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DNA and Its Role in Heredity Molecular Basis of Inheritance Chapter 9 Chapter 9 DNA and Its Role in Heredity Key Concepts 9.1 DNA Structure Reflects Its Role as the Genetic Material 9.2 DNA Replicates Semiconservatively 9.3 Mutations Are Heritable Changes in DNA Chapter 9 Opening Question What can we learn from ancient DNA? Search for Genetic Material Looking for a molecule that could be specific and show great variation Molecule needs to be abundant Needs to be able to be copied precisely What is your guess based on these requirements? Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material By the early 20th century, a “chromosomal theory of inheritance” had been developed, proposing that Mendel’s genes are on the chromosomes. Then evidence began to accumulate indicating that DNA is the genetic material. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Circumstantial evidence: – DNA is present in the cell nucleus and in chromosomes. – It doubles during S phase of the cell cycle. – There is twice as much in diploid cells as in haploid cells. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material DNA was first isolated in 1868 from white blood cell nuclei. The young Swiss researcher called the fibrous substance “nuclein,” and proposed that it was the genetic material. It was composed of C, H, O, N, and P. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Dyes were developed in the early 20th century that showed color when bound to DNA in dividing cells. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material The amount of dye that binds to DNA, and thus color intensity, is related to the amount of DNA present. The amount of DNA was analyzed in individual cells by passing them through a flow cytometer. Cells in G1 contained half the DNA that cells in S, G2, and M contained. All nondividing somatic cells have the same amount of DNA; gametes have half the amount. Figure 9.1 DNA in the Cell Cycle Figure 9.1 DNA in the Cell Cycle When dividing cells are stained and analyzed by flow cytometry, there are two populations in terms of DNA content, seen as two peaks in the above graph. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Chromosomes contain DNA, but also proteins, so scientists had to rule out proteins as the genetic material. In transformation experiments, it was shown that DNA from one strain of bacterium could genetically transform another strain: strain A + strain B DNA → bacterium strain B Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Viruses such as bacteriophage contain DNA and a little protein. Experiments showed that when a virus infects a bacterium, it injects only its DNA. Since the viral DNA genetically transforms the bacteria, this was further evidence for DNA as the genetic material. Evidence of Genetic Material Griffith looking for vaccine against Streptococcus pneumoniae 2 strains: S-smooth colonies; R-rough S are encapsulated with polysaccharide coat Alternative phenotypes (S and R) are inherited Griffith Experiment Injected live S strain into mice: mice died of pneumonia (S is pathogenic) Injected live R strain into mice: mice healthy (R is nonpathogenic) Mice injected with heat killed S: mice healthy Mice injected with heat killed S mixed w live R cells: mice died Blood samples from dead mice contained live S cells: R cell acquired from dead S cells ability to make coats TRANSFORMATION Transformation Implications Transformation: assimilation of external genetic material by a cell Not a protein-heat denatures proteins but heat did not destroy the transforming ability of the genetic material in the heat killed S cells Later Avery, McCarty, and MacLeod discovered transforming agent was DNA Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Egg cells can also be transformed in this way, resulting in a whole new genetically transformed organism— called transgenic. These methods form the basis of much applied research, including biotechnology and genetic engineering, and have provided strong evidence for DNA as the genetic material. Evidence of Viral DNA Bacteriophage (phage): virus that infects bacteria Alfred Hershey & Martha Chase DNA genetic material of phage T2 Virus was DNA and a protein coat Protein tagging: T2 and E. coli were grown DNA tagging: T2 and E. coli were grown in media w 32 P Phage structure Hershey and Chase Protein labeled infected E. coli DNA labeled infected separate E. coli Mixtures were agitated to break loose phage coats from bacteria Mixtures were centrifuged; cells in the pellet; viruses in the supernatant S labeled in supernatant P labeled in the pellet Bacteria P labeled released viruses w P Hershey and Chase’s Method Conclusions Hershey & Chase Viral proteins remain outside the host cell Viral DNA injected into host cell Injected DNA molecules cause cells to produce additional viruses w more viral DNA and proteins Nuclei acids not proteins are hereditary material Chargaff’s Experiment Analyzed DNA of different organisms DNA composition is species specific: amount and ratios of nitrogenous bases vary from one species to another Adenine residues equaled number of thymines; cytosines equaled number of guanines Chargaff’s rules A=T; G=C This molecular diversity supports DNA as hereditary material Concept 9.1 DNA Structure Reflects Its Role as the Material In 1950, ErwinGenetic Chargaff found the amount of A always equaled the amount of T, and amount of G always equaled the amount of C. Circumstantial Evidence for DNA Eukaryotic cell doubles DNA content prior to mitosis During mitosis, the doubled DNA is equally divided btwn 2 daughter cells Organism’s diploid cells have 2x DNA as haploid gametes Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material X-ray crystallography: positions of atoms in a crystallized substance can be inferred from the diffraction pattern of X rays passing through the substance Crystallographs of DNA were prepared in the early 1950s by Rosalind Franklin and suggested a spiral or helical molecule. Figure 9.4 X-Ray Crystallography Helped Reveal the Structure of DNA Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Chemical composition: Biochemists knew that nucleotides consisted of the sugar deoxyribose, a phosphate group, and nitrogencontaining bases: – Purines: adenine (A) and guanine (G) – Pyrimidines: cytosine (C) and thymine (T) Watson, Crick, & Franklin Working on 3D structure Wilkins fed Watson and Crick Franklin’s X ray of DNA crystal Watson and Crick deduced: Helix w uniform width of 2 nm Purine and pyrimidine bases stacked .34 nm apart Helix makes 1 full turn 3.4 nm There are 10 layers of bases in ea turn Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material 3-D model building: Francis Crick and James Watson combined all the knowledge of DNA to determine its structure. Franklin’s X-ray crystallography convinced them the molecule was helical. Density measurements suggested there are two polynucleotide chains in the molecule. Modeling showed that DNA strands must be antiparallel. Figure 9.5 DNA Is a Double Helix (Part 1) Figure 9.5 DNA Is a Double Helix (Part 2) Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Watson and Crick suggested that: • The bases are on the interior of the two strands, with a sugar-phosphate backbone on the outside. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material • Per Chargaff’s rule, a purine on one strand is paired with a pyrimidine on the other, making the base pairs (A–T and G–C) the same width down the helix. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material Four key features of DNA structure: – Double-stranded helix of uniform diameter The chains are held together by hydrogen bonds between the base pairs and by van der Waals forces between adjacent bases on the same strand. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material – The two strands are antiparallel. In the sugar–phosphate backbone, the phosphate groups are bonded to the 5ʹ carbon of one sugar and the 3ʹ carbon of the next. Figure 3.4 DNA Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material – The outer edges of the nitrogenous bases are exposed in major and minor grooves. The grooves exist because the helices are not evenly spaced. There are 4 possible configurations of the flat, hydrogen-bonded base pairs within the major and minor grooves. Figure 9.5 DNA Is a Double Helix (Part 2) Figure 9.6 Base Pairs in DNA Can Interact with Other Molecules (Part 1) Figure 9.6 Base Pairs in DNA Can Interact with Other Molecules (Part 2) Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material The surfaces of A–T and G–C base pairs are chemically distinct. Binding of proteins to specific base pair sequences is key to DNA–protein interactions, which are necessary for replication and gene expression. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material – The DNA double helix is right-handed. It can be found as a much less stable left-handed helix (Z-DNA or “zig-zag DNA”). It does not have grooves and is less compact. Forms in regions where DNA is being transcribed; it may help stabilize the DNA. Concept 9.1 DNA Structure Reflects Its Role as the Genetic Material DNA structure is essential to its functions: – Storage of genetic information – Precise replication during cell division by complementary base pairing – Susceptibility to mutations (stable changes in the genetic material) – Expression of the coded information as the phenotype DNA Structure Tried sugar phosphate chains on inside no go On outside, hydrophobic interactions of nitrogenous bases pushed them to inside Ladder twisted into a spiral 2 sugar phosphate backbones of the helix are antiparallel; they run in opposite directions One strand of DNA DNA rungs Pair of nitrogenous bases Purine must pair w pyrimidines to get .34 nm W Chargaff, A purine + T pyrimidine G purine + C pyrimidine Suggests mechanisms for DNA replication Sequences of bases highly variable allowing specificity for genetic coding Hydrogen bonds and van der waals stabilize DNA DNA Replication Watson & Crick proposed genes on original DNA strand are copied by specific pairing of complementary bases, creating a complementary strand Complementary strand can function as template to produce a copy of original strand 2 strands separate each acts as template for complementary strand Enzymes link nucleotides together at sugar-phosphate groups 3D models Meselson and Stahl 3 hypotheses Conservative: parental double helix remain intact and second DNA molecule entirely new molecule Semiconservative: each DNA molecules should be composed of one original & one new strand Dispersive: both strands of newly produced DNA molecules should contain mix of old and new DNA Meselson & Stahl Experiment Grew E coli on medium w 15N (heavy nitrogen) Transferred to medium w 14N 1st generation DNA extracted from E coli after on generation of growth in light medium 2nd generation DNA extracted from E coli after 2 replications in light medium Isolated DNA was mixed w CsCl & centrifuged Centrifugal force created CsCl gradient w >conc at bottom; DNA moved to place density matched density of CsCl Meselson & Stahl Method Results Meselson & Stahl Parents: 1 distinct band / tube 1st generation 1 distinct band near center 2nd generation 2 bands one near center other light Conclusions: Meselson & Stahl 1st generation all hybrid: semiconservative model 1st generation eliminated conservative, but not dispersive 2nd generation eliminated dispersive; only one band would have occurred if dispersive replication Semiconservative Replication DNA Replication Helical molecule must untwist (helicase) while it copies its two antiparallel strands simultaneously Requires 2 dozen enzymes and other proteins Prokaryotes: 500 nucleotides/sec Few hours to copy 6 billion bases of single human cell Accurate: 1 in a billion nucleotides is incorrectly paired Concept 9.2 DNA Replicates Semiconservatively Two general steps in DNA replication: – The double helix is unwound, making two template strands available for new base pairing. – Nucleotides form base pairs with template strands and are linked together by phosphodiester bonds. Figure 9.7 Each New DNA Strand Grows by the Addition of Nucleotides to Its 3ʹ End Concept 9.2 DNA Replicates Semiconservatively During DNA synthesis, new nucleotides are added to the 3′ end of the new strand, which has a free hydroxyl group (—OH). The DNA template is read 3ʹ to 5ʹ, and the new strand of DNA is generated 5ʹ to 3ʹ, forming an antiparallel double helix. Concept 9.2 DNA Replicates Semiconservatively DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) or deoxyribonucleotides. During synthesis, two of the phosphate groups are released, and the final nucleotide is a monophosphate (adenine, thymine, cytosine, or guanine). Release of the two outer phosphate groups provides energy for formation of a phosphodiester bond. Enzymes for Replication Origins of Replication DNA replication begins at sites called origins of replication that have a specific sequence of nucleotides Specific proteins required to initiate replication bind to origin DNA double helix opens at origin and replication forks spread in both directions away from point form replication bubble Prokaryotes one origin; eukaryotes thousands Concept 9.2 DNA Replicates Semiconservatively DNA polymerases are very large and shaped like an open right hand. The “palm” brings the active site and the substrates into contact. The “fingers” recognize the nucleotide bases. The enzyme then changes shape and catalyzes formation of a new phosphodiester bond. Figure 9.10 DNA Polymerase Binds to the Template Strand Elongating a new strand Helicases are enzymes which catalyze unwinding of parental double helix Single strand binding proteins keep strands apart and stabilize the unwound DNA until new strand can be synthesized DNA polymerases catalyze synthesis of a new DNA strand New nucleotides align on template of old DNA polymerase links nucleotides to growing strand; only grow from 5’ to 3’ only add to 3’ Concept 9.2 DNA Replicates Semiconservatively DNA polymerase works very fast but makes very few errors. It is processive—it catalyzes many sequential polymerization reactions each time it binds to DNA. A DNA polymerase can add thousands of nucleotides before it detaches from DNA. Replication is endergonic Requires energy Nucleoside triphosphate is source Covalently linked to 5’ carbon of pentose Nucleoside triphosphate lose 2 phosphates form covalent linkages to the growing chain Hydrolysis of phosphate bond drives synthesis of DNA Antiparallel Continuous synthesis of both DNA strands is not possible due to the antiparallel construction Can only elongate from 5’ to 3’ Continuous synthesis occurs on the leading strand which is 5’ to 3’ The lagging strand (complementary strand) has discontinuous synthesis Lagging strand produced as a number of short segments called Okazaki fragments Replication of antiparallel strands Okazaki Fragments Synthesized in 5’ to 3’ direction Fragments are 1000-2000 nucleotides in length in bacteria and 100-200 nucleotides long in eukaryotes Fragments are ligated by DNA ligase, linking enzyme that catalyzes formation of a covalent bond between the 3’ end of each new fragment and the 5’ end of the growing chain primer Primer is a short RNA segment that is complementary to DNA segment & that is necessary to begin DNA replication Primers are polymerized by an enzyme called primase Portion of parental DNA serves as template for primer w a base sequence that is about 10 nucleotides long in eukaryotes Primer formation must precede DNA replication, DNA polymerase only add nucleotides to a poly nucleotide that is already correctly base-paired w complementary strand primers Only one is needed for leading strand Thousands are needed for lagging strand RNA primer must initiate the synthesis of each Okazaki fragment Fragments are ligated in 2 steps to produce a continuous DNA strand DNA polymerase removes the RNA primer and replaces it w DNA; DNA ligase catalyzes linkage Between 3’ end of each fragment & 5’ of chain Enzymes repair damage Initial pairing errors occur at a frequency of 1 in 10K DNA can be repaired as it is being synthesized: mismatch repair DNA polymerase proofreads each newly added nucleotide against its template; if incorrect removes and replaces it (eukaryotes have proteins too to proofread) Excision repair: accidental changes in DNA can result from exposure; 50 different DNA repair enzymes; one excises and gap filled by base-pairing by DNA polymerase and DNA ligase Mismatch repair Repair Significance The importance of proper function of repair enzymes is clear from the inherited disorder xeroderma pigmentosum. – These individuals are hypersensitive to sunlight. – In particular, ultraviolet light can produce thymine dimers between adjacent thymine nucleotides. – This buckles the DNA double helix and interferes with DNA replication. – In individuals with this disorder, mutations in their skin cells are left uncorrected and cause skin cancer. Concept 9.2 DNA Replicates Semiconservatively When the last primer is removed, no DNA synthesis occurs because there is no 3′ end to extend—a singlestranded bit of DNA is left at each end. These are cut and the chromosome is slightly shortened after each replication. Telomere replication Limitations in the DNA polymerase create problems for the linear DNA of eukaryotic chromosomes. The usual replication machinery provides no way to complete the 5’ ends of daughter DNA strands. – Repeated rounds of replication produce shorter and shorter DNA molecules Concept 9.2 DNA Replicates Semiconservatively Chromosome ends must be protected from being joined to other chromosomes by the DNA repair system. Telomeres are repetitive sequences at the ends of eukaryotic chromosomes. The repeats bind a protein complex called shelterin, which protects the ends from being joined together. The repeats also form loops, which are also protective. Figure 9.13 Telomeres and Telomerase Telomere The ends of eukaryotic chromosomal DNA molecules, the telomeres, have special nucleotide sequences. – In human telomeres, this sequence is typically TTAGGG, repeated between 100 and 1,000 times. Telomeres protect genes from being eroded through multiple rounds of DNA replication. Eukaryotic cells have evolved a mechanism to restore shortened telomeres. Telomerase uses a short molecule of RNA as a template to extend the 3’ end of the telomere. – There is now room for primase and DNA polymerase to extend the 5’ end. – It does not repair the 3’-end “overhang,” but it does lengthen the telomere. Telomerase Telomerase is not present in most cells of multicellular organisms. Therefore, the DNA of dividing somatic cells and cultured cells does tend to become shorter. Thus, telomere length may be a limiting factor in the life span of certain tissues and the organism. Telomerase is present in germ-line cells, ensuring that zygotes have long telomeres. Active telomerase is also found in cancerous somatic cells. – This overcomes the progressive shortening that would eventually lead to self-destruction of the cancer. Concept 9.2 DNA Replicates Semiconservatively After 20–30 cell divisions, the chromosome ends become too short, the chromosomes lose their integrity, and apoptosis ensues. But continuously dividing cells like bone marrow and gametes maintain their telomeric DNA. – Telomerase catalyzes the addition of lost telomeric sequences. It has an RNA sequence that acts as a template for the telomeric DNA. Concept 9.2 DNA Replicates Semiconservatively Telomere lengths tend to shorten with aging. If a gene expressing high levels of telomerase is added to human cells in culture, their telomeres do not shorten, and the cells become immortal. This is also seen in mice that overexpress telomerase— they live longer. Cancer cells also express telomerase. Concept 9.2 DNA Replicates Semiconservatively Copies of DNA sequences can be made by the polymerase chain reaction (PCR) using: • A double-stranded DNA sample • Two primers complementary to the ends of the sequence to be copied • The four dNTPs • A DNA polymerase that works at high temperatures • Salts and a buffer to maintain pH Concept 9.2 DNA Replicates Semiconservatively PCR is a cyclic process in which a sequence of steps is repeated over and over again. DNA replication is fast, so it takes only a short time to make millions of copies. The sequences at each end of the amplified fragment must be known ahead of time, so that complementary primers can be made. A pair of primers will usually bind to only a single region of DNA in an organism’s genome. Figure 9.15 The Polymerase Chain Reaction Concept 9.3 Mutations Are Heritable Changes in DNA Mutations are changes in the nucleotide sequence of DNA that are passed on from one cell or organism to another. Mutations occur by a variety of processes, including replication errors that are not corrected by repair systems. Concept 9.3 Mutations Are Heritable Changes in DNA Somatic mutations occur in somatic (body) cells. They are passed on by mitosis but not to sexually produced offspring. Germ line mutations occur in germ line cells that give rise to gametes. A gamete with a mutation passes it on to the new organism at fertilization. Mutations may or may not affect the phenotype. Concept 9.3 Mutations Are Heritable Changes in DNA Silent mutations do not affect protein function. Loss of function mutations prevent gene transcription or produce nonfunctional proteins; nearly always recessive. Gain of function mutations lead to a protein with altered function. Usually dominant; common in cancer cells. Figure 9.16 Mutation and Phenotype Concept 9.3 Mutations Are Heritable Changes in DNA Conditional mutations cause phenotypes under restrictive conditions, such as temperature (e.g., point restriction coat color in cats and rabbits). The wild-type phenotype is expressed under other, permissive conditions. Concept 9.3 Mutations Are Heritable Changes in DNA A point mutation results from the gain, loss, or substitution of a single nucleotide. – Can arise from replication errors or be caused by environmental mutagens such as radiation or certain chemicals. Concept 9.3 Mutations Are Heritable Changes in DNA Point mutations may alter the amino acid sequence in a protein with drastic effects. The sickle-cell disease allele differs from the normal by one base pair, resulting in a polypeptide with only one different amino acid. Concept 9.3 Mutations Are Heritable Changes in DNA Point mutations may result in proteins that are less efficient, but maintain enough function that phenotype is not changed. Or amino acid substitutions may not affect protein function (e.g., substitution of one hydrophilic amino acid for another). Concept 9.3 Mutations Are Heritable Changes in DNA The human gene TP53 encodes the tumor suppressor protein p53, which normally inhibits the cell cycle. A gain-of-function point mutation in TP53 causes the protein to promote the cell cycle and prevent cell death— it has a gain of oncogenic function. Concept 9.3 Mutations Are Heritable Changes in DNA Chromosomal mutations are extensive changes in genetic material involving whole chromosomes. They can result from mutagens or drastic errors in replication. They can provide new combinations of genes and genetic diversity important to evolution by natural selection. Concept 9.3 Mutations Are Heritable Changes in DNA Chromosomal mutations: – Deletions—loss of a chromosome segment; can have severe or fatal consequences – Duplications—homologous chromosomes break in different places and recombine with wrong partners; one may have two copies of the segment and the other may have none Concept 9.3 Mutations Are Heritable Changes in DNA Inversions result from breaking and rejoining, but the segment is “flipped.” Translocations—segment of DNA breaks off and is inserted into another chromosome; can lead to duplications and deletions Figure 9.17 Chromosomal Mutations Concept 9.3 Mutations Are Heritable Changes in DNA Spontaneous mutations occur with no outside influence. – Replication errors by DNA polymerase—most are repaired but some become permanent. – Nucleotide bases can exist in 2 forms (tautomers), one common and one rare. A rare tautomer can pair with the wrong base. Figure 9.18 Spontaneous and Induced Mutations (Part 1) Concept 9.3 Mutations Are Heritable Changes in DNA – Spontaneous chemical reactions may change bases (e.g., deamination) – Errors in meiosis such as nondisjunction and aneuploidy or chromosomal breakage and rejoining. – Gene sequences can be disrupted—random chromosome breakage and rejoining can produce deletions, duplications, inversions, or translocations. Concept 9.3 Mutations Are Heritable Changes in DNA Induced mutations are caused by mutagens: • Chemicals can alter nucleotide bases (e.g., nitrous acid can cause deamination) • Some chemicals add other groups to bases (e.g., benzopyrene adds a group to guanine and prevents base pairing). Figure 9.18 Spontaneous and Induced Mutations (Part 2) Concept 9.3 Mutations Are Heritable Changes in DNA – Ionizing radiation, such as X rays, can detach electrons from atoms and form highly reactive free radicals that can change bases and break sugar phosphate bonds. – UV radiation (from sun or tanning lamps) is absorbed by thymine, causing it to form covalent bonds with adjacent nucleotides; disrupts DNA replication. Figure 9.18 Spontaneous and Induced Mutations (Part 3) Concept 9.3 Mutations Are Heritable Changes in DNA DNA sequencing revealed that mutations occur most often at certain base pairs. These “hotspots” are often located where cytosine has been methylated to 5-methylcytosine. If 5-methylcytosine loses an amino acid, it becomes thymine, a natural base for DNA. During mismatch repair, it is repaired correctly only half of the time. Figure 9.19 5-Methylcytosine Is a “Hotspot” for Mutations Concept 9.3 Mutations Are Heritable Changes in DNA Many mutagens are naturally occurring. Plants and fungi make many chemicals for defense; some can be mutagenic, such as aflatoxin made by the mold Aspergillus. Radiation can be natural, such as UV from the sun, or human-made, such as radiation from nuclear bombs. There are about 16,000 DNA-damaging events per cell per day, of which 80% are repaired. Concept 9.3 Mutations Are Heritable Changes in DNA Mutations can have benefits: – Provides the raw material for evolution in the form of genetic diversity – Diversity may benefit the organism immediately—if mutation is in somatic cells – Mutations in germ line cells may cause an advantageous change in offspring Concept 9.3 Mutations Are Heritable Changes in DNA Mutations can be harmful if they result in loss of function of genes or other DNA sequences needed for survival. Harmful mutations in germ line cells can be passed to offspring. – If heterozygotes for the mutation mate and produce a homozygote, the mutation can be lethal. Harmful mutations in somatic cells can lead to cancer. Concept 9.3 Mutations Are Heritable Changes in DNA We try to minimize exposure to mutagens. Many things that cause cancer are mutagens. Benzopyrene is found in coal tar, car exhaust, charbroiled foods, and cigarette smoke. Public policies help reduce exposure: – Bans on cigarette smoking – International treaties banning ozone-depleting chemicals Answer to Opening Question Ancient DNA is usually destroyed in the fossilization process. But intact DNA can be found in frozen specimens and the interior of bones. PCR can amplify tiny amounts of DNA for sequencing, but samples are easily contaminated. Answer to Opening Question The Neanderthal Genome Project has extracted DNA from bones and sequenced the entire genome. The DNA is over 99% identical to human DNA, justifying putting neanderthals in the same genus, Homo. Answer to Opening Question Interesting findings: – Some Neanderthals may have had red hair and fair skin, due to a point mutation in the gene MC1R. – Neanderthals may have been capable of speech, as their vocalization gene FOXP2 was identical to humans. – DNA sequences suggest interbreeding of humans and Neanderthals. Figure 9.20 A Neanderthal Child This reconstruction of a Neanderthal child who lived about 60,000 years ago was made using bones recovered at Gibraltar, as well as phenotypic projections made from DNA analyses.