Human Biology BIOL 104 Talk Twelve Genetics and

Human Biology (BIOL 104) Talk Twelve: Genetics and DNA Mendel's Experiments and Heredity (Chapter 12) DNA Structure and Function (Chapter 14) Genes and Proteins (Chapter 15)

Basic Concepts of Heredity • Genetics is the study of genes. Genes provide the instructions for all human traits, including physical features and how body parts function • Each person inherits a particular mix of maternal and paternal genes • Inheritance is how traits, or characteristics, are passed on from generation to generation. • Gregor Mendel is considered “The Father of Genetics“ • Understood that there was something that carried traits from one generation to the next– He called it a “FACTOR”. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Mendel was fortunate he chose the Garden Pea • Mendel probably chose to work with peas because they are available in many varieties. • The use of peas also gave Mendel strict control over which plants mated. • Fortunately, the pea traits are distinct and were clearly contrasting. From the wikimedia free licensed media file repository

Mendelian Genetics • Dominant traits- traits that are expressed. • Recessive traits- traits that are covered up. • Alleles- the different forms of a characteristic. • Punnett Squares- show crosses are made. • Probability- the chances/ percentages that something will occur. • Genotype- the types of genes (Alleles) present. • Phenotype- what it looks like. • Homozygous- two of the same alleles. • Heterozygous- two different alleles.

Mendelian Crosses • Plants used in first-generation crosses were called P 0, or parental generation one, plants • Mendel collected the seeds belonging to the P 0 plants that resulted from each cross and grew them the following season. • These offspring were called the F 1, or the first filial (filial = offspring, daughter or son), generation. • Once Mendel examined the characteristics • in the F 1 generation of plants, he allowed them to self-fertilize naturally. • He then collected and grew the seeds from the F 1 plants to produce the F 2, or second filial, generation. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Mendelian Crosses • Mendel crossed plants that were true-breeding for violet flower color with plants true-breeding for white flower color (the P generation). • The resulting hybrids in the F 1 • generation all had violet flowers. • In the F 2 generation, approximately three quarters of the plants (705) had violet flowers, and one quarter (224) had white flowers. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

The Punnett Square Approach for a Monohybrid Cross Monohybrid cross: • When fertilization occurs between two truebreeding parents that differ in only one characteristic • Mendel postulated that each parent in the monohybrid cross contributed one of two paired unit factors to each offspring, and every possible combination of unit factors was equally likely. • Punnett square predicts the possible outcomes of a genetic cross or mating and their expected • frequencies. • Uppercase and lowercase letters represent dominant and recessive alleles. • • • VV - homozygous dominant violet flowers vv - homozygous recessive white flowers Vv - heterozygous with violet flowers Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

The Punnett Square Approach for a Monohybrid Cross • For a monohybrid cross of two truebreeding parents, each parent contributes one type of allele. Only one genotype is possible. • All offspring are Yy and have yellow seeds. • In a self-cross of one of the (F 1) Yy heterozygous offspring, the ( F 2) offspring potentially have one of four possible allele combinations: YY, Yy, y. Y, or yy • Because fertilization is a random event, each combination will be equally likely and for the offspring to exhibit a ratio of YY: Yy: yy genotype of 1: 2: 1 • As the YY and Yy offspring have yellow seeds and are phenotypically identical, offspring exhibit a phenotypic ratio of 3 yellow: 1 green. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

The Test Cross Distinguishes the Dominant Test cross: Phenotype • Mendel also developed a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote. • The dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic. • If a homozygote, then all F 1 offspring will be heterozygotes expressing the dominant trait • Alternatively, if a heterozygote, the F 1 offspring will exhibit a 1: 1 ratio of heterozygotes and recessive homozygotes • The test cross further validates Mendel’s postulate that pairs of unit factors segregate equally. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Mendel studies seven characteristics in the garden pea : Statistics indicated a pattern. From the wikimedia free licensed media file repository

Basic Concepts of Heredity • There alternative forms of genes, now called alleles • For each character, an organism inherits two alleles, one from each parent • Gametes carry only one allele for each inherited characteristic • Alleles can be dominant or recessive • Homozygous dominant (AA) • Homozygous recessive (aa) • Heterozygous (Aa) • Genotype: Inherited alleles • Phenotype: Observable functional or physical traits A A pair of homologous chromosomes, each in the unduplicated state (most often, one from a male parent and its partner from a female parent) B A gene locus (plural, loci), the location for a specific gene on a specific type of chromosome C A pair of alleles (each being one chemical form of a gene) at corresponding loci on a pair of homologous chromosomes D Three pairs of genes (at three loci on this pair of homologous chromosomes); same thing as three pairs of alleles

Pedigree analysis reveals Mendelian patterns in human inheritance From the wikimedia free licensed media file repository • In these family trees, squares symbolize males and circles represent females. • A horizontal line connecting a male and female (--) indicates a mating, with offspring listed below in their order of birth, from left to right. • Shaded symbols stand for individuals with the trait being traced.

Genes can lead to inherited diseases • Humans have ~21, 500 which provide the chemical instructions for building proteins. • Autosomal chromosomes are 22 pairs of chromosomes which are not the X or Y chromosome Recessive: • A term applied to a trait that is only expressed when the second allele is the same. • When both parents are carriers, there is a 25% risk of giving birth to an affected child with each pregnancy. – The affected child would have received a mutated copy of the gene from each parent Dominant: • A term applied to the trait (allele) that is expressed regardless of the second allele. • A mutation in either of an individual's two copies of a gene. – This means a child of an affected person typically has a 50% chance of inheriting the disease. Used with permission from the MAYO Foundation for Medical Education

Autosomal Recessive Disorders Tay-Sachs Disease: • Results from mutations in the HEXA gene on chromosome 15. • HEXA codes for the alpha-subunit of beta-Nacetylhexosaminidase A. This is a hydrolytic enzyme present in lysosomes, which breaks down gangliosides. • Disorder causing gangliosides to accumulate in lysosomes and ultimately make the ganglion cells in the nervous system swell enormously, disturbing the normal functions of neurons. • Classified into three forms, based on the onset age of neurological symptoms. All result in a relentless deterioration of mental and physical abilities before it becomes fatal • In the United States, about 1 in 30 Ashkenazi Jews is a recessive carrier. From the wikimedia free licensed media file repository

Autosomal Recessive Disorders Cystic Fibrosis (CF): • Affects mostly lungs, pancreas, liver, intestines, sinuses, and sex organs. • Caused by the presence of mutations in both copies of the CFTR gene found on chromosome 7 • Codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein – required for proper function of the chloride ion channels important in creating sweat, digestive juices, and mucus. • The accumulation of more viscous, nutrient-rich mucus in the lungs allows bacteria to hide from the body's immune system, causing repeated respiratory infections. • About one in 3, 300 Caucasian children in the United States was born with CF. From the wikimedia free licensed media file repository Image credit: Genome Research Limited

Autosomal Recessive Disorders Phenylketonuria (PKU): • • Caused by a mutation in the gene for hepatic enzyme phenylalanine hydroxylase (PAH) on chromosome 12 Required to breakdown the aromatic side-chain of phenylalanine (Phe) to generate tyrosine. When PAH inactive - phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone) • Without treatment, permanent intellectual disability occurs. Seizures, behavioral problems, and psychiatric disorders are also common. • Reducing intake of Phe in diet is a effective treatment (no fish, peanuts, egg white). The sweetener aspartame, present in many diet foods and soft drinks, must also be avoided. – • it is metabolized into phenylalanine. In the United States Caucasians are affected at a rate of 1 in 10, 000. From the wikimedia free licensed media file repository

Autosomal Dominant Disorders Neurofibromatosis (NF): • Two types, governed by malfunctions in separate genes. • NF 1: Gene is located on chromosome 17. This gene normally produces a protein called neurofibromin. The mutated gene causes a loss of neurofibromin, which allows cells to grow uncontrolled. • Common symptoms: Learning disabilities, tan spots, vision disorders, mental disabilities, and epilepsy • NF 2: Gene is located on chromosome 22, and produces a protein call merlin. The mutated gene causes a loss of merlin, leading to uncontrolled cell growth. • Symptoms: Symmetric, benign brain tumors, tumors of the inner ear, and (less common) of the major bones and joints. • In the United States, about 1 in 3, 500 people have NF 1 and 1 in 25, 000 have NF 2. – Males and females are affected equally frequently. From the wikimedia free licensed media file repository

Autosomal Dominant Disorders Huntington Disease (HD): • Result in a mutation of the HTT gene found on chromosome 4 that codes for the protein Huntington (HTT). Facilitates vesicular transport and synaptic transmission and neuronal gene transcription. • In humans the disruption of the normal gene does not itself cause the disease. It is thought that the disease is not caused a lack of production of HTT, but by an increase in the toxic function of the mutated form of the protein (m. HTT) in the body. • Results in movement, thinking (cognitive) and psychiatric disorders. Develop signs and symptoms in their 30 s or 40 s. But the disease may emerge earlier or later in life. • The worldwide occurrence is 5– 10 in 100, 000 – varies greatly geographically due to ethnicity, local migration and past immigration pattern From the wikimedia free licensed media file repository

Human Sex-linked Disorders • X-linked recessive disorders in Humans include red-green color blindness, and Types A and B hemophilia. • As males need to inherit only one recessive mutant X allele to be affected disorders are disproportionately observed in males. • Females must inherit recessive X-linked alleles from both of their parents in order to express the trait. • When they inherit one recessive Xlinked mutant allele and one dominant Xlinked wild-type allele, they are carriers of the trait and are typically unaffected. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Human Sex-linked Disorders • Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. • However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, • Or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait. • Although some Y-linked recessive disorders exist, typically they are associated with infertility in males and are therefore not transmitted to subsequent generations. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA structure and replication

DNA: A Double Helix • The building blocks of DNA are nucleotides. The important components of the nucleotide are a nitrogenous base, deoxyribose (5 -carbon sugar), and a phosphate group. • The nucleotide is named depending on the nitrogenous base. The nitrogenous base can be a purine such as adenine (A) and guanine (G), or a pyrimidine such as cytosine (C) and thymine (T). • • • Assuming there is no error: Adenine (A) base pairs with thymine (T) Guanine (G) base pairs with Cytosine (C) Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA: A Double Helix • DNA is made up of two strands that are twisted around each other to form a right-handed helix. • The base pairs are stabilized by hydrogen bonds; adenine and thymine form two hydrogen bonds and cytosine and guanine form three hydrogen bonds. • The two strands are anti-parallel in nature; that is, the 3' end of one strand faces the 5' end of the other strand. • The sugar and phosphate of the nucleotides form the backbone of the structure, whereas the nitrogenous bases are stacked inside. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Basics of DNA Replication • The Watson and Crick model suggested a way in which DNA could be replicated during cell division. • Basically, the two strands unwind and separate where the hydrogen bonds connect the nucleotides. Each parental strand then serves as a template for a new, complementary daughter strand. • Replication is said to be semiconservative because the original information encoded in each parental strand is conserved (kept) in the daughter molecules. • Thus, a newly replicated molecule of DNA consists of one “old” strand one “new” strand. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Replication in Eukaryotes • DNA is bound to basic proteins known as histones to form structures called nucleosomes. • The chromatin (the complex between DNA and proteins) may undergo some chemical modifications, so that the DNA may be able to slide off the proteins or be accessible to the enzymes of the DNA replication machinery. • At the origin of replication, a prereplication complex is made with other initiator proteins. • Other proteins are then recruited to start the replication process. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Replication in Eukaryotes • A helicase opens up the DNA helix. • Replication forks are formed at each replication origin as the DNA unwinds. The opening of the double helix causes overwinding, in the DNA ahead of the replication fork. • A primer is required to initiate synthesis, which is then extended by DNA polymerase as it adds nucleotides one by one to the growing chain. • The leading strand (3' to 5') is synthesized continuously, whereas the lagging strand (5' to 3') is synthesized in short stretches called Okazaki fragments. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Replication in Eukaryotes • The RNA primers are replaced with DNA nucleotides; the DNA remains one continuous strand by linking the DNA fragments with DNA ligase. • The ends of the chromosomes pose a problem as polymerase is unable to extend them without a primer. • Telomerase, an enzyme with an inbuilt RNA template, extends the ends by copying the RNA template and extending one end of the chromosome. • DNA polymerase can then extend the DNA using the primer • In this way, the ends of the chromosomes are protected. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Replication in Eukaryotes • When the replication fork reaches the end of the linear chromosome, there is no place for a primer to be made for the DNA fragment to be copied at the end of the chromosome. • Remain unpaired, and over time get progressively shorter as cells continue to divide. • The ends known as telomeres, which have repetitive sequences that code for no particular gene. – In a way, these telomeres protect the genes from getting deleted as cells continue to divide Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Replication in Eukaryotes • The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and complementary bases to the RNA template are added - ends of the chromosomes are replicated. • Cells that undergo cell division continue to have their telomeres shortened because most somatic cells do not make telomerase. – This essentially means that telomere shortening is associated with aging. • Telomerase is typically active in germ cells and adult stem cells. It is not active in adult somatic cells. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA Repair and mutations • • DNA replication is a highly accurate process, but mistakes can occasionally occur Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. • Proofreading: The polymerase checks whether the newly added base has paired correctly with the base in the template strand. • If it is the right base, the next nucleotide is added. • If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. • Mismatch repair: The incorrectly added base is detected after replication. • The mismatch repair proteins detect this base and remove it from the newly synthesized strand by nuclease action. • The gap is now filled with the correctly paired base. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA mutations • In rare cases, mistakes not corrected, leading to mutations – in other cases, repair enzymes are themselves mutated or defective Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

The Central Dogma

The Central Dogma: DNA Encodes RNA; RNA Encodes Protein Transcription - DNA is decoded into RNA • Gene serves as a template for RNA synthesis. Process occurs in the nucleus using RNA polymerases • • • Begins at “promoter” region 5' capped end for protection and binding to the ribosome Joins nucleotides together until a termination sequence is reached RNA Processing “Pre-m. RNA”: contains introns and exons • Exons: sequences for the proteins Translation • t. RNA brings in an amino acid in an order coded for by the three nucleotide triplet code (Codon). Protein is made in the ribosome. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA into RNA: The First Step in Making Proteins • Eukaryotes require three proteins, called transcription factors, to first bind to the promoter region and then help recruit the appropriate polymerase. • During elongation, the RNA polymerase tracks along the DNA template, synthesizes m. RNA in the 5' to 3' direction, and unwinds and rewinds the DNA as it is read. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

RNA Processing in Eukaryotes Eukaryotic genes are composed of: • Exons, protein-coding sequences that are expressed • Introns intervening sequences which may be involved in gene regulation • Pre-m. RNA splicing involves the precise removal of introns from the primary RNA transcript. • The splicing process is catalyzed by protein complexes called spliceosomes that are composed of proteins and RNA molecules called sn. RNAs. • Spliceosomes recognize sequences at the 5' and 3' end of the intron. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA into RNA: The First Step in Making Proteins Gene transcription can be turned on or off. • Each cell determines which genes are active or inactive – Some genes switched on and off throughout a person’s lifetime – Some turned on only at certain times – Some turned off permanently before birth • Regulatory proteins – Speed up or halt transcription – May bind with noncoding DNA sequences and affect the transcription of a neighboring gene

The Genetic Code Codons: • Three nucleotide bases on m. RNA • Sixty-four codons make up the genetic code • Most amino acids have more than one codon Start codon: AUG • Establishes the “reading frame” for translation Stop codons: UAA, UAG, and UGA Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

t. RNA • Has a “hook” for the attachment of an amino acid • Anticodon base pairs with the codon • Sixty-four codons; fewer t. RNAs, due to redundancy of the genetic code • Example – The amino acid proline is coded for by four codons: • CCU • CCC • CCA • CCG Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Ribosomes • Structures responsible for protein synthesis. • Either float freely in the cytoplasm or attached to the cytoplasmic side of the plasma membrane or the cytoplasmic side of the endoplasmic reticulum and the outer membrane of the nuclear envelope • Protein synthesis is an essential function of all cells (including enzymes, hormones, antibodies, pigments, structural components, and surface receptors), ribosomes are found in practically every cell. • Abundant in cells that synthesize large amounts of protein. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Translation • Translation begins when an initiator t. RNA anticodon recognizes a codon on m. RNA. • The large ribosomal subunit joins the small subunit, and a second t. RNA is recruited. • As the m. RNA moves relative to the ribosome, the polypeptide chain is formed. • Entry of a release factor into the A site terminates translation and the components dissociate. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Human Variation • With origins in Africa, modern man has spread around the globe. • In doing so, modern man adapted to the surroundings. From the wikimedia free licensed media file repository

Human Variation • Arms and legs are longer and thinner in warm areas of the planet – shorter and thicker in cold regions. • Conserves heat in cold regions by reducing surface area • Skin pigmentation is darker the nearer the equator to protect the skin from UV. From the wikimedia free licensed media file repository

Polygenic Inheritance • The additive effects of two or more genes on a single phenotype Polygenic inheritance Single trait (e. g. , skin color) Multiple genes From the wikimedia free licensed media file repository

Human Variation • There is a gradient of melanosome size and number in dark, intermediate, and light skin; in addition, melanosomes of dark skin are more widely dispersed. • This diagram is based on one published by Sturm et al. (1998) and summarizes data from Szabo et al. (1969), Toda et al. (1972), and Konrad and Wolff (1973) based on individuals whose recent ancestors were from Africa, Asia, or Europe. PLo. S Biology | http: //biology. plosjournals. org

Human Variation • A traditional skin color map by based on geographical location on a global scale. Taken from: PLo. S Biology | http: //biology. plosjournals. org

Polygenic Inheritance aabbcc (very light) AABBCC (very dark) • Three genes inherited separately Aa. Bb. Cc • The dark-skin allele for each gene (A, B, and C) contributes one “unit” of darkness to the phenotype and is incompletely dominant to the other alleles (a, b, and c). Eggs Aa. Bb. Cc Sperm • An AABBCC person would have very dark skin • An aabbcc person would have very light skin From the wikimedia free licensed media file repository

Ice age Europe (18, 000 years ago) • Glacial ice 2 km thick covers much of Northern Europe and the Alps. • Sea levels are approx. 125 m lower than today and the coastline differs slightly from the present day. • Human populations that began their migration from Africa 60, 000 years earlier were stopped by the ice. From the wikimedia free licensed media file repository

Ice age Europe (18, 000 years ago) • Due to the cold and the need for food, the populations of the day waited the ice age out in the three locations shown on the map. • These were the Iberian Peninsula, the Balkans and the Ukraine. From the wikimedia free licensed media file repository

After the Ice age – 12, 000 years ago • 12, 000 years ago, the ice retreated and the land has become much more supportive to life. • The three groups of humans had taken refuge for so long their DNA had naturally picked up mutations • These three major population groups account for approx 80% of Europe's present-day population From the wikimedia free licensed media file repository

Finally, from 8, 000 years ago • Peoples from Africa that had moved to the Middle East developed the new technology of agriculture and began moving back into Europe. • This was the last migration of human population into Europe. • Body shape and skin pigmentation all changed due to environmental pressure on the genomes of these separate populations From the wikimedia free licensed media file repository

The concept of racism • Racism has many meanings: – All of them come down to the belief that some group of people are better than others. • In most cases, the motivation to conquer a region comes first, the racist ideology comes later • Came about because people thought that a different genetic trait was inferior to one(s) they processed.

The concept of racism • They also believed that their “group identity” was inherited and could not be changed – A view which has no basis in genetics • In the 1940’s the Nazis exterminated 11 million Jews, gypsies and other groups – But not before theses groups were declared “inferior”. • Most people now regard racism as unethical – Denies basic human rights, results in crime and human conflicts.

Central High School in Little Rock, Ark. 1957. Elizabeth Eckford : Used with permission from the media file repository of USHistory. com

Systemic Power and Race • P 3 = power X Power • Power 1 = Power over people of color • Power 2 = Power which gives and preserves privilege and advantages for white people • Power 3 = Power which socializes all of us into the racial rules • Racism’s ultimate power – to control and racialize all of us

The concept of racism • Human populations have always been variable. – adapt and change under selective pressure • Skin pigmentation is determined by a selective environmental pressure due to the total amount of sunlight a population exists with. • Taught hatred for different populations of people

Final thought……

The end! Any Questions?