A&P Ch4 PDF

Chapter 4 Genes and Cellular Function ANATOMY & PHYSIOLOGY The Unity of Form and Function Ninth Edition Kenneth S. Saladin © 2022 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permit...

Chapter 4 Genes and Cellular Function ANATOMY & PHYSIOLOGY The Unity of Form and Function Ninth Edition Kenneth S. Saladin © 2022 McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.  Introduction Necessary to have some familiarity with DNA and genes in order to study genetic disorders that effect hereditary traits Color blindness, cystic fibrosis, diabetes mellitus, hemophilia Mendelian genetics helps us discern and predict patterns of inheritance within a family line © McGraw Hill 2  4.1 DNA and RNA—The Nucleic Acids Expected Learning Outcomes: Describe the structure of DNA and relate this to its function. Explain how DNA and proteins are organized to form the chromosomes. Describe the types of RNA, their structural and functional differences, and how they compare with DNA. © McGraw Hill 3  DNA and RNA—The Nucleic Acids Johann Friedrich Miescher (1844 to 95) Swiss biochemist, studied the nuclei of white blood cells from pus extracted from bandages Coined term nuclein, now called deoxyribonucleic acid (DNA), repository for genes By 1900, components of DNA were known (sugar, phosphate groups, nitrogenous bases) In 1953, the overall structure of DNA was learned © McGraw Hill 4  DNA Structure and Function 1 Deoxyribonucleic acid (DNA) Long, thread-like molecule with uniform diameter, but varied length 46 DNA molecules (chromosomes) in nucleus of most human cells Average human DNA molecule about 2 in. long DNA and other nucleic acids are polymers of nucleotides A nucleotide consists of a sugar, phosphate group, and nitrogenous base © McGraw Hill 5  DNA Structure and Function 2 A single nucleotide consists of: One sugar—deoxyribose One phosphate group One nitrogenous base DNA bases: A, T, C, G Purines—double ring Adenine (A) Guanine (G) Pyrimidines—single ring Cytosine (C) Thymine (T) Figure 4.1a Access the text alternative for slide images. Uracil (U) © McGraw Hill 6  Nitrogenous Bases Figure 4.1b © McGraw Hill 8  DNA Structure and Function 3 Double helix shape of DNA (resembles spiral staircase) Each sidepiece is a backbone of phosphate groups alternating with deoxyribose Step-like connections between the backbones are pairs of nitrogen bases Access the text alternative for slide images. Figure 4.2 © McGraw Hill 9  DNA Structure and Function 4 Nitrogenous bases united by hydrogen bonds DNA base pairing A purine on one strand always bound to a pyrimidine on the other A–T C–G A–T two hydrogen bonds C–G three hydrogen bonds Law of complementary base pairing The base sequence on one strand of DNA determines the base sequence of the other © McGraw Hill 11  DNA Structure and Function 5 Gene Segment of DNA coding for the synthesis of a specific protein Genome All the genes of one person Humans have about 20,000 genes Only about 2% of total DNA Other 98% is noncoding DNA Plays role in chromosome structure Regulates gene activity © McGraw Hill 12  Discovery of the Double Helix 1900: components of DNA were known Sugar, phosphate, and bases 1953: X-ray diffraction revealed geometry of DNA molecule 1962: Nobel Prize for Physiology or Medicine awarded to James Watson, Francis Crick, and Maurice Wilkins Nobel prizes are only awarded to the living. Rosalind Franklin, whose X-ray data provided the final key to the double helix, died of cancer in 1959 at the age of 37 © McGraw Hill 13  RNA Structure and Function Ribonucleic acids (RNAs) Contain the sugar ribose Uracil (in RNA) replaces thymine (in DNA) Single nucleotide chain (not a double helix) Smaller than DNA, can have less than 100 or just over 10,000 bases per molecule Functions mainly in cytoplasm Three RNAs are important for protein synthesis Messenger RNA (mRNA) Ribosomal RNA (rRNA) Transfer RNA (tRNA) © McGraw Hill 20  4.2 Genes and Their Action Expected Learning Outcomes: Give a working definition of the gene and explain why new discoveries in genetics have changed our concept of what a gene is. Explain what the human genome is and what relationship it has to the health sciences. Define genetic code and describe how DNA codes for protein structure. Describe the process of assembling of amino acids to form a protein. Explain what happens to a protein after its amino acid sequence has been synthesized. Describe some ways that a gene can be turned on or off. Explain how DNA indirectly regulates the synthesis of nonprotein molecules. © McGraw Hill 21  What Is a Gene? 1 Previous definition: gene—a segment of DNA that carries the code for a particular protein But body has millions of proteins and only about 20,000 genes Current definition: gene—an information-containing segment of DNA that codes for the production of a molecule of RNA that plays a role in synthesizing one or more proteins Amino acid sequence of a protein is determined by the nucleotide sequence in the DNA © McGraw Hill 22  What Is a Gene? 2 46 human chromosomes come in two sets of 23 chromosomes One set of 23 chromosomes came from each parent Genome All the DNA in one 23-chromosome set 3.1 billion nucleotide pairs in human genome Genomics Study of the whole genome. How genes and noncoding DNA interact to affect structure and function of the organism © McGraw Hill 23  What Is a Gene? 4 Genomic Medicine Application of knowledge of the genome to the prediction, diagnosis, and treatment of disease Relevant to many disorders (for example, cancer, Alzheimer disease, schizophrenia, obesity, AIDS, tuberculosis) Currently we know locations of over 1,400 disease- producing mutations Allows for early detection of diseases, more effective clinical intervention Expands potential for gene-substitution therapy © McGraw Hill 25  The Genetic Code 1 Nucleotides code for amino acid sequences of proteins Body can make millions of different proteins (the proteome), from just 20 amino acids, and encoded by genes made of just four nucleotides (A, T, C, G) Minimum code to symbolize 20 amino acids is three nucleotides per amino acid © McGraw Hill 26  The Genetic Code 2 Base triplet Sequence of three DNA nucleotides that stands for one amino acid Codon 3-base sequence in mRNA 64 possible codons available to represent 20 amino acids 61 code for amino acids; 3 are stop codons Start codon—AUG codes for methionine, and begins the amino acid sequence of the protein Stop codons—UAG, UGA, and UAA: signal “end of message,” like a period at the end of a sentence © McGraw Hill 27  Protein Synthesis 1 All body cells, except sex cells and some immune cells, contain identical genes Different genes are activated in different cells Any given cell uses one-third to two-thirds of its genes Rest remain dormant and may be functional in other types of cells © McGraw Hill 28  Protein Synthesis 2 Process of protein synthesis DNA to mRNA to protein Transcription: DNA  mRNA Occurs within nucleus mRNA sequence complementary to gene Translation mRNA  protein mRNA migrates from the nucleus to cytoplasm where it codes for amino acids © McGraw Hill 29  Transcription 1 Transcription Copying genetic instructions from DNA to mRNA Certain DNA base sequences function as signal start RNA polymerase Binds to DNA and opens up the helix Reads bases from one strand of DNA to build a complementary strand of mRNA Where it finds C on the DNA, it adds G to the mRNA Where it finds G on the DNA, it adds C to the mRNA Where it finds T on the DNA, it adds A to the mRNA But where it finds A on the DNA, it adds U to the mRNA © McGraw Hill 30  Transcription 3 RNA initially produced is “immature” Introns are removed from RNA and exons spliced together Alternative splicing Variations in the way exons are spliced allow for a variety of proteins to be produced from one gene One gene can code for more than one protein Exons can be spliced together into a variety of different mRNAs © McGraw Hill 32  Alternative Splicing of mRNA Figure 4.6 Access the text alternative for slide images. © McGraw Hill 33  Translation 1 Nucleotide language converted into amino acid language Three main participants in translation: Messenger RNA (mRNA) Carries code from nucleus to cytoplasm Has protein cap that is recognition site for ribosome Transfer RNA (tRNA) Delivers a single amino acid to the ribosome Contains an anticodon—series of 3 nucleotides that are complementary to the mRNA codon Ribosomes. Organelles that read the message and build a peptide chain Free in cytosol, on rough ER, and on nuclear envelope © McGraw Hill 34  Translation of mRNA (1–2) Figure 4.8 (top) Access the text alternative for slide images. © McGraw Hill 42  Translation of mRNA (3–4) Figure 4.8 (bottom) © McGraw Hill 43  Translation 7 After translation, some proteins are packaged and some are exported Proteins headed for lysosomes or for secretion are made on ribosomes on the rough ER Newly made protein is threaded into rough ER where it is modified and packaged into a transport vesicle © McGraw Hill 44  Relationship of a DNA Base Sequence to Peptide Structure (a) DNA double helix. (b) Seven base triplets on the template strand of DNA. (c) The corresponding codons of mRNA transcribed from the DNA triplets. (d) The anticodons of tRNA that bind to the mRNA codons. (e) The amino acids carried by those six tRNA molecules. (f) The amino acids linked into a peptide chain. Figure 4.9 Access the text alternative for slide images. © McGraw Hill 45  Protein Processing and Secretion 2 Figure 4.10 Access the text alternative for slide images. © McGraw Hill 47  Gene Regulation 1 Genes can be turned on and off Cells can turn some genes permanently off Example: liver cells turn off hemoglobin genes Cells can turn genes on only when needed The level of gene expression can vary from day to day or hour to hour This can be controlled by chemical messengers such as hormones Example: Mammary gland cells turn on gene for casein protein only when breast milk is produced © McGraw Hill 52  Synthesizing Compounds Other Than Proteins Cells synthesize glycogen, fat, steroids, phospholipids, pigments, and other compounds No genes for these products, but their synthesis is under indirect genetic control They are produced by enzymatic reactions, and enzymes are proteins encoded by genes Example: production of testosterone (a steroid) A cell of the testes takes in cholesterol Enzymatically converts it to testosterone Only occurs when genes for enzyme are active Genes may greatly affect such complex outcomes as behavior, aggression, and sex drive © McGraw Hill 55  4.3 DNA Replication and the Cell Cycle 1 Expected Learning Outcomes: Describe how DNA is replicated. Discuss the consequences of replication errors. Describe the life history of a cell, including the events of mitosis. Explain how the timing of cell division is regulated. © McGraw Hill 56  4.3 DNA Replication and the Cell Cycle 2 Before a cell divides, it must duplicate its DNA so it can give a complete copy of all its genes to each daughter cell Since DNA controls all cellular function, this replication process must be very exact Law of complementary base pairing—we can predict the base sequence of one DNA strand if we know the sequence of the other © McGraw Hill 57  DNA Replication 1 Four steps of DNA replication: Unwinding Unzipping Building new DNA strands Repackaging Step 1: DNA unwinds from histones Replication fork—the point of DNA opening Step 2: DNA helicase unzips a segment of the double helix exposing its nitrogenous bases © McGraw Hill 58  DNA Replication 2 Step 3: DNA polymerase builds new DNA strands Polymerase reads exposed bases and matches complementary free nucleotides Separate polymerase molecules work on each strand proceeding in opposite directions The polymerase moving toward the replication fork makes a long, continuous, new strand of DNA The polymerase moving away from the replication fork makes short segments of DNA; DNA ligase joins them together Ultimately, two daughter DNA molecules are made from the original parental DNA Semiconservative replication—each daughter DNA consists of one old and one new helix © McGraw Hill 59  DNA Replication 3 Step 4: Newly made DNA is repackaged With thousands of polymerase molecules working simultaneously on the DNA, all 46 chromosomes are replicated in 6 to 8 hr Millions of histones are made in the cytoplasm while DNA is replicated and they are transported into the nucleus soon after DNA replication ends Each new DNA helix wraps around the histones to make new nucleosomes © McGraw Hill 60  Semiconservative DNA Replication Figure 4.13 Access the text alternative for slide images. © McGraw Hill 61  Errors and Mutations DNA polymerase makes mistakes DNA Damage Response (DDR) Mechanisms in place to correct replication errors DNA polymerase double checks the new base pair and tends to replace incorrect, biochemically unstable pairs with more stable, correct pairs Result is only one error per 1 billion bases replicated Mutations Changes in DNA structure due to replication errors or environmental factors (radiation, viruses, chemicals) Some mutations cause no ill effects, others kill the cell, turn it cancerous, or cause genetic defects in future generations © McGraw Hill 62  The Cell Cycle 1 The cell cycle includes interphase and the mitotic phase Interphase includes three subphases: First gap phase (G1) Synthesis phase (S) Second gap phase (G2) Mitotic phase includes multiple subphases: Prophase Metaphase Anaphase Telophase Cytokinesis © McGraw Hill 63  The Cell Cycle 2 Figure 4.14 Access the text alternative for slide images. © McGraw Hill 64  The Cell Cycle 3 Interphase G1: first gap phase Interval between cell birth (from division) and DNA replication Cell carries out normal tasks and accumulates materials for next phase S: synthesis phase Cell replicates all nuclear DNA and duplicates centrioles G2: second gap phase Interval between DNA replication and cell division Cell repairs DNA replication errors, grows and synthesizes enzymes that control cell division © McGraw Hill 65  The Cell Cycle 4 Mitotic phase Cell replicates its nucleus Pinches in two to form new daughter cells G0 (G zero) phase describes cells that have left the cycle and cease dividing for a long time (or permanently) Cell cycle duration varies between cell types © McGraw Hill 66  Mitosis 1 Mitosis is cell division resulting in two genetically identical daughter cells Functions of mitosis Development of individual from fertilized egg to about 50 trillion cells Growth of all tissues and organs after birth Replacement of cells that die Repair of damaged tissues Four phases of mitosis Prophase Metaphase Anaphase Telophase © McGraw Hill 67  Mitosis 6 Cytokinesis Division of cytoplasm into two cells Telophase is the end of nuclear division but overlaps cytokinesis Achieved by myosin protein pulling on actin in the terminal web of cytoskeleton Creates cleavage furrow around the equator of cell Cell pinches in two © McGraw Hill 72