1. Copyright © 2009 Pearson Education, Inc. Chapter 13 & 14 Essentials of Genetics Relationship between Gene Mutations, Amino Acid Side Chains, and Protein Structure

2. Copyright © 2009 Pearson Education, Inc. 13.8: Chemical Nature of R-Groups Each Side Chain has a characteristic chemical behavior. This behavior will determine the Secondary and Tertiary structure of a folded protein.

3. Copyright © 2009 Pearson Education, Inc. Predictable Behavior of Side Chains Hydrophobic – R-groups will force the protein to fold and allow this side chain to be away from water. Hydrophilic – R-groups want to be toward water. Acids – R-groups will form ionic bonds with R- groups that are Bases. The 3-D structure is a PRODUCT of the primary order of amino acids.

4. Copyright © 2009 Pearson Education, Inc. Protein Structure, a Reminder… Primary – straight chain of amino acids held together by peptide bonds. Secondary – alpha helix or beta- pleated sheet held together by hydrogen bonds. Tertiary – globular structure; 3- dimensional shape determined by side chain chemistry of individual amino acids. Quarternary – more than one tertiary structures that fit together in a complimentary way.

5. Copyright © 2009 Pearson Education, Inc. How Does a Polypeptide Become a Protein? Folding occurs in the watery cytosol HydroPHOBIC amino acids want to be Near other hydrophobic amino acids Away from the watery cytosol/in the interior of the folded structure. HydroPHILIC amino acids are located along the surface/outer edge Disulfide bonds form between cysteine molecules. Acids and bases form ionic bonds.

6. Copyright © 2009 Pearson Education, Inc. The Role of Chaperones Chaperones are proteins that assist in the folding of other proteins. Mediate the process of folding my preventing the formation of incorrect patterns. They do not become a part of the final product although they do bind to the polypeptide as it is folding. If the correct structure is NOT made UBIQUITINS tag them for destruction by proteasomes.

7. Copyright © 2009 Pearson Education, Inc. Impact of Mis-folding Mis-folded proteins can be nonfunctional Sickle Cell Anemia EB OI Cystic fibrosis Mis-folded proteins can accumulate and cause cell destruction. Prion Diseases Huntington Disease Alzheimer Disease Parkinson Disease

8. Copyright © 2009 Pearson Education, Inc. 13.9: Proteins Have Diverse Roles Proteins are the essence of cellular function. Most abundant organic macromolecule in cells. Structural/Fibrous proteins like collagen and keratin Contractile proteins like actin and myosin Functional/Globular proteins like hemoglobin, myoglobin, and immunoglobulins Largest functional group - Enzymes – biological catalysts that require a specifically shaped ACTIVE SITE for normal function.

9. Copyright © 2009 Pearson Education, Inc. 14.1Mutations Are Classified in Various Ways Mutation is any base pair change. Can involve a single base pair substitution, deletion or insertion of one or more bases, or major alterations in chromosome structure. How they occur: Spontaneous or Induced? Where have they occurred/location? Somatic Germline Autosomal X-linked

10. Copyright © 2009 Pearson Education, Inc. 14.1Spontaneous or Induced Spontaneous mutations appear to have no known cause. No known agents are associated with this occurrence. Assumed to be accidental. Induced mutations are due to an extraneous factor that may be natural or artificial. Examples include radiation and both natural and man-made chemicals. We call these MUTAGENS

11. Copyright © 2009 Pearson Education, Inc. 14.1Location Somatic occur in any cell except gametes Mutations DO NOT pass on to offspring Germline occur in gametes Mutations DO pass on to offspring Autosomal occur on autosomes X-linked occur on X chromosomes Express differently in males and females due to presence of 1 or 2 X chromosomes. Description of mutation can be combination of above terms: Autosomal somatic Autosomal germline X-linked somatic X-linked germline

12. Copyright © 2009 Pearson Education, Inc. Classification Based on Type of Molecular Change If the triplet code does not

13. Copyright © 2009 Pearson Education, Inc. Point Mutation Change in ONE nucleotide of a triplet Occurs in protein-coding (exon) portion Creates NEW triplet code Same amino acid = silent mutation (degeneracy) Different amino acid = missense mutation Same side chain group has less impact than different side chain group. Results in STOP codon = nonsense mutation Frameshift Mutation Alters reading frame, changes every amino acid following insertion or deletion.

14. Copyright © 2009 Pearson Education, Inc. What is their Phenotype effect? Loss-of-function Gain-of-function Morphological Nutritional Behavioral Lethal Conditional

15. Copyright © 2009 Pearson Education, Inc. Loss-of-function – reduces or eliminates function of gene. Null mutation – complete loss of function. Gain-of-function – enhanced or new function. Morphological – visible alterations of phenotype. Nutritional – loss of ability to synthesize an amino acid or vitamin. Behavioral – difficult to analyze; defect that changes mating behaviors, etc. Lethal – interrupts process essential to survival. Conditional – expression depends on environment.