1. DNA and Molecular Genetics Chapter 3

2. Introduction Until now we have talked about genes simply as a functional part of the chromosome Need to consider how genes actually work in the cell (called expression of a gene) To understand how genes express, need to understand both their chemical composition and biochemical function

3. DNA and RNA Structure and Function Review: –DNA found mostly in chromosomes in nucleus –When cell is undergoing mitosis, chromosomes are short and thick –Rest of the time, chromosomes (and DNA) are long and thin [>5 ft in each cell!) –DNA exists in the form of a double-stranded helix –Helix – spiral staircase or twisted ladder shaped- structure –Double strand structure allows “easy” replication (making more) of the long, complicated DNA

4. Fig. 03-01 Fig. 03-01 DNA structure and location

5. DNA Structure and Replication DNA stands for deoxyribonucleic acid All nucleic acids formed by bonding together of nucleotides (type of molecule) Nuleotides – formed by bonding of three smaller molecules 1. Phosphate 2. Sugar (= deoxyribose molecule) 3. Nitrogen-containing base Note a base can “take up” (soak up) protons (positively charged particles = H+) Acids “give off” protons (H + ) When phosphate and N-containing base bond together  give off (H+) protons = the acid in DNA

6. DNA Structure and Function (con’t) Nucleotides Four nucleotides that make up DNA are 1.Adenine (A) 2.Thymine (T) 3.Cytosine (C) 4.Guanine (G) Nucleotides are joined together in a specific way, with phosphates forming the backbone of the DNA strand and bases projecting to the side Fig. 03-02

7. DNA Structure and Function (con’t) Double strands and base pairing DNA has two strands of nucleotides; this makes DNA a double helix Weak hydrogen bonds between the bases hold the strands together Different #’s of bonds causes only certain bases to bond together (called complementary base pairing) Complementary base pairing –Adenine (A) with thymine (T) –Guanine (G) with cytosine (C) –Could be vice-versa (T-A, C-G) Fig. 03-03

8. Replication of DNA Occurs as part of chromosome duplication Requires four steps 1.H-bonds between two strands of DNA break as enzymes unwind and “unzip” the DNA molecule 2.New nucleotides (always present in the nucleus) fit into place beside each old (parental) strand by complementary base pairing 3.New nucleotides become joined by enzyme called DNA polymerase (forms DNA polymer (molecule) 4.End up with two complete DNA molecules, identical to each other and to the original molecule Each new DNA is partly old (parental strand) and partly new (daughter strand)

9. Gene Expression Gene expression is the making of specific proteins (in ribosomes in cytoplasm and on rough ER) from specific nucleotide sequences (in DNA of genes in nucleus) Need a way to get information from nucleus to ribosomes  done with RNA Actually three types of RNA that all help to read the DNA code and produce proteins

10. Structure of RNA RNA (ribonucleic acid) made up of nucleotides containing the sugar ribose Four nucleotides making up RNA have 3 of the same bases as DNA (A,C,G) and one different, uracil (U) instead of thymine (T) RNA is single-stranded Fig. 03-05 Structure of RNA

11. Types of RNA Messenger RNA (mRNA) – carries genetic information from DNA to ribosomes where protein synthesis occurs Ribosomal RNA (rRNA) – combines with certain proteins to form ribosomes Transfer RNA (tRNA) – transfers amino acids “floating around” in cytoplasm, brings them to ribosomes in certain order specified by mRNA, bonds them together to form proteins Note: all types produced in nucleus by DNA according to DNA nucleotide sequence in specific gene

12. Structure and Function of Proteins Made up of subunits called amino acids (20 different AA’s) Specific sequence of amino acids dictates specific protein A (shortened) protein Another (shortened) protein Proteins can be structural (muscles) or enzymes = catalyze (speed up) chemical reactions

13. Structure and Function of Proteins (con’t) Reactions in cells form metabolic (chemical) pathways E A E B E C E D A  B  C  D  E Letters represent molecules, notations over arrows are enzymes. For example E A catalyzes reaction converting chemical A to chemical B, E B catalyzes catalyzes B to C, etc By DNA producing certain enzymes, can “turn on” certain chemical pathways in cell as needed  can form and maintain entire organism!

14. Back to Gene Expression Requires two steps –Transcription – making mRNA from specific portion of DNA (gene) –Translation – mRNA goes out into cytoplasm to ribosome, directs tRNAs to bring certain amino acids to ribosome, rRNA joins them together in certain sequence = a specific protein!

15. Transcription Occurs in nucleus Nucleotides in DNA are complementarily matched to form mRNA, substituting U for T mRNA then goes out of nucleus to ribosome for translation

16. Translation Occurs in cytoplasm Synthesis of polypeptide (many amino acids bonded together) under direction of mRNA mRNA tells rRNA which amino acid to go get from cytoplasm rRNA and protein in ribosome binds amino acids together in sequence directed by mRNA

17. Overview of Transcription and Translation Transcription Translation

18. Genetic Mutations Defined as a permanent change in the sequence of nucleotides in DNA Effect on protein activity (construction and/or function) may range from no effect to complete inactivity

19. Effect of Mutations Some genetic disorders already talked about in class are due to mutations Example: Phenylketonuria due to defect in gene expression for E A below; Albinism due to defect in gene expression for E B below Other genetic disorders due to gene defects include hemophilia B, Cystic fibrosis, and androgen insensitivity

20. Androgen Insensitivity Androgens are hormones needed by males (e.g. testosterone) to show secondary sex characteristics (broad shoulders, extra body hair, deeper voice, etc) In androgen insensitivity, a mutated gene prevents proper formation of androgen receptors on cells Results in cells not responding to androgens at puberty --> individual will instead develop some female secondary sexual characteristics (breasts, wider hips, etc.) A problem is realized when the person does not start to menstruate and seeks medical assistance  both X and Y chromosomes found in cells and person found lacking in internal sexual organs of a female. A genetic male with androgen insensitivity