutations

Provide diversity and variation

occurs at different levels of gene expression

Beast

Feast

Breast

Best

Beats

Point mutations

change of a single nucleotide in the template DNA

affects structure and function leading to the production of an abnormal protein

Mutant Sickle Cell

Has a VAL (valine) instead of a glutamic acid (Glu)

Types of point mutations

Base Pair insertions or deletions (indels)

Base pair substitutions

Silent (Synonymous) Substitutions

Change in a nucleotide without changing an amino acid

Redundancy in amino acid chart

Allows for maintenance of gene without variation to genome

Missense (nonsynonymous) substitution

change in a nucleotide results in a change to the the amino acid

can cause loss of function, new function, more function, less function can be good or bad

Nonsense Substitution

Cause the encoding of a premature stop codon

cause loss of function but can cause new function

Insertion or Deletions (Indels)

Addition or losses of nucleotide pairs in a gene

may produce frameshift mutations

Nucleotide Insertion

refers to the addition of one or more nucleotide bases into a DNA sequence, potentially leading to mutations can cause nonsense but not all the time

Nucleotide Deletions

is a type of mutation that results from the missing of a nucleotide , frameshift causing extensive missense

Indels:In case of threes

nucleotide bases, the addition or deletion of bases does not cause a frameshift, but but one amino acid missing

Somatic Cells 2n

Everything besides sperm and egg

Contain all of the same DNA

Why gene regulation

the control of which genes are expressed dictates whether a cell is a muscle, nerve, or liver cell

Differential gene expression

The patterns that arise in different cells that give rise to a complete organism

Cell Differentiation

Cells undergo a process of specialization in form and function

Gene Regulation Determines

What cell type each cell will differentiate into

patterns and paths of gene expression during development

gene expression patterns in mature cells

Regulation maintains efficiency

Save time, energy, and space

essential for development, differentiation and environmental response

Prokaryotic Regulation of Gene Expression

Organized in a circular chromosome within cytoplasm

Transcription and Translation occur simultaneously

Regulation in a Prokaryotic gene

Regulation is restricted to a transcriptional level

Operons

Prokaryotes organize their genes into sections within their genome

clusters of genes that are transcribed together using one common promoter and operator

Repressors

suppress transcription and gene expression

Activators

Enhance transcription and gene expression

Inducers

suppress or enhance transcription and gene expression depending on current needs of each cell

The TRP (tryptophan) operon

repressible operon

regulated by a repressor

expression is dependent on the cells internal environment

ON when TRP is low

OFF when TRP is high

TRP binds repressor > repressor binds operator

Lac Operon

Inducible operon

Regulated by inducers that either activate or repress transcription

dependent on the cells internal environment

What 2 inducers regulate lac operon

Allolactose and Catobolite activator protein(CAP)

Repressing Inducer lac operon

No lactose : repressor binds operator→no transcription

Lactose Present: allolactose binds repressor → some transcription

Activating Inducer - lac operon

Low Glucose- high cAMP→ binds CAP → enhances transcription

Catabolite Activator Protein (CAP)

an activation inducer for the lac operon

binds with cAMP to form a complex, complex then bind to an activation sequence upstream of the operon

Eukaryotic Regulation of Gene Expression

Physical separation of transcription and translation

Trscription and RNA processing occur in the nucleus

Translation and post translational modification occur mostly in the cytoplasm

Gene expression is regulated at many levels

Epigenetic, transcriptional, nuclear shuttling, post transcriptional, translational and post translational

Epigenetic Stage

chemical modification during DNA packaging

Inhertible

No change in DNA sequence

Accessibility

Long term or short term

nucleus

Transcriptional Stage

initiation and rate regulation

Promoters ,Enhancers , and repressors

nucleus

Post transcriptional stage

alternative splicing

mRNA processing

mRNA stability

nucleus

translation stage

imitation regulation

cytoplasm

post translational stage

protein modification

protein degradation

cytoplasm

Epigenetic Regulation

controls the frequency rate or extent of gene regulation

inheritable

no change in DNA sequence

chromatin structure regulation

chemical modification of histone tails → gene expression

Transcription level regulation

Achieved through the regulation of RNA polymerase recruitment

TFs binds to promoters/enhancers

Transcription factors

RNA polymerase requires this to initiate transcription

control binding and initiation of transcription

can function as regulators and activators

bind to promoter sequences and regulatory sequences

Enhancers

short regulatory sequence that promotes transcription by binding to activator proteins

Silencers

Short regulatory sequences that decrease transcription by binding to repressor proteins

proximal CE

Regulatory sequences of DNA found close to promoters of the genes they help regulate

Buying specific activator or repressor proteins to affect the rate of transcription

Distal CE

Found far from the jeans they helped to regulate very specific

Post transcriptional regulation

RNA transcripts must be processed in the nucleus and into mature form before heading into the cytoplasm for translation to begin

5’cap and 3’ tail and alternative splicing,( excising intron, and joining Exon's)

Untranslated regions of mRNAs(UTR's)

Found on both the five prime and the three prime ends of mature mRNA

Provide binding sites for specific proteins that increase RNA stability (inc or dec)

MicroRNA's(miRNAs)

Short RNA molecules 21 to 24 nucleotides that recognize a specific sequence on a mature mRNA

Interact with a special protein called RNA inducing silencing complex (RISC)

miRNA and RISC

complex binds and degrades targeted mRNA

Initiation complex

Translation is regulated and controlled by proteins that bind and initiate the start of the process

Eukaryotic initiation factor-2 (eIF-2)

1st portion to bind the small sub unit of the ribosomes and form the complex

Methionine initiator tRNA binds mRNA and binds the complex above

Phosphate and eIF-2 are released and the large ribosomal subunit binds

translation occurs

Chemical modifications affect protein activity

Protiens can be chemically modified add or remove

regulate protein activity or the length of time they exist in the cell

Chemical modifications can alter what?

All changes in expression of various genes

Epigenetic accessibility

Transcription

mRNA stability

Translation

Cancer

results from genetic changes that affect cell cycle control

Gene regulation systems that go wrong during cancer

Embryonic development

Cell cycle

DNA repair

Proto-oncogenes

Normal cellular genes that code for proteins that control, normal cell growth and division

Positive cell cycle regulators

oncogenes

Abnormal cancer, causing versions of proto-oncogenes(mutations )

Alter transcriptional activity of a gene that controls cell growth

Tumor Supressor Genes

Encode proteins that inhibit abnormal cell division

Function to prevent excessive or inappropriate cell growth

Negative cell cycle regulators

cancer Inheritance and Predisposition

Individuals who inherit a ancient oncogene or tumor suppressor allele have an increased risk of developing certain types of cancer

mutagens

Carcinogens can cause damage and mutations to your DNA

Certain Viruses

These viruses promote cancer by integrating their own DNA into a cells genome

Cause genetic changes on host gene or incorporates oncogene from virus into host genome

Circadian Rhythm

Endogenously generated can be affected by eternal cues like sun and temp

Clear pattern of Braly activity, hormone production, cell regulation, and other biological activities linked to the daily cycle