BICD 100 - Lecture notes 1-11 PDF

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professor Keefe Reuther ...

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Lecture 2 Genetics - The study of heredity and the variation of inherited characteristics in population - Modern biology = the modern synthesis - 1936-1947 - Brought together genetics evolution and molecular cell biology Evolution - A change in genetic composition (allele frequency) of a population over time - Microevolution is within a species Allele - A specific variant of a gene. Different individuals of a species have the same genes but may have different alleles Gene - Sequence of dna that codes for something - Genes make proteins - Length and sequence of a gene determine size and shape of protein it builds - Example - Sickle cell anemia allele: misshaping of the polypeptide the hemoglobin forms a long inflexible chains, poor at carrying oxygen and clogs vessels Population - A localized group of individuals capable of interbreeding and producing fertile offspring Gene Pool - All the alleles for all loci in a population Three Steps of Evolution - Variation in a trait exists within populations - Traits are heritable (DNA) - Not all alleles are equally passed to the next generation Genetic Drift - Mechanism of evolution purely based on chance - Populations that are small don't always have things happen perfectly - Evolution due to sampling error - Change in allele frequency from random events - Decreases genetic diversity Sexual Selection - Sometimes traits that help with mating, gets you killed more

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Attractiveness of characters, not always survival

Mutation - The original source of variation Gene flow - When populations immigrate or emigrate from an area - Can gain genetic diversity Natural Selection - Adaptations that help with survival - Decreases genetic diversity Lecture 3 Darwin - Evolution as fact and common ancestry - Pattern - Accepted quickly - Pigeon breeding video and seen evolution video - Natural selection drives adaptation - Rejected initially - Principles of natural selection - Variation within a trait - Variation is heritable - Not all individuals reproduce equally/not all offspring survive to reproduce - Natural selection (2) - No known mechanism for the creation of novel variation - No known mechanism for the inheritance of traits - Inheritance - Pangenesis was early explanation for inheritance - Characteristics acquired during the parent's lifetime could be transferred to the offspring - Blending was another idea based on plant breeding - Hereditary material from parents mixes together to form an intermediate trait - DNA DNA

RNA

Base

A,T,C,G

A,U,C,G

Sugar

Deoxyribose

Ribose

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Purines: A,G (longer) Pyrimidines: U,T,C (shorter)

Lecture 4 DNA - Width of dna molecules and hydrogen bonds allow specific bases to pair with each other - C, G have 3 H bonds, A, T have 2 H bonds - Length makes the bonds more difficult to break - Covalent bond - When elements share electrons - When electronegativity the same, no polarity and visa versa Rules of nucleotide polymerization - Anti parallel - DNA and RNA polymerase only add nucleotides to the 3’ end of a strand (5’ to 3’) - Only RNA can begin a newly formed strand, DNA polymerase muse add DNA nucleotides to a preexisting nucleotide (new strand must begin with RNA primers) DNA replication - Lagging strand grows away from fork - Leading strand grows towards fork Mutation - Errors in the DNA replication process - Point mutation - A change in one nucleotide - Often occur during dna replication - Can lead to production of altered protein - Silent mutation - No measurable difference - Nonsense - Affects many amino acids (most negative effect on protein function) - Missense - Conservative: - Non conservative: change of one single amino acid - Insertions and deletions - Additions or loss of nucleotide pairs in a gene - May produce frameshift mutations - RNA is translated by the codon - Duplication - Inversion - Translocation Lecture 5

DNA repair - Main difference between daughter and parental strand is age - DNA is chemically reactive - Proofreading - Done by DNA polymerase - The wrong nucleotide changes the shape of the DNA and is recognized - The nucleotide is cut off and replaced - One strand is damaged - Error is recognized - Area around nucleotide is cut out - DNA polymerase comes back in to fill gap - Mismatch excision repair - Catches errors proofreading did not catch - The mutated dna strand is removed - Gap is repaired by dna polymerase and dna ligase - Base excision repair - Fixes repairs that are not from replication - Remove incorrect base - Endonucleases remove deoxyribose phosphate - Gap is filled with correct base by dna pol and ligase - Nucleotide excision repair - If two T is next to each other, UV can cause them to bond covalently - Distortion is recognized - Helix opened - Endonucleases remove damaged dna strand - Gap is repaired by dna pol and ligase - Double strand repair - End joining - Creates errors - Recognition of broken ends - Exonucleases remove overhang nucleotides - Ligation - What DNA mutates - Some dna mutates more than others - Some mutations are acted on more heavily by natural selection - Gene to protein - Gene expression: the process by which directs protein synthesis involves transcription and translation Lecture 6 Transcription - Rna synthesis is catalyzed by RNA polymerase which pries the DNA strands apart and

hooks together the RNA nucleotides - The Rna is complementary to the DNA template strand - RNA synthesis follows the same base pairing rules as DNA, except that U subs for T - Coding strand is one with promoter, template doesn't have promoter? - Alteration of mrna ends - Each end of a pre mrna molecule is modified in a particular way - The 5’ end receives a modified nucleotide 5’ cap - The 3’ end gets a poly-A tail - These modifications share several functions - They seem to facilitate the export of mrna to the cytoplasm - They protect mrna from hydrolytic enzymes - They help ribosomes attach the 5’ end - Introns are significantly larger than exons - Introns are usually cut out - Ribozymes are catalytic RNA molecules that function as enzymes and can splice RNA Translation - A cell translates an mrna message into protein with the help of trna - Trna transfer mrna into amino acid - Molecules of trna are not identical - Each carries a specific amino acid on the end - Each has an anticodon on the other end; the anticodon base pairs with a complementary codon - Trna molecules consists of a single mrna strand that is about 80 nucleotides long - Accurate translation requires a correct match between a trna and an amino acid, done by the enzyme aminoacyl-trna synthetase and a correct match between trna anticodon and mrna codon - Flexible pairing at the third base is called a wobble and allows trna to bind to more than one codon - Ribosomes facilitate specific coupling of trna anticodons with mrna codons in protein synthesis - The two ribosomal are made of proteins and rrna - Building a polypeptide - Initiation - Elongation - Termination Lecture 7 Gene regulation Lecture 8 Cancer

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A group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body Genomic alterations - Single nucleotide subs - Chromosomal rearrangements - Amplifications and deletions Mutations in somatic cells - Only 5% of cancers are associated with germline mutations Not all tumors are cancerous - Benign tumors results from unregulated cell growth that forms a multicellular mass, removed by surgery - Malignant tumor results from metastasized cells invading other tissues and causing life threatening problems Not all mutations promote tumorigenesis - Driver mutations give growth advantage to tumor cells - Passenger mutations have no direct contribution to cancer phenotype Two fundamental properties - Abnormal cell growth and division - Everything needs to double Mutations - Proto oncogenes: genes whose products promote cell growth and division - Proto oncogenes encode transcription factors that stimulate expression of other genes - Oncogene = proto oncogene mutated - Only one allele of proto needs to mutate or be misexpressed in order to trigger uncontrolled growth - Oncogenes confer dominant cancer phenotype - Tumor suppressor genes - Regulate cell cycle checkpoints and initiate process of apoptosis - Mutated tumor suppressor genes are unable to respond to the checkpoints or undergo apoptosis, usually associated with recessive trait - P53 mutated in over 50% of all cancers - Continuously synthesized at a low rate, present at low levels - Increase conc when damaged dna - Control of apoptosis - Cell halts progress through the cell cycle if dna replication repair or chromosome assembly is aberrant - Mutation of caretaker genes - Cancer cells show higher than normal rates of mutation, chromosomal abnormalities, genomic stability

Lecture 9 Cancer - Oncoviruses - HPV - Contagious cancer - Devil facial tumor disease - Canine transmissible venereal tumor - Contagious cell sarcoma of the syrian hamster - Soft shell clam leukemia - Carcinogens - Any substance that damages dna and causes mutations to occur in proto oncogenes or tumor suppressor genes - Tobacco smoke: most environmental carcinogen - Red meat and animal fat - Alcohol - Tumor grading - PCR - Method of amplifying a specific segment of dna molecule - Relies upon a pair of primers - Short dna molecules that bind to sequences at each end of the sequence to be copied - Used as a starting point for dna replication Lecture 10 Gel electrophoresis - Separates DNA molecules based on size - DNA sample is placed at one end of gel - DNA is negatively charged and goes towards positive charge - Size of dna and… STR - Short tandem repeats are genetic markers used in DNA profiling - Short dna sequences that are repeated many times in a row at the same location - Microsatellites - Current standard for dna profiling is to analyze 13 different str sites Lecture 11 - Open reading frame (ORF) - Part of reading frame that does not have stop codons - A single strand has 3 different reading frames - Predicting gene function - Functional categories of human genes

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Determined by previous function Comparison to known genes and predicted protein sequences from other species Predictions based on annotation and analysis of protein functional domains and motifs

SNP - Single nucleotide polymorphisms - Single base changes in genome - Variations associated with disease condition CNV (copy number variation) - Segments of DNA duplicated or deleted

Linkage and Chromosomal aberrations - Variation in chromosome numbers - Aneuploidy - Occurs during meiosis, sometimes mitosis - When chromosomes or chromatids are supposed to are supposed to disjoin - Down syndrome typically occurs nondisjunction during meiosis, not always...