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Biology Copyright Pearson Prentice Hall 12–1 DNA Copyright Pearson Prentice Hall Bell Work 4-20-2015 1. What is the control center of a cell? 2. What are the 3 critical things genes were known to do by the early scientist? (p. 291) Learning Target I can explain how scientist discovered the relationship between genes and DNA. Learning Target I can explain how scientist discovered the relationship between genes and DNA. Agenda: 1. Bell Work / LT 2. Biologist Timeline ?????? What was Fredrick Griffith trying to learn? Why was he trying to learn how bacteria made people sick? Why is it important to learn how bacteria causes diseases? Griffith and Transformation Griffith and Transformation In 1928, British scientist Fredrick Griffith was trying to learn how certain types of bacteria caused pneumonia. He isolated two different strains of pneumonia bacteria from mice and grew them in his lab. Griffith and Transformation Griffith made two observations: (1) The disease-causing strain of bacteria grew into smooth colonies on culture plates. (2) The harmless strain grew into colonies with rough edges. Who can describe Griffiths first experiment? Griffith and Transformation Griffith's Experiments Griffith set up four individual experiments. Experiment 1: Mice were injected with the disease-causing strain of bacteria. The mice developed pneumonia and died. Second experiment? Griffith and Transformation Experiment 2: Mice were injected with the harmless strain of bacteria. These mice didn’t get sick. Harmless bacteria (rough colonies) Lives Third experiment? Copyright Pearson Prentice Hall Griffith and Transformation Experiment 3: Griffith heated the diseasecausing bacteria. He then injected the heat-killed bacteria into the mice. The mice survived. Heat-killed diseasecausing bacteria (smooth colonies) Lives Fourth experiment? Copyright Pearson Prentice Hall Griffith and Transformation Experiment 4: Griffith mixed his heat-killed, disease-causing bacteria with live, harmless bacteria and injected the mixture into the mice. The mice developed pneumonia and died. What did Griffith conclude? Griffith and Transformation Griffith concluded that the heatkilled bacteria passed their disease-causing ability to the harmless strain. Copyright Pearson Prentice Hall What did Griffith call this process of changing one molecule into another? Copyright Pearson Prentice Hall Griffith and Transformation Transformation Griffith called this process transformation because one strain of bacteria (the harmless strain) had changed permanently into another (the diseasecausing strain). Griffith hypothesized that a factor must contain information that could change harmless bacteria into disease-causing ones. Copyright Pearson Prentice Hall What did Avery want to determine? Copyright Pearson Prentice Hall Avery and DNA Avery and DNA Oswald Avery repeated Griffith’s work to determine which molecule was most important for transformation. Avery and his colleagues made an extract from the heat-killed bacteria that they treated with enzymes. Copyright Pearson Prentice Hall How did Avery go about this testing? Avery and DNA The enzymes destroyed proteins, lipids, carbohydrates, and other molecules, including the nucleic acid RNA. Transformation still occurred. What is the next step Avery took? Avery and DNA Avery and other scientists repeated the experiment using enzymes that would break down DNA. When DNA was destroyed, transformation did not occur. Therefore, they concluded that DNA was the transforming factor. What was Avery's conclusion? Copyright Pearson Prentice Hall Avery and DNA Avery and other scientists discovered that the nucleic acid DNA stores and transmits the genetic information from one generation of an organism to the next. What question did Hershey and Chase want answers to? The The Hershey-Chase Hershey-Chase Experiment Experiment Alfred Hershey and Martha Chase studied viruses—nonliving particles smaller than a cell that can infect living organisms. Copyright Pearson Prentice Hall The Hershey-Chase Experiment Wanted to know if genes were made of protein or DNA. Bacteriophages A virus that infects bacteria is known as a bacteriophage. Bacteriophages are composed of a DNA or RNA core and a protein coat. Copyright Pearson Prentice Hall How did they go about their experiment? The Hershey-Chase Experiment They grew viruses in cultures containing radioactive isotopes of phosphorus-32 (32P) and sulfur-35 (35S). The Hershey-Chase Experiment If 35S was found in the bacteria, it would mean that the viruses’ protein had been injected into the bacteria. Bacteriophage with suffur-35 in protein coat Phage infects bacterium No radioactivity inside bacterium The Hershey-Chase Experiment If 32P was found in the bacteria, then it was the DNA that had been injected. Bacteriophage with phosphorus-32 in DNA Phage infects bacterium Radioactivity inside bacterium What did they find in the bacteria? Copyright Pearson Prentice Hall The Hershey-Chase Experiment Nearly all the radioactivity in the bacteria was from phosphorus (32P). Hershey and Chase concluded that the genetic material of the bacteriophage was DNA, not protein. The Components and Structure of DNA The Components and Structure of DNA DNA is made up of nucleotides. A nucleotide is a monomer of nucleic acids made up of: Deoxyribose Phosphate – 5-carbon Sugar Group Nitrogenous Base The Components and Structure of DNA There are four kinds of bases in in DNA: adenine guanine cytosine thymine Copyright Pearson Prentice Hall The Components and Structure of DNA Chargaff's Rules Erwin Chargaff discovered that: The percentages of guanine [G] and cytosine [C] bases are almost equal in any sample of DNA. The percentages of adenine [A] and thymine [T] bases are almost equal in any sample of DNA. Copyright Pearson Prentice Hall The Components and Structure of DNA X-Ray Evidence Rosalind Franklin used X-ray diffraction to get information about the structure of DNA. She aimed an X-ray beam at concentrated DNA samples and recorded the scattering pattern of the Xrays on film. The Double Helix The Components and Structure of DNA Using clues from Franklin’s pattern, James Watson and Francis Crick built a model that explained how DNA carried information and could be copied. Watson and Crick's model of DNA was a double helix, in which two strands were wound around each other. The Components and Structure of DNA DNA Double Helix The Components and Structure of DNA Watson and Crick discovered that hydrogen bonds can form only between certain base pairs—adenine and thymine, and guanine and cytosine. This principle is called base pairing. Bell Work 4-21-2015 1. What does a double helix look like? 2. Use the scissors on your desk to cut out the pieces for a double helix. Learning Target. I can explain a double helix. Learning Target. I can explain a double helix. Agenda 1. Bell Work / LT 2. Plickers 3. Activity 4. Discussion Bell Work 1. 2. 3. 4-22-2015 What does a double helix look like? What is the pattern for base pairing? Name the molecules that make up the sides of the DNA Ladder. Learning Target I can explain the structure of a double helix. Learning Target I can explain the structure of a double helix. Agenda 1. Bell Work / LT 2. Review Assignment 3. Activity 4. Plickers Copyright Pearson Prentice Hall 12–1 Avery and other scientists discovered that DNA is found in a protein coat. DNA stores and transmits genetic information from one generation to the next. transformation does not affect bacteria. proteins transmit genetic information from one generation to the next. Copyright Pearson Prentice Hall 12–1 The Hershey-Chase experiment was based on the fact that DNA has both sulfur and phosphorus in its structure. protein has both sulfur and phosphorus in its structure. both DNA and protein have no phosphorus or sulfur in their structure. DNA has only phosphorus, while protein has only sulfur in its structure. Copyright Pearson Prentice Hall 12–1 DNA is a long molecule made of monomers called nucleotides. purines. pyrimidines. sugars. Copyright Pearson Prentice Hall 12–1 Chargaff's rules state that the number of guanine nucleotides must equal the number of cytosine nucleotides. adenine nucleotides. thymine nucleotides. thymine plus adenine nucleotides. Copyright Pearson Prentice Hall 12–1 In DNA, the following base pairs occur: A with C, and G with T. A with T, and C with G. A with G, and C with T. A with T, and C with T. Copyright Pearson Prentice Hall 12-2 Chromosomes and DNA Replication Copyright Pearson Prentice Hall Bell Work 4-21-2015 1. Considering your knowledge of DNA, what might happen if bases paired incorrectly? 2. What is the pattern for base pairing? 3. Name the molecules that make up the sides of the DNA Ladder. Learning Target I can explain DNA replication. Learning Target I can explain DNA replication. Agenda 1. Bell Work / LT 2. Discussion of RNA 3. Assignment 4. Quizlet Research Where is DNA found in both prokaryotic and eukaryotic cells? DNA and Chromosomes DNA and Chromosomes In prokaryotic cells, DNA is located in the cytoplasm. Most prokaryotes have a single DNA molecule containing nearly all of the cell’s genetic information. Copyright Pearson Prentice Hall DNA and Chromosomes Chromosome E. Coli Bacterium Bases on the Chromosomes Copyright Pearson Prentice Hall DNA and Chromosomes Many eukaryotes have 1000 times the amount of DNA as prokaryotes. Eukaryotic DNA is located in the cell nucleus inside chromosomes. number of chromosomes varies widely from one species to the next. Copyright Pearson Prentice Hall DNA and Chromosomes Chromosome Structure Eukaryotic chromosomes contain DNA and protein, tightly packed together to form chromatin. Chromatin consists of DNA tightly coiled around proteins called histones. DNA and histone molecules form nucleosomes. Nucleosomes fiber. Copyright Pearson Prentice Hall pack together, forming a thick DNA and Chromosomes Eukaryotic Chromosome Structure Chromosome Nucleosome DNA double helix Coils Supercoils Histones Copyright Pearson Prentice Hall Research What is DNA Replication? https://www.youtube.com/watch?v=27TxKoFU2Nw DNA Replication DNA Replication Each strand of the DNA double helix has all the information needed to reconstruct the other half by the mechanism of base pairing. In most prokaryotes, DNA replication begins at a single point and continues in two directions. Copyright Pearson Prentice Hall DNA Replication In eukaryotic chromosomes, DNA replication occurs at hundreds of places. Replication proceeds in both directions until each chromosome is completely copied. The sites where separation and replication occur are called replication forks. Copyright Pearson Prentice Hall DNA Replication Duplicating DNA Before a cell divides, it duplicates its DNA in a process called replication. Replication ensures that each resulting cell will have a complete set of DNA. Copyright Pearson Prentice Hall DNA Replication During DNA replication, the DNA molecule separates into two strands, then produces two new complementary strands following the rules of base pairing. Each strand of the double helix of DNA serves as a template for the new strand. Copyright Pearson Prentice Hall DNA Replication New Strand Original strand Nitrogen Bases Growth Growth Replication Fork Replication Fork DNA Polymerase Copyright Pearson Prentice Hall Research How does replication occur? Copyright Pearson Prentice Hall How Replication Occurs DNA replication is carried out by enzymes that “unzip” a molecule of DNA. Hydrogen bonds between base pairs are broken and the two strands of DNA unwind. Copyright Pearson Prentice Hall DNA Replication The principal enzyme involved in DNA replication is…. DNA polymerase joins individual nucleotides to produce a DNA molecule and then “proofreads” each new DNA strand. Copyright Pearson Prentice Hall 12– 2 In prokaryotic cells, DNA is found in the cytoplasm. nucleus. ribosome. cell membrane. Copyright Pearson Prentice Hall 12– 2 The first step in DNA replication is producing two new strands. separating the strands. producing DNA polymerase. correctly pairing bases. Copyright Pearson Prentice Hall 12– 2 A DNA molecule separates, and the sequence GCGAATTCG occurs in one strand. What is the base sequence on the other strand? GCGAATTCG CGCTTAAGC TATCCGGAT GATGGCCAG Copyright Pearson Prentice Hall 12– 2 In addition to carrying out the replication of DNA, the enzyme DNA polymerase also functions to unzip the DNA molecule. regulate the time copying occurs in the cell cycle. “proofread” the new copies to minimize the number of mistakes. wrap the new strands onto histone proteins. Copyright Pearson Prentice Hall 12– 2 The structure that may play a role in regulating how genes are “read” to make a protein is the coil. histone. nucleosome. chromatin. Copyright Pearson Prentice Hall 12–3 RNA and Protein Synthesis 12-3 RNA and Protein Synthesis Copyright Pearson Prentice Hall Bell Work 4-21-2015 1. What might you compare the looks of a supercoiled nucleosome to that you are familiar? 2. What is chromatin? 3. What is the job of a nucleosome? Learning Target I can explain the how RNA differs from DNA. Learning Target I can explain the how RNA differs from DNA. Agenda 1. Bell Work / LT 2. Discussion of RNA 3. Activity / Assignment 4. Plickers 5. Quizlet Research How does a gene Work? Copyright Pearson Prentice Hall 12–3 RNA and Protein Synthesis How does a gene Work? 1. Genes are coded DNA instructions that control the production of proteins. 2. Genetic messages can be decoded by copying part of the nucleotide sequence from DNA into RNA. 3. RNA contains coded information for making proteins. Copyright Pearson Prentice Hall Research What is the structure of RNA compare to DNA? Copyright Pearson Prentice Hall The Structure of RNA The Structure of RNA There are three main differences between RNA and DNA: The sugar in RNA is ribose instead of deoxyribose. RNA is generally single-stranded. RNA contains uracil in place of thymine. Copyright Pearson Prentice Hall Research What are the 3 types of RNA? Copyright Pearson Prentice Hall Types of RNA Types of RNA There are three main types of RNA: messenger ribosomal transfer RNA RNA RNA Copyright Pearson Prentice Hall Types of RNA Messenger RNA (mRNA) carries copies of instructions for assembling amino acids into proteins. ***Serve as “messengers” from DNA to the rest of the cell Copyright Pearson Prentice Hall Types of RNA Ribosomes are made up of proteins and ribosomal RNA (rRNA). Copyright Pearson Prentice Hall Types of RNA During protein construction, transfer RNA (tRNA) transfers each amino acid to the ribosome. Copyright Pearson Prentice Hall Research Describe Transcription. Copyright Pearson Prentice Hall Transcription DNA is copied in the form of a complementary sequence called RNA Requires RNA polymerase to bind to DNA and separate the DNA strands as a template to assemble the nucleotides into another DNA strand This first process is called transcription. The process begins at a section of DNA called a promoter, which has specific base sequence that signal Pearson Prentice Hall where Copyright to start Protein Synthesis DNA molecule DNA strand (template) 5 3 TRANSCRIPTION mRNA 5 3 Codon TRANSLATION Protein Amino acid Transcription RNA RNA polymerase DNA Copyright Pearson Prentice Hall Research What are the functions of introns and exons? Copyright Pearson Prentice Hall RNA Editing RNA Editing Some DNA within a gene is not needed to produce or code for a protein. These areas are called introns. The DNA sequences that code for proteins are called exons. Copyright Pearson Prentice Hall RNA Editing The introns are cut out of RNA molecules…scientist have no idea why… The exons are the spliced together to form mRNA. Copyright Pearson Prentice Hall Exon Intron DNA Pre-mRNA mRNA Cap Tail Bell Work 4-22-2015 1. Compare the DNA code to something you need a code to in your daily life. 2. What are the 3 types of RNA? 3. Explain transcription. Learning Target I can explain the genetic code. Learning Target I can explain the genetic code. Agenda 1. Bell Work / LT 2. Plickers 3. Discussion 4. Activity Research What is the genetic code? The Genetic Code The Genetic Code The genetic code is the “language” of mRNA instructions. The code is written using four “letters” (the bases: A, U, C, and G). Copyright Pearson Prentice Hall Research What is a codon? The Genetic Code A codon consists of three consecutive nucleotides on mRNA that specify a particular amino acid. Copyright Pearson Prentice Hall The Genetic Code There are 64 possible base codons… Copyright Pearson Prentice Hall Research What is translation and where does it take place? Translation Translation is the decoding of an mRNA message into a polypeptide chain (protein). Translation takes place on ribosomes. During translation, the cell uses information from messenger RNA to produce proteins and tell what order they should be listed in on the polypeptide. Nucleus Copyright Pearson Prentice Hall mRNA Translation The ribosome binds new tRNA molecules and amino acids as it moves along the mRNA. Phenylalanine Methionine Ribosome mRNA Start codon Copyright Pearson Prentice Hall tRNA Lysine Translation Lysine tRNA Protein Synthesis Translation direction mRNA Copyright Pearson Prentice Hall Ribosome Translation The process continues until the ribosome reaches a stop codon. Polypeptide Ribosome tRNA Copyright Pearson Prentice Hall mRNA Codon Genes and Proteins Codon Codon DNA Single strand of DNA mRNA Codon Codon Codon Protein mRNA Alanine Arginine Leucine Copyright Pearson Prentice Hall Amino acids within a polypeptide Bell Work 4-23-2015 1. Are enzymes tossed away or reused? 2. Log onto Quizlet and Study for Friday’s Vocabulary Formative. Learning Target I can explain DNA structure and Replication. Learning Target I can explain DNA structure and Replication. Agenda 1. Bell Work / LT 2. Quizlet 3. Activity 4. Plickers Bell Work 1. 4-24-2015 Log onto Quizlet and study for Formative. Learning Target I can earn a “3” on the review formative. Agenda 1. Bell Work / LT 2. Formative 3. Activity DNA Replication Enzyme Wrap Up Bell Work 1. 4-27-2015 Study for Formative. Learning Target I can earn a “3” on the Formative because I studied. Agenda 1. Bell Work / LT 2. Formative 3. Research Research 1. What are mutations? 2. Define: gene mutations, chromosomal mutations, polyploidy 3. Find and define the 2 Types of gene mutations. 4. Find examples of deletions, substitutions, translocations, insertions, inversions 5. How are genes regulated? 6. What are lac and hox genes? 7. How are lac genes turned off and on? 8. Define operon, operator, and differentiation. 9. How are eukaryotic genes regulated? 12– 3 The role of a master plan in a building is similar to the role of which molecule? messenger RNA DNA transfer RNA ribosomal RNA Copyright Pearson Prentice Hall 12– 3 A base that is present in RNA but NOT in DNA is thymine. uracil. cytosine. adenine. Copyright Pearson Prentice Hall 12– 3 The nucleic acid responsible for bringing individual amino acids to the ribosome is transfer RNA. DNA. messenger RNA. ribosomal RNA. Copyright Pearson Prentice Hall 12– 3 A region of a DNA molecule that indicates to an enzyme where to bind to make RNA is the intron. exon. promoter. codon. Copyright Pearson Prentice Hall 12– 3 A codon typically carries sufficient information to specify a(an) single base pair in RNA. single amino acid. entire protein. single base pair in DNA. Copyright Pearson Prentice Hall 12–4 Mutations Copyright Pearson Prentice Hall Bell work 4-28-2015 1. How can you study for the EOC? Refer to the EOC Cheat Sheet for #1-2: 2. Which of the following chemical formulas represent an organic molecule? A. H2O B. AgNO3 C. C12H22O11 3. Which of the following solutions has the greatest concentration of hydroxide ions? A. Urine (pH 6) B. Rainwater (pH 5.5) C. Gastric juice (pH 2.0) 4. What is translation and where does it take place? 5. What is transcription and where does it take place? Learning Target I can explain genetic mutations and how genes regulate themselves. Learning Target I can explain genetic mutations and how genes regulate themselves. Agenda 1. Bell Work 2. Discussion 3. Activity Research What are mutations? 12-4 Mutations Mutations are changes in the genetic material. Copyright Pearson Prentice Hall Kinds of Mutations Kinds of Mutations Gene mutations - Mutations that produce changes in a single gene Chromosomal mutations Mutations that produce changes in whole chromosomes Copyright Pearson Prentice Hall Kinds of Mutations Gene Mutations - involve a change in one or a few nucleotides - known as point mutations - they occur at a single point in the DNA sequence. Point mutations include substitutions, insertions, and deletions. Copyright Pearson Prentice Hall Kinds of Mutations Substitutions - usually affect no more than a single amino acid - a base is changed Copyright Pearson Prentice Hall Kinds of Mutations Frameshift mutations - The effects of insertions or deletions are more dramatic. - addition or deletion of a nucleotide causes a shift in the grouping of codons. Copyright Pearson Prentice Hall Kinds of Mutations In an insertion, an extra base is inserted into a base sequence. Copyright Pearson Prentice Hall Kinds of Mutations In a deletion, the loss of a single base is deleted and the reading frame is shifted. Copyright Pearson Prentice Hall Kinds of Mutations Chromosomal Mutations - involve changes in the number or structure of chromosomes. - include deletions, duplications, inversions, and translocations. Copyright Pearson Prentice Hall Kinds of Mutations Deletions involve the loss of all or part of a chromosome. Copyright Pearson Prentice Hall Kinds of Mutations Duplications produce extra copies of parts of a chromosome. Copyright Pearson Prentice Hall Kinds of Mutations Inversions reverse the direction of parts of chromosomes. Copyright Pearson Prentice Hall Kinds of Mutations Translocations occurs when part of one chromosome breaks off and attaches to another. Copyright Pearson Prentice Hall Significance of Mutations Significance of Mutations Many mutations have little or no effect on gene expression. Some mutations are the cause of genetic disorders. Polyploidy is the condition in which an organism has extra sets of chromosomes. Copyright Pearson Prentice Hall 12– 4 A mutation in which all or part of a chromosome is lost is called a(an) duplication. deletion. inversion. point mutation. Copyright Pearson Prentice Hall 12– 4 A mutation that affects every amino acid following an insertion or deletion is called a(an) frameshift mutation. point mutation. chromosomal mutation. inversion. Copyright Pearson Prentice Hall 12– 4 A mutation in which a segment of a chromosome is repeated is called a(an) deletion. inversion. duplication. point mutation. Copyright Pearson Prentice Hall 12– 4 The type of point mutation that usually affects only a single amino acid is called a deletion. a frameshift mutation. an insertion. a substitution. Copyright Pearson Prentice Hall 12– 4 When two different chromosomes exchange some of their material, the mutation is called a(an) inversion. deletion. substitution. translocation. Copyright Pearson Prentice Hall 12-5 Gene Regulation Gene Regulation: An Example Gene Regulation: An Example E. coli provides an example of how gene expression can be regulated. An operon is a group of genes that operate together. In E. coli, these genes must be turned on so the bacterium can use lactose as food. they are called the lac operon. Gene Regulation: An Example How are lac genes turned off and on? Gene Regulation: An Example lac genes are turned off by repressors turned on by the presence of lactose. Gene Regulation: An Example On one side of the operon's three genes are two regulatory regions. In the promoter (P) region, RNA polymerase binds and then begins transcription. Gene Regulation: An Example The other region is the operator (O). Gene Regulation: An Example When the lac repressor binds to the O region, transcription is not possible. Copyright Pearson Prentice Hall Gene Regulation: An Example When lactose is added, sugar binds to the repressor proteins. Copyright Pearson Prentice Hall Gene Regulation: An Example The repressor protein changes shape and falls off the operator and transcription is made possible. Copyright Pearson Prentice Hall Gene Regulation: An Example Many genes are regulated by repressor proteins. Some genes use proteins that speed transcription. Sometimes regulation occurs at the level of protein synthesis. Eukaryotic Gene Regulation How are most eukaryotic genes controlled? Eukaryotic Gene Regulation Eukaryotic Gene Regulation Operons are generally not found in eukaryotes. Most eukaryotic genes are controlled individually and have regulatory sequences that are much more complex than those of the lac operon. Eukaryotic Gene Regulation Many eukaryotic genes have a sequence called the TATA box. Direction of transcription Eukaryotic Gene Regulation The TATA box seems to help position RNA polymerase. Direction of transcription Eukaryotic Gene Regulation Eukaryotic promoters are usually found just before the TATA box, and consist of short DNA sequences. Direction of transcription Eukaryotic Gene Regulation Genes are regulated in a variety of ways by enhancer sequences. Many proteins can bind to different enhancer sequences. Some DNA-binding proteins enhance transcription by: opening up tightly packed chromatin helping to attract RNA polymerase blocking access to genes. Development and Differentiation Development and Differentiation As cells grow and divide, they undergo differentiation, meaning they become specialized in structure and function. Hox genes control the differentiation of cells and tissues in the embryo. Development and Differentiation Careful control of expression in hox genes is essential for normal development. All hox genes are descended from the genes of common ancestors. Development and Differentiation Hox Genes Fruit fly chromosome Mouse chromosomes Fruit fly embryo Mouse embryo Copyright Pearson Prentice Hall Adult fruit fly Adult mouse 12– 5 Which sequence shows the typical organization of a single gene site on a DNA strand? start codon, regulatory site, promoter, stop codon regulatory site, promoter, start codon, stop codon start codon, promoter, regulatory site, stop codon promoter, regulatory site, start codon, stop codon Copyright Pearson Prentice Hall 12– 5 A group of genes that operates together is a(an) promoter. operon. operator. intron. Copyright Pearson Prentice Hall 12– 5 Repressors function to turn genes off. produce lactose. turn genes on. slow cell division. Copyright Pearson Prentice Hall 12– 5 Which of the following is unique to the regulation of eukaryotic genes? promoter sequences TATA box different start codons regulatory proteins Copyright Pearson Prentice Hall 12– 5 Organs and tissues that develop in various parts of embryos are controlled by regulation sites. RNA polymerase. hox genes. DNA polymerase. Copyright Pearson Prentice Hall