Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Altering the Genetic Message Chapter 18 Copyright © McGraw-Hill Companies Permission required for reproduction or display

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Outline Mutations Changes in Gene Position Cancer Recombination Gene Transfer Reciprocal Recombination Trinucleotide Repeats Eukaryotic DNA

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Mutations are Rare But Important Although organisms have evolved many mechanisms to avoid errors during DNA replication, mutations do occur.  If changes were common, genetic instructions would soon degrade. All evolution begins with alterations in the genetic message.  Rate of evolution is ultimately limited by the rate alternative combinations are produced.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Kinds of Mutation Only mutations in the germ line (cells that form gametes) are passed to subsequent generations.  Mutations in somatic cells may have large effect on the individual, as they are passed on to other cells in the same individual.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Kinds of Mutation Point Mutations  Alterations involving one or a few base pairs. - Spontaneous pairing errors during replication. - Mutagens. Transposition  Individual genes may move within the genome. - Chromosomal Rearrangement

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Point Mutations Physical Damage to DNA  Ionizing Radiation - Highly mutagenic. Produce free radicles that cause a double-strand break.  Can not be fixed by cell’s usual mutational repair enzymes.  Ultraviolet Radiation - Strongly absorbed in pyrimidine bases.  May form pyrimidine dimer.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Pyrimidine Dimer Copyright © McGraw-Hill Companies Permission required for reproduction or display

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Point Mutations Chemical Modification of DNA  Three Chemical Classes - Chemicals that repair DNA, but pair incorrectly. - Chemicals that remove the amino group from adenine or cytosine. - Chemicals that add hydrocarbon groups to nucleotide bases.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Point Mutations Chemical Modification of DNA  Spontaneous Mutations - Slipped mispairings are caused when sequences misalign causing a portion of one strand to loop out.  Transitory - quickly repaired.  If not reverted before the cell corrects it, the segments will be excised out, causing a deletion.  Frame-Shift Mutation

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Changes in Gene Position Chromosomal Rearrangement  Translocations - Segments of one chromosome become part of another chromosome.  Inversions - Orientation of a portion of chromosome is reversed.  Aneuploidy - Genes or chromosome segments are added or deleted.  Polyploidy - Entire sets of chromosomes added.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Inversion Copyright © McGraw-Hill Companies Permission required for reproduction or display

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Changes in Gene Position Insertional Inactivation  Transposons are capable of moving to different locations in the genome. - Select new locations at random.  May cause insertional inactivation.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Cancer Cancer is a growth disorder of cells.  Uncontrolled and invasive growth. - Results in tumor.  May metastasize.  Can be caused by mutagenic chemicals or possibly viruses. - Cell division never stops in a cancerous line, and are thus essentially immortal.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Kinds of Cancer Sarcomas - Arise in connective tissue or muscle. Carcinomas - Arise in epithelial tissue.  Carcinogens are agents thought to cause cancer. - Ames Test  Carcinogenic chemicals are all mutagenic.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Tumors From Viral Infection Rous avian sarcoma virus (RSV) has been associated with chicken sarcomas.  Retrovirus - Cancer results from inappropriate activity of growth-promoting genes that are less active or completely inactive in normal cells.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Cancer and the Cell Cycle Transfection - Nuclear DNA from tumor cells is isolated and cleaved into random fragments, and tested for ability to induce cancer. Single nucleotide substitutions (Point mutations) have been shown to lead to cancer.  Cells inhibition of telomerase in somatic cells is a natural brake on cancer. - Inactivation of inhibition may help induce cancer.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Cancer and the Cell Cycle Proto-oncogenes are genes encoding proteins that stimulate cell division.  Mutated proto-oncogenes become cancer- causing genes (oncogenes). - Mutated alleles of many oncogenes are genetically dominant.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Cancer and the Cell Cycle In healthy cells, cell division is normally turned off by proteins encoding for tumor suppressor genes.  Almost half of all cancers involve mutations of the p53 gene.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Cancer and the Cell Cycle Cells control proliferation at several checkpoints.  All these controls must be inactivated for cancer to be initiated. - Induction of most cancers involves mutations of several genes.  Explains why most cancers occur in people over 40.  More time for individual cells to accumulate multiple mutations.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Smoking and Cancer About one-third of all cancer cases in the United States are directly attributable to cigarette smoking.  Smoke contains many mutagenic chemicals, and places them in direct contact with lung tissues. - Damages genes of epithelial cells lining the lungs.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Curing Cancer Preventing Start of Cancer  Receiving Signal to Divide - Mutations that increase number of receptors on cell surface amplify the division signal.  Relay Switch - Passage of signal into the cell’s interior.  Relay switch stuck in “ON” position.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Curing Cancer  Amplifying the Signal - Amplification of signal within cytoplasm.  Releasing the Brake - Used to restrain cell division.  Checking Readiness - Ensures DNA is undamaged and ready to divide.  Stepping on the Gas - Restore telomerase inhibitor.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Curing Cancer Preventing the Spread of Cancer  Tumor Growth - Angiogenesis Inhibitors  Metastasis - Cells break off and migrate.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Overview of Recombination Genetic Recombination represents an alteration in the genomic location of a gene, or a gene fragment. Gene Transfer - One chromosome or genome donates a segment to another chromosome or genome. Reciprocal Recombination - Two chromosomes trade segments.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Gene Transfer Plasmid Creation  All cells have recombination enzymes that can cause double duplexes to undergo reciprocal exchange. - Loop is freed from rest of DNA and becomes a plasmid. Integration  Region of plasmid DNA involved in original exchange, recognition site, aligns with matching sequence on main genome.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Gene Transfer Conjugation  Bacteria have genes encoding protein subunits that assemble on the surface of the bacterial cell, forming a pilus. - Rolling Circle Replication

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Gene Transfer Between Bacteria Copyright © McGraw-Hill Companies Permission required for reproduction or display

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Gene Transfer Transposition  Transposons encode transposase enzyme that inserts transposon into genome at a random site. - Causes insertional inactivation. - Facilitates gene mobilization.  Transposition can rapidly generate composite plasmids (resistance transfer factors). - Antibiotic Resistance

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

Reciprocal Recombination Crossing Over  Exchange between non-sister chromatids. Unequal Crossing Over  Crossover between regions similar, but not homologous, in nucleotide sequence. Gene Conversion  Alteration of one homologue by cell’s error detection and repair system.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Trinucleotide Repeats Trinucleotide repeat is a change in the genetic material producing an increase in the number of copies of repeated trinucleotide sequences.  Root cause of large number of inherited human disorders.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Classes of Eukaryotic DNA DNA That Codes for Protein  Four Classes: (1% of Human Genome) - Single-Copy Genes - Segmental Duplications - Multigene Families - Tandem Clusters

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Classes of Eukaryotic DNA Noncoding DNA  Introns (Noncoding DNA with Genes) - 24% of Human Genome  Structural DNA - 20% of Human Genome  Repeated Sequences - 3% of Human Genome  Transposable Elements - 45% of Human Genome

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Review Mutations Changes in Gene Position Cancer Recombination Gene Transfer Reciprocal Recombination Trinucleotide Repeats Eukaryotic DNA

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies Copyright © McGraw-Hill Companies Permission required for reproduction or display