--maternal age effect: older mothers produce more aneuploid (Down's, etc.) babies than younger mothers. No effect of father's age.

Size: px

Start display at page:

Download "--maternal age effect: older mothers produce more aneuploid (Down's, etc.) babies than younger mothers. No effect of father's age."

Victor Summers
6 years ago
Views:

1 Chromosomes --each gene makes a protein. A gene is just a region of the DNA on the chromosome, not different from any other part of the chromosome. Humans have about 30,000 genes. The location of a gene is not related to its function. Each gene has a fixed location on the chromosome. --humans have 46 chromosomes. 44 (22 pairs) are autosomes (non-sex chromosomes, any chromosome except the X and Y). also have sex chromosomes: X and Y. if you have a Y chromosome you are male; no Y makes you female. For normal people, males have one X and one Y, while females have 2 X chromosomes. -- sex determination in humans: the Y chromosome has very few genes on it, but it has the critical SRY gene on it. If this gene is present, testes form in the embryo. The testes secrete the hormone testosterone, which causes the embryo to develop as a male. If SRY is absent (or inactivated) ovaries form instead. Thus, rare XY females have an inactivated SRY gene, and rare XX males have a SRY gene that has been moved to the X. --abnormal numbers of chromosomes. polyploidy is having whole extra sets of chromosomes. Example of triploid, a polyploid with 3 sets of chromosomes instead of 2. In humans triploids are lethal, but in many species triploids live but are sterile: source of seedless fruit. --extra or missing a single chromosome = aneuploid. Caused by meiosis problems: 2 chromosomes go to same pole instead of opposite poles. Aneuploidy is bad: gene numbers are out of balance. --sex chromosome aneuploidies. --XXY: Klinefelter's syndrome: feminized male --XO (only 1 X): Turner's syndrome. female but no ovaries, so sterile, --XYY: male, but slight problems: acne, reduced intelligence, tall --XXX: female, normal (but XXXX, etc. is retarded) --autosomal aneuploidies: all occur, but most die before birth, including all where1 chromosome is missing. --Down syndrome: 3 copies of chromosome 21. Survive to adulthood, but retarded, heart defects, characteristic appearance. The most common form of mental retardation --maternal age effect: older mothers produce more aneuploid (Down's, etc.) babies than younger mothers. No effect of father's age. --structural changes in chromsomes, such as inversions and translocation can cause problems for 2 reasons: 1. creating a structural change means breaking a chromosome, which often means destroying a gene necessary for life. 2. chromosomes with structural changes often have trouble completing meiosis, resulting in aneuploid gametes. --translocational Down syndrome is caused by a translocation involving chromosome 21. Unlike regular Down syndrome, translocational Down's is inherited. --sex linkage: genes on the X chromosome are called sex-linked. Genes on other chromosomes are autosomal. The X has many genes, just like any other chromosome. However, the Y has few genes. So, males with only 1 X express every allele on their X chromosome, whether dominant or recessive. Females have 2 X's. so a recessive mutant allele is usually covered up by the dominant normal allele. This makes sex-linked traits much more common in males than in females. --red/green colorblindness. We have 3 color receptors in our eyes: red, green, and blue. The red and green color receptor genes are on the X. Either or both can be inactivated, leading to various forms of colorblindness. The blue receptor is on an autosome and is only rarely affected. --hemophilia. Blood clots on exposure to air due to clotting proteins. The genes for these proteins are on the X, and when they are inactivated the blood doesn't clot. Leads to bleeding to death. 1

2 --sex-linked inheritance patterns. Sons get their X from their mother (and Y from father). The father's X ends up in his daughters but not his sons. The offspring of a cross depend on the sexes of the mutant and normal parents. --Colorblind male x normal female. Offspring all normal: males get normal X from mother, and females have a normal X from mother and a colorblind X from father (the daughters are heterozygotes, or carriers, of the colorblind trait). --Normal male x colorblind female. The male offspring are all colorblind, since their X came from the mother. The female offspring are all normal, with a normal X from the father and a colorblind X from the mother. They are heterozygotes. --sex-influenced traits: not sex-linked, not on the X chromosome. Due to differences in dominance between the sexes. Example of male pattern baldness: Being homozygous for the bald allele makes you bald no matter which sex. But, the heterozygotes are different: a male heterozygote is bald, but a female heterozygote had normal hair. DNA --an experiment showing that DNA is the hereditary material, the physical carrier of the instructions needed to build an organism: bacterial infections of mice. Streptococcus bacteria kill mice with pneumonia when injected. Two strains of bacteria: S: smooth colonies, polysaccharide coat, kills the mice; and R: rough colonies, no coat, mice survive. If you mix dead S with live R and inject, the mice die, and the R bacteria are converted to S. Some property is transmitted from the dead S to the live R. By trying different components of the dead S bacteria, it was found that DNA was what caused the change in the R bacteria. --structure of DNA, based on Watson and Crick, early 1950's. --DNA is composed of nucleotides, which consist of a sugar, phosphate, and a base. There are 4 possible bases: adenine (A), guanine (G), thymine (T), and cytosine (C). Since A pairs with T and G pairs with C in the DNA, the amount of A always equals the amount of T, and the amount of G always equals the amount of C. --the DNA molecule has 2 backbones wound around each other. The backbones consist of alternating sugars and phosphates. The bases stick into the center of the molecule, and are paired with each other, A with T, G with C. Thus if you know the bases on one strand, you can easily determine the bases on the other strand. --the 2 DNA strands are anti-parallel: they run in opposite direction --the two strands are twisted tougher into a helix. --replication of DNA: it is semi-conservative: going from 1 DNA molecule to 2 DNA molecules, each new DNA has one strand from the original molecule and one new strand. The enzyme DNA polymerase forms the new strand using the old strand as a template. The raw materials are nucleotides with 3 phosphates on them. These work like ATP does: removing the 2 end phosphates provides energy to cause the DNA synthesis reaction to proceed. --genes are expressed by: 1. transcription of the gene (which is DNA) into an RNA copy called messenger RNA (mrna). 2. processing the mrna and transporting it from the nucleus to the cytoplasm 3. translation of the mrna into protein --RNA and DNA are both nucleic acids. RNA differs from DNA in several ways: 1. RNA uses ribose as its sugar, while DNA uses deoxyribose 2. RNA uses the base uracil (U) where DNA uses the base thymine (T) 3. RNA is single stranded; DNA is double stranded 4. RNA molecules are short, on gene long, while DNA is very long and contains many genes --Types of RNA: 2

3 1. messenger RNA (mrna): copy of a single gene 2. transfer RNA (trna): adapter between mrna and amino acids during translation 3. ribosomal RNA: part of the ribosome (molecular machine that translates mrna into protein) --transcription. Making an RNA copy of a gene. Occurs in the nucleus. The enzyme RNA polymerase binds to the promoter at the beginning of the gene, then copies the gene, starting at 5' end and moving to the 3' end. Nucleotides with 3 phosphates are the raw materials: 2 of the phosphates are removed to generate the energy needed for the reaction. --RNA processing: Only occurs in eukaryotes, not prokaryotes. add protection to the ends of the mrna: a cap at one end and a poly A tail to the other end. Also splice out introns, which are DNA sequences found within a gene that don't code for protein. Introns have no known function: just junk to be removed before the RNA can be translated into protein. --genetic code: each group of 3 bases in the mrna is a codon; each codon codes for 1 amino acid. There are 64 codons: 3 of them code for nothing (stop codons), which signals the end of the protein. The rest code for the 20 different amino acids. Usually more than 1 codon codes for the same amino acid. --translation: the ribosome is a protein/rna hybrid structure that converts RNA into protein. Transfer RNA molecules have 3 bases called the anti-codon that match the 3 bases of a codon on the mrna. On the other end of the trna the proper amino acid is attached. The first step in translation is initiation, in which the ribosome binds to the beginning (the 5' end) of the mrna, then moves down the mrna to the start codon, which is always AUG. The second step is elongation, in which trna molecules bind to each codon in turn, transferring their amino acids to the growing protein chain; this process is catalyzed by the ribosome, which is moving down the messenger RNA one codon at a time. Last comes termination, which occurs when the ribosome reaches a stop codon, where it falls off with the help of a protein called releasing factor, releasing the new protein. The protein then folds up spontaneously into its active configuration. --mutations: a mutation is any change in the DNA base sequence. Most mutations have no effect, because they occur outside the genes. Within a gene, some mutations have no effect on the protein made by that gene, some mutations have only a small effect, and other mutations destroy the protein. --mutations in most cells of the body only affect that individual: the worst effect is cancer. Mutations that affect the sperm and egg producing cells: germ-line mutations can affect future generations. --mutations can be caused by UV light, radiation, or certain chemicals. Things which cause mutations also cause cancer (because cancer is caused by mutations). --all cells within the body have the same genes. What makes cells different from one another is which genes are on and which are off. When a gene is making mrna it is on; when it is not making mrna it is off. --a good model for gene regulation is the lac gene (operon) in the common gut bacterium E. coli. The lac gene makes an enzyme that digests lactose (milk sugar). The gene needs to be on only when lactose is present, and off when lactose is absent. When the lac gene is on, RNA polymerase binds to the lac gene promoter and transcribes a copy of the gene. This copy is then translated into the protein. When the lac gene is off, RNA polymerase is prevented from binding to the promoter, so no transcription occurs. --the mechanism of control is another protein, the lac repressor protein. The repressor binds to a region of DNA next to the promoter; when the repressor is bound to the DNA, it physically blocks RNA polymerase from binding to the promoter. --However, the repressor can also bind to lactose, but it can't bind to both lactose and the DNA at the same time. So, when lactose is present, the repressor binds to lactose and not to the DNA. This allows RNA polymerase to bind to the promoter and transcribe the gene. When lactose is absent, the repressor binds to the DNA instead, preventing transcription. 3

4 --in mammals, only 1 X chromosome is active in each cell. In females (XX), one of the X's is converted into an inactive Barr body. This happens when the embryo has about 200 cells, and it happens in each cell independently of the others. The inactive X stays inactive throughout life. This is the cause of tortiseshell and calico cats: they are heterozygous for a coat color gene on the X: one allele makes black fur and the other allele makes orange fur. The different colored patches form depending on which allele is on the active X in those cells. --hormones can be either steroids (lipids with 4 rings of carbon atoms) or peptides (short proteins). Hormones cause changes in cells by stimulating the transcription of specific groups of genes. --recombinant DNA technology: taking genes out of a living organism, manipulating them in the test tube, then putting them back into a living organism. Used to make lots of some specific gene or the gene's protein products. --to get foreign DNA to replicate inside a bacterial cell, you need to insert it into a small circle of DNA that can replicate independently of the chromosome called a plasmid. To do this, the foreign DNA (the gene you want to clone) and the plasmid DNA both need to be cut with a restriction enzyme, an enzyme that cuts DNA only at a specific base sequence. Once the 2 DNAs have been cut, they can be mixed together and re-attached into 1 big circle using the enzyme DNA ligase. DNA ligase joins 2 DNA molecules together, forming a recombinant DNA molecule. Finally, the recombinant DNA is put back into the living cells through the process of transformation. Transformation can be done by pulsing the bacteria with electricity or by chemical treatments. You can then grow as much of the bacteria (and the gene you have cloned) as you like. --nuclear cloning involves taking the nucleus from a body cell and transplanting it into an egg cell that has had its nucleus removed. Theoretically, this egg will develop into an individual genetically identical to the source of the nucleus. During development, cells in the embryo start out totipotent: able to become any type of cell in the body. However, as development proceeds, the DNA in body cells is permanently modified in ways that make it unable to become different cell types: most body cells are no longer totipotent. Evolution --age of the Earth is about 4.6 billion years. Known through radioactive dating: the rate at which isotopes convert from one type to another doesn't change regardless of external conditions, so they can be used as clocks. Geology also shows the results of events that took a very long time to occur, such as mountain building and sea sediment deposits. Geological evidence is based on the principle of uniformity: the rocks we see got here by the same processes we can see at work today: erosion, volcanism, etc. --potassium-argon dating: potassium-40 (atomic weight = 40) is radioactive and decays very slowly into argon-40. The rate of decay is constant, and it is not affected by external conditions at all. Potassium is a common component of volcanic rocks, and argon is a gas. When a volcano erupts molten rock, all the argon in it is released into the atmosphere, leaving the potassium behind: the clock is reset. Over time, the potassium decays into argon, which is trapped in the rock.. It is possible to determine the ratio of potassium-40 to argon-40 in the rock, which then tells you how long ago the rock was melted. Bones lying between layers of volcanic rock are dated this way. The dating is calibrated using tree rings, which are laid down every year and can be correlated into a chronology going back 9000 years in some places. --evidence for changes in species over time (evolution): fossils (pieces of ancient life forms that have been converted to rock) can be seen to get more complex and change type as one moves up the layers of rock towards the present. --Lamarck had the incorrect view that changes in an organism's body duirng its lifetime could be passed on to its offspring. This view called inheritance of acquired characteristics, is not true: only random changes occur in DNA. 4

5 --Darwin's (1860's) big idea: evolution through natural selection. Natural selection is the idea that those individuals which survive and reproduce better that other members of their species end up with more descendants. After a while, the genes of the more fit individuals (more fit = able to survive and reproduce better) some to dominate the population. This causes a general increase in the fitness of the species, and it gradually changes the species as seen in the fossil record. Artificial selection works similarly, except that humans consciously choose which individuals will be allowed to survive and reproduce. -- A population is a group of individuals of a single species that lives in the same area and interacts with each other. A population shares a gene pool, the collection of all the genes and alleles present in the population. Microevolution is the gradual change in the frequency of those various alleles in the gene pool. Microevolution is changes within a species, not between species. Individuals don't' evolve, only populations evolve, which means that the genes within each individual are fixed, but which individuals contribute to the next generation is influenced by various factors that contribute to evolution. --Hardy-Weinberg equilibrium: under ideal conditions, the frequencies of different genotypes (AA, Aa, aa) can be calculated from the allele frequencies (A and a). If the genotype frequencies in a population don't match the frequencies calculated by the Hardy-Weinberg rule, the population is said to not be in equilibrium, because one of the following 5 conditions is not met: 1. no natural selection: all alleles and genotypes have equal fitness 2. the population must be very large 3. no migration of individuals coming in from other populations of the species 4. no mutations 5. matings must occur randomly --none of these conditions is completely realistic. --types of natural selection: --directional selection: one extreme of a trait is favored over the others. Causes the population average to shift towards the more fit form. --stabilizing selection: the average type is more fit than either extreme: keeps the population close to the average type by selecting against the extremes. --disruptive selection: the average type is the least fit and the extremes are the most fit. Causes teh population to split into 2 different types. --sexual selection: traits that cause an individual to be more attractive to members of the opposite sex tend to evolve very quickly. --genetic drift is random changes in gene frequency. Especially in small populations, random events: who survives natural disasters, who mates with who, etc., can have big effects on the gene frequencies. This is the basis for the founder effect: the initial members of a new population can cause it to look significantly different from the original population. Also the bottleneck effect: if a population is reduced to a very small number of individuals, the population will look quite different from the original population once it recovers from its low point. Genetic drift is an important cause of evolutionary change that does not involve natural selection. --small populations often suffer from a lack of genetic diversity, which can easily lead to extinction. Inbreeding: when close relatives mate, recessive lethal mutations often become homozygous because they were inherited from both parents. Speciation --a species can be defined by the biological species concept: a species is a group of individuals that freely interbreeds under natural conditions. Forced breeding under human-controlled conditions doesn't count. An older method of defining species is the morphological species concept: all members of a species look similar to one another. --species are kept separate by reproductive isolating mechanisms, which prevent the appearance of fit and fertile offspring. Isolating mechanisms can be physical, such as the inability of the sperm of one species to fertilize the egg of another species, or the inability of a hybrid embryo to develop. Sometimes sterile 5

6 offspring (such as a mule, the cross between a horse and a donkey) appear in interspecies crosses. Some reproductive isolating mechanisms are more psychological in nature: individuals of different species don't look or smell right to each other, or don't engage in the proper courtship rituals. Other isolating mechanisms involve living or mating in different places or seasons. --speciation is the process of splitting one species into 2 species. It is the basic event of evolution. The most common mechanism is allopatric speciation: 2 populations of the species are isolated completely from each other, usually by a geographical barrier like mountains or a river. The two populations then have independent mutations, genetic drift, natural selection (especially sexual selection). If the two populations then meet, their gene pools will have changed sufficiently so that they will no longer mate successfully with one another. --in some cases, a species splits into 2 species without a physical separation: sympatric speciation. One way this can occur is a doubling of the genome: one group becomes polyploid. In specific, if a small number of individuals become tetraploid, they will be unable to mate successfully with diploid individuals, because the offspring of such a cross would be triploid, which is sterile. --sometimes two groups of a species are separated, and then come back into contact with one another at a hybrid zone. In this case, the two groups may merge back into a single species, or they may develop mechanisms to stay isolated from each other. In this case, they become 2 species by parapatric speciation. --after a new species forms, it may survive and change gradually over long periods of time as a single species. Alternatively, it may go through an adaptive radiation: a sudden burst of speciation in which many similar species arise from a single species in a fairly short time. This often happens when an isolated island is reached: there are lots of potential niches for new species to inhabit and no competitors. The third thing that can happen to a species is that it can go extinct: have no members left. All species eventually go extinct. 6

UNIT MOLECULAR GENETICS AND BIOTECHNOLOGY

UNIT MOLECULAR GENETICS AND BIOTECHNOLOGY Standard B-4: The student will demonstrate an understanding of the molecular basis of heredity. B-4.1-4,8,9 Effective June 2008 All Indicators in Standard B-4