Decoding genetic information

What are mutations:

• Changes in WHAT sequence (DNA and RNA)

• Can be WHAT (WHAT) or not WHAT (WHAT)

• Changes can be small (WHAT level) or large (WHAT)

• Altered gene sequence can change the WHAT sequence of the polypeptide resulting in WHAT in the phenotypes

What are mutations:

• Changes in NUCLEIC ACID sequence (DNA and RNA)

• Can be INHERITED (GERMLINE) or NOT INHERITED (SOMATIC)

• Changes can be small (GENE level) or large (CHROMOSOMAL)

• Altered gene sequence can change the AMINO ACID sequence of the polypeptide resulting in VARIATION in the phenotypes

Effect on phenotypes can be

• WHAT = WHAT

• WHAT = WHAT 

• WHAT = WHAT 

Effect on phenotypes can be

• Harmless = neutral

• Harmful = Deleterious 

• Beneficial = Advantageous  

• Spontaneous mutations are naturally-occurring mutations mainly caused by WHAT errors (1 mutation/1^10 bp of DNA replicated) and spontaneous WHAT

• Include WHAT removed A/G bases and WHAT (losing a group (cytosine to uracil))

• Spontaneous mutations are naturally-occurring mutations mainly caused by REPLICATIONS errors (1 mutation/1^10 bp of DNA replicated) and spontaneous LESIONS

• Include DEPURINATION removed A/G bases and DEAMINATION (losing a group (cytosine to uracil))

Induced Mutations

• Natural (environment) or artificial agents (mutagens) that cause mutations at a rate much higher than WHAT mutations

• Induce mutations by replacing a WHAT, alter a base so it WHAT with another base, or WHAT a base where it can no longer pair with any base

• Base analogs: mimic WHAT and incorporates into DNA (can cause mispairing during DNA replication); e.g. 5-bromouracil:thymine analog that can pair with A or G

• Chemicals that alter base structure to cause WHAT (e.g. alkylating and intercalating agents-benzopyrene)

• WHAT to bases (UV light-thymine dimers, aflatoxin B-apurinic sites)

Induced Mutations

• Natural (environment) or artificial agents (mutagens) that cause mutations at a rate much higher than SPONTANEOUS mutations

• Induce mutations by replacing a BASE, alter a base so it MISPAIRS with another base, or DAMAGE a base where it can no longer pair with any base

• Base analogs: mimic BASES and incorporates into DNA (can cause mispairing during DNA replication); e.g. 5-bromouracil:thymine analog that can pair with A or G

• Chemicals that alter base structure to cause MISPAIRING (e.g. alkylating and intercalating agents-benzopyrene)

• DAMAGE to bases (UV light-thymine dimers, aflatoxin B-apurinic sites)

Germline mutation occur in WHAT, and therefore, are WHAT

Germline mutation occur in GAMETE FORMATION, and therefore, are HERITABLE

Example: sex-influenced trait – autosomal dominant trait
that is dependent on sex (males express the trait in
heterozygotes but females do not)

Somatic mutations:

• Somatic mutations occurs in a WHAT cell (any cell that first experiences the mutation) and all sequential WHAT cells express the mutation

• Somatic mutations are expressed as WHAT (size depends on time of mutation)

• Cancer tumors are an example of somatic mutations

Somatic mutations:

• Somatic mutations occurs in a PROGENITOR cell (any cell that first experiences the mutation) and all sequential DAUGHTER cells express the mutation

• Somatic mutations are expressed as SECTORS (size depends on time of mutation)

• Cancer tumors are an example of somatic mutations

Point mutation 

A change at a SINGLE BASE on the DNA 

What are all the point mutations:

• WHAT

What are the frameshift mutations

• WHAT

• WHAT

What are all the point mutations:

• Base substitution

What are the frameshift mutations

• Insertion

• Deletion

Base substitution

Original nucleotide becomes a different nucleotide 

Insertion

A nucleotide is ADDED to the double helix 

Deletion 

A nucleotide is REMOVED from the double helix 

• Point mutation 

• Base substitution

• Insertion

• Deletion

These mutations all occur on WHAT DNA strand

• Point mutation 

• Base substitution

• Insertion

• Deletion

These mutations all occur on BOTH DNA strand

Types of base substitutions

• WHAT 

• WHAT 

Types of base substitutions

• Transitions  

• Transversions 

Transition

A purine is swapped for a purine or a pyrimidine for a pyrimidine 

Transversions

A purine to a pyrimidine or a pyrimidine to a purine 

Silent (synonymous) mutation

Codon change does NOT change the amino acid due to degeneracy of the genetic code

Missense (non-synonymous) mutations

Codon change causes a CHANGE in the amino acid sequence 

Nonsense mutations

Sense codon is changed to a nonsense (STOP) codon, resulting in a TRUNCATED polypeptide

• Nonsense mutations

• Missense (non-synonymous) mutations

• Silent (synonymous) mutation

These are all WHAT mutations 

• Nonsense mutations

• Missense (non-synonymous) mutations

• Silent (synonymous) mutation

These are all BASE PAIR mutations 

Frameshift mutation

Changes the reading frame of the mRNA due to INSERTION or DELETION of nucleotides

Sickle cell anemia:

• A base substitution point mutation in the WHAT gene

• The WHAT results in a WHAT mutation that changes the 6th amino acid from glutamic acid (Glu) to valine (Val)

• In low oxygen environments, the beta subunit causes hemoglobin molecules to polymerize into WHAT that alter the shape of WHAT

• Leads to deficient gas exchange, clogged arteries (pain), circulatory problems, higher risk of heart attack and stroke

Sickle cell anemia:

• A base substitution point mutation in the BETA HEMOGLOBIN gene

• The TRANSVERSION results in a MISSENSE mutation that changes the 6th amino acid from glutamic acid (Glu) to valine (Val)

• In low oxygen environments, the beta subunit causes hemoglobin molecules to polymerize into LONG FIBERS that alter the shape of RBCs

• Leads to deficient gas exchange, clogged arteries (pain), circulatory problems, higher risk of heart attack and stroke

What are large scale chromosomal mutations

• WHAT 

• WHAT 

• WHAT 

• WHAT 

What are large scale chromosomal mutations

• Deletion  

• Duplication/Amplification  

• Translocations 

• Inversions  

Deletion

Loss of GENES

Duplication/Amplification

Increasing dosage of genes (Main way to evolution)

Translocations 

Interchange of genetic parts from NON-HOMOLOGOUS chromosomes (not crossing over) 

Inversions 

Reversing orientation of a segment of the chromosome 

Allele

One of many different forms of a GENE (sequence variations) which can cause DIFFERENT PHENOTYPES 

Wildtype allele

“Normal” form of the gene found in nature or the standard laboratory strain of a model organism

Gain of function 

Mutations that ENHANCE gene function/expression 

Loss of function 

Mutations that REDUCE/ELIMINATE gene function/expression 

The eukaryotic cell cycle

• The cell cycle is an ordered set of processes by which one cell WHAT and WHAT into two WHAT cells 

The eukaryotic cell cycle

• The cell cycle is an ordered set of processes by which one cell GROWS and DIVIDES into two DAUGHTER cells 

The eukaryotic cell cycle

Need to fully replicate WHAT and WHAT and properly segregate them to WHAT cells

The eukaryotic cell cycle

Need to fully replicate DNA and ORGANELLES and properly segregate them to DAUGHTER cells

The eukaryotic cell cycle what all occurs

• G1 and G2 (Gap and growth phase) 

• S phase 

• M phase (mitosis) 

• Cytokinesis 

• G0 phase 

The eukaryotic cell cycle

G1 and G2 (growth and gap phase): WHAT

The eukaryotic cell cycle

G1 and G2 (growth and gap phase): Synthesis of PROTEINS, RNA, metabolites, other than DNA

The eukaryotic cell cycle

S phase: WHAT

The eukaryotic cell cycle

S phase: DNA replication 

The eukaryotic cell cycle

M phase: WHAT

The eukaryotic cell cycle

M phase: NUCLEAR division 

The eukaryotic cell cycle

Cytokinesis: WHAT

The eukaryotic cell cycle

Cytokinesis: CELL division

The eukaryotic cell cycle

G0: WHAT

The eukaryotic cell cycle

G0: Resting phase or quiescence (doesn’t under go mitosis again or under goes in very slowly)

The eukaryotic cell cycle

Most adult human cells are in WHAT either permanently (WHAT or WHAT cells) or semi permanently (WHAT cells reenter G1 during injury) 

The eukaryotic cell cycle

Most adult human cells are in G0 either permanently (MUSCLE or NERVE cells) or semi permanently (LIVER cells reenter G1 during injury) 

Regulation of eukaryotic cell cycle

• Progression of the cell cycle depends upon activation of a WHAT bound to its regulatory WHAT subunit in each phase of the cell cycle 

• Checkpoints WHAT the cell cycle to allow completion of the event of each phase before proceeding to the next phase 

Regulation of eukaryotic cell cycle

• Progression of the cell cycle depends upon activation of a CYCLIN-DEPENDENT KINASE (CDK) bound to its regulatory CYCLIN subunit in each phase of the cell cycle 

• Checkpoints DELAY the cell cycle to allow completion of the event of each phase before proceeding to the next phase 

What are the the check point to regulation of eukaryotic cell cycle

• WHAT

• WHAT

• WHAT

What are the the check point to regulation of eukaryotic cell cycle

• DNA damage (G1/S) checkpoint 

• DNA replication (G2/M) checkpoint 

• Mitotic spindle (M) checkpoint 

DNA damage (G1/S) checkpoint: WHAT 

DNA damage (G1/S) checkpoint: Is DNA okay for REPLICATION  

DNA replication (G2/M) checkpoint: WHAT 

DNA replication (G2/M) checkpoint: Is DNA fully replicated before mitosis  

Mitotic spindle (M) checkpoint: WHAT

Mitotic spindle (M) checkpoint: Are CHROMOSOMES aligned properly in metaphase

Cancer = WHAT 

Cancer = Uncontrolled cell division  

Cancer is WHAT growth caused by WHAT cell division and is caused by altered WHAT of multiple genes due to WHAT (polygenic disease) 

→ Cells don’t go in the WHAT 

→ cancer = when cell division isn’t WHAT 

→ Gain of function = WHAT 

→ Loss of function = WHAT 

Cancer is MALIGNANT growth caused by UNCONTROLLED cell division and is caused by altered EXPRESSION of multiple genes due to MUTATIONS (polygenic disease) 

→ Cells don’t go in the CHECKPOINT 

→ cancer = when cell division isn’t REGULATED 

→ Gain of function = GO signal 

→ Loss of function = Broken breaks  

Which mutated genes are implicated in cancer:

1. WHAT 

2. WHAT 

3. About 50% of tumors have an inactive WHAT gene and cyclin WHAT and WHAT are often highly expressed in WHAT cancer carcinomas 

4. Each cancer is cause by different WHAT - Difficult to find universal cure 

Which mutated genes are implicated in cancer:

1. Oncogenes (Go)  

2. Tumor supressor genes (breaks)  

3. About 50% of tumors have an inactive p53 gene and cyclin D and E are often highly expressed in BREAST cancer carcinomas 

4. Each cancer is cause by different GENE MUTATIONS - Difficult to find universal cure 

Which mutated genes are implicated in cancer:

Oncogenes = WHAT regulators of the cell cycle (gain-of-function) including WHAT (gene amplification), WHAT alleles (insensitive to inhibition) 

Which mutated genes are implicated in cancer:

Oncogenes = POSITIVE regulators of the cell cycle (gain-of-function) including CYCLIN D/E (gene amplification), cdk4 alleles (insensitive to inhibition) 

Which mutated genes are implicated in cancer:

Tumor supressor genes: WHAT regulators of the cell cycle ( loss of function) including WHAT genes WHAT and WHAT

Which mutated genes are implicated in cancer:

Tumor supressor genes: NEGATIVE regulators of the cell cycle (loss of function) including CHECKPOINT genes p53 and RB

Homologous chromosomes:

• Parental pair of WHAT molecules

• The number and order of WHAT are the same between homologous chromosomes but WHAT can be different

• 2n = WHAT number of DNA molecules

• n = WHAT number of DNA molecules

Homologous chromosomes:

• Parental pair of DNA molecules

• The number and order of GENES are the same between homologous chromosomes but ALLELES can be different

• 2n = DIPLOID number of DNA molecules

• n = HAPLOID number of DNA molecules

DNA replication (S phase)

• Each DNA molecule is replicated WHAT

• Following replication, each DNA molecules exists as a pair of WHAT that are attached at the WHAT

DNA replication (S phase)

• Each DNA molecule is replicated INDEPENDENTLY 

• Following replication, each DNA molecules exists as a pair of SISTER CHROMATIDS that are attached at the CENTROMERE 

DNA replication (S phase)

HOW MANY DNA molecules 

HOW MANY Homologous pairs 

HOW MANY Chromatid

HOW MANY Sister chromatids 

DNA replication (S phase)

1 DNA molecules 

0 Homologous pairs 

1 Chromatid

0 Sister chromatids 

DNA replication (S phase)

HOW MANY DNA molecules 

HOW MANY Homologous pairs 

HOW MANY Chromatid

HOW MANY Sister chromatids 

DNA replication (S phase)

1 DNA molecules 

0 Homologous pairs 

2 Chromatid

1 Sister chromatids 

DNA replication (S phase)

HOW MANY DNA molecules 

HOW MANY Homologous pairs 

HOW MANY Chromatid

HOW MANY Sister chromatids 

DNA replication (S phase)

2 DNA molecules 

1 Homologous pairs 

4 Chromatid

2 Sister chromatids 

DNA replication (S phase)

HOW MANY DNA molecules 

HOW MANY Homologous pairs 

HOW MANY Chromatid

HOW MANY Sister chromatids 

DNA replication (S phase)

4 DNA molecules 

2 Homologous pairs 

8 Chromatid

4 Sister chromatids 

G1 (2n) 

HOW MANY chromosomes (DNA molecules) 

HOW MANY chromatid/chromosomes (per each)

G1 (2n) 

4 chromosomes (DNA molecules) 

1 chromatid/chromosomes 

G2 (2n)

HOW MANY chromosomes (DNA molecules) 

HOW MANY chromatid/chromosomes 

G2 (2n)

4 chromosomes (DNA molecules) 

2 chromatid/chromosomes (per each)

Between G1 and G2

Between G1 and G2

• DNA REPLICATION  

• chromosomes are not VISIBLE 

• CENTRIOLE duplication 

• MITOCHONDRIA duplication 

Prophase (2n) 

HOW MANY chromosomes 

HOW MANY chromatids/chromosomes 

Prophase (2n) 

4 chromosomes 

2 chromatids/chromosomes 

Between G2 and prophase

Between G2 and prophase

• Chromosomes CONDENSE and become VISIBLE

• CENTROSOMES move apart and form MITOTIC SPINDLES

• NUCLEAR ENVELOPE breaks down

Mitotic spindle formation diagram 

Prometaphase (2n)

HOW MANY chromosomes

HOW MANY chromatids/chromosomes

Prometaphase (2n)

4 chromosomes

2 chromatids/chromosomes

Prometaphase

• Centrosomes reach opposite WHAT 

• WHAT microtubules attach to each other 

• WHAT microtubules attach to WHAT proteins at the WHAT 

• Sister chromatids are connected to WHAT 

• Chromosomes start migrating to WHAT 

Prometaphase

• Centrosomes reach opposite POLES 

• NON-KINETOCHORE microtubules attach to each other 

• KINETOCHORE (SPINDLE) microtubules attach to KINETOCHORE proteins at the CENTROMERES 

• Sister chromatids are connected to OPPOSITE POLES 

• Chromosomes start migrating to EQUATOR  

Kinetochore microtubules diagram

Metaphase (2n) 

HOW MANY chromosomes 

HOW MANY chromatids/chromosomes 

Metaphase (2n) 

4 chromosomes 

2 chromatids/chromosomes 

Metaphase 

• All DNA molecules are aligned at the WHAT (WHAT plate) 

• Sister chromatids are attached to WHAT 

Metaphase 

• All DNA molecules are aligned at the EQUATOR (METAPHASE plate) 

• Sister chromatids are attached to OPPOSITE POLES  

Anaphase (4n)

HOW MANY chromosomes 

HOW MANY chromatids/chromosomes (per DNA molecule) 

Anaphase (4n)

8 chromosomes 

1 chromatids/chromosomes (per DNA molecule) 

Anaphase (4n)

• Sister chromatids are WHAT 

• Chromatids are now WHAT DNA molecules (chromosomes) 

• Cell is WHAT 

• Kinetochore microtubules WHAT (WHAT) 

• Non-kinetochore microtubules WHAT 

Anaphase (4n)

• Sister chromatids are SEPARATE 

• Chromatids are now INDEPENDENT DNA molecules (chromosomes) 

• Cell is TETRAPLOID 

• Kinetochore microtubules DEPOLYMIZE (SHORTEN) 

• Non-kinetochore microtubules LENGTHEN 

Microtubules (de)polymerization diagram

Telophase 4n

HOW MANY chromosomes

HOW MANY chromatid/chromosomes per DNA molecule

Telophase 4n

8 chromosomes

1 chromatid/chromosomes per DNA molecule

G1 2n

HOW MANY chromosomes

HOW MANY chromatid/chromosomes per DNA molecule

G1 2n

4 chromosomes

1 chromatid/chromosomes per DNA molecule

From anaphase to telophase

• Chromosomes cluster at OPPOSITE poles and DECONDENSE 

• Nuclear envelope REFORMS 

• Cytokinesis (division of the cell) beings by FURROWING 

From telophase to G1

• Two daughter cells taht are GENETIC DUPLICATES of the parental strand 

Cell cycle in prokaryotes (binary fission)

• Replication beings at the WHAT 

• Bacterial chromosome (template and daughter) is attached to the WHAT 

• Cell WHAT and bacterial chromosomes WHAT 

• Inward growth of plasma membrane and partition assembly of new WHAT, WHAT replicated DNA 

• Produces WHAT 

• Effective because only HOW MANY chromosomes 

• WHAT evolved from this process 

Cell cycle in prokaryotes (binary fission)

• Replication beings at the ORI 

• Bacterial chromosome (template and daughter) is attached to the INNER MEMBRANE  

• Cell ELONGATES and bacterial chromosomes SEPARATE 

• Inward growth of plasma membrane and partition assembly of new CELL WALL, DIVIDING replicated DNA 

• Produces TWO DAUGHTER CELLS  

• Effective because only 1 chromosomes 

• MITOSIS evolved from this process 

Our germ cells contain HOW MANY chromosomes

• We have HOW MANY pairs of homologous chromosomes 

Our germ cells contain 46 chromosomes

• We have 23 pairs of homologous chromosomes 

Reproduction must maintain the WHAT number of chromosomes, so gamete formation separates the WHAT pairs 

• Results in WHAT 

Reproduction must maintain the DIPLOID number of chromosomes, so gamete formation separates the HOMOLOGOUS pairs 

• Results in HAPLOID sperm/ova 

WHAT (WHAT) restores the diploid number in the zygote in a “new” combination of WHAT

FERTILIZATION (SYNGAMY) restores the diploid number in the zygote in a “new” combination of ALLELES

Interphase 

• Germ cells follow a modified cell cycle

- WHAT, WHAT, WHAT, WHAT*

• S phase

- All WHAT DNA molecules are WHAT

- Each DNA molecule exists as a pair of WHAT

• M phase

- First cellular division

     - Generates WHAT 

     - Each DNA molecule exists as a pair of WHAT

- Second cellular division 

     - Generates WHAT 

     - Each with a WHAT copy of each DNA molecule

Interphase 

• Germ cells follow a modified cell cycle

- G1, S, G2, M*

• S phase

- All 46 DNA molecules are REPLICATED

- Each DNA molecule exists as a pair of SISTER CHROMATIDS 

• M phase

- First cellular division

     - Generates HAPLOID CELLS  

     - Each DNA molecule exists as a pair of SISTER CHROMATIDS 

- Second cellular division 

     - Generates HAPLOID GAMETES  

     - Each with a SINGLE copy of each DNA molecule

Meiosis 1: Prophase 1

• Just like prophase in mitosis except WHAT 

• Non-sister chromatids of homologous chromosomes are attached by a protein structure called the WHAT 

• Pieces of the WHAT are exchanged by “breakage and reunion” process called WHAT 

Meiosis 1: Prophase 1

• Just like prophase in mitosis except HOMOLOGOUS CHROMOSOMES synapse to form TETRADS 

• Non-sister chromatids of homologous chromosomes are attached by a protein structure called the SYNAPTONEMAL COMPLEX 

• Pieces of the NON-SISTER CHROMATIDS are exchanged by “breakage and reunion” process called HOMOLOGOUS RECOMBINATION  

Recombination in eukaryotes (swapping only the alleles) 

• Homologous chromosomes align with each other during WHAT and exchange of sections of WHAT occur by WHAT

• Precise breakages of each strand 

• Equal exchange of WHAT material 

• Repair of breakage after WHAT exchange 

• Genetic exchange can involve large sections of the homologous chromosomes creating new chromatids with various of 100’s of genes/alleles 

Recombination in eukaryotes (swapping only the alleles) 

• Homologous chromosomes align with each other during PROPHASE 1 and exchange of sections of NON-SISTER CHROMATIDS occur by CROSSING-OVER

• Precise breakages of each strand 

• Equal exchange of CHROMATID material 

• Repair of breakage after GENETIC exchange 

• Genetic exchange can involve large sections of the homologous chromosomes creating new chromatids with various of 100’s of genes/alleles 

Meiosis 1: Reductional division

• During Metaphase 1, WHAT are aligned at the WHAT facing opposite poles 

• Genetic diversity in gametes is increased due to WHAT 

• The homologous chromosomes are separated during WHAT 

• Therefor, after meiosis 1, the chromosome number is WHAT, but there are HOW MANY chromatids/chromosomes 

• Unlike mitosis (and meiosis 2) the sister chromatids are not WHAT 

• The sister chromatids are no longer WHAT due to WHAT 

Meiosis 1: Reductional division

• During Metaphase 1, HOMOLOGOUS CHROMOSOMES are aligned at the EQUATOR facing opposite poles 

• Genetic diversity in gametes is increased due to INDEPENDENT ASSORTMENT 

• The homologous chromosomes are separated during ANAPHASE 1 

• Therefor, after meiosis 1, the chromosome number is HAPLOID, but there are TWO chromatids/chromosomes 

• Unlike mitosis (and meiosis 2) the sister chromatids are not SEPARATED 

• The sister chromatids are no longer IDENTICAL due to CROSSING OVER 

Meiosis 2

• No WHAT happens between meiosis 1 and meiosis 2 

• The process of meiosis 2 and mitosis is otherwise similar 

• Sister chromatids are separated during WHAT 

• At the end of meiosis 2, HOW MANY gametes are produced with a WHAT number of chromosomes (one chromatid/chromosome) that are not WHAT due to WHAT and WHAT 

Meiosis 2

• No DNA REPLICATION happens between meiosis 1 and meiosis 2 

• The process of meiosis 2 and mitosis is otherwise similar 

• Sister chromatids are separated during ANAPHASE 2 

• At the end of meiosis 2, 4 gametes are produced with a HAPLOID number of chromosomes (one chromatid/chromosome) that are not IDENTICAL due to CROSSING OVER and RANDOM ASSORTMENT