Welcome to BMB 400TextRequired work and pointsGrading PolicyMake-up Exam PoliciesAcademic Integrity PolicyFundamental properties of genesWhat are genes?Characteristics of GenesTypes of allelesMendel’s 1st Law: Alleles segregate equallyMendel’s 2nd Law: Different genes assort independentlyBehavior of alleles mimics movement of chromosomes during meiosisMeiosis IMeiosis I (continued)Linked genes lie along chromosomes in a linear arrayExpectation for unlinked genes in a backcrossLinkage causes deviations from 2nd LawSlide 20ComplementationMutations in different genes complementUse of complementation analysis in deducing number of genes in a pathwayGrowth factor requirementsComplementation restores prototrophySlide 32How genes encode proteinsRecombination within genes allows construction of a gene mapConclusions from recombination mapping of rII“One gene encodes one polypeptide”The gene and its polypeptide product are colinearCharacteristics of codons3. Effect of frameshift mutations rule out a punctuated codeRestoration of function by indels of 3n nucleotides show that the code is read in triplets from a fixed starting pointCentral Dogma of Molecular BiologyOnly one strand of duplex DNA codes for a productUntranslated sequences are at the ends of mRNARegulatory signals are parts of genesFinding the function of genes• “Molecular Biology of Genes and Genomes”• Biochemical basis for genetic phenomena:• structure of genes and chromosomes• replication and maintenance of DNA• pathway of gene expression• regulation of gene expression • Instructor: Ross HardisonTA: Cathy VrentasWelcome to BMB 400• Customized textbook, 2 volumes•Text (built from lecture notes)•Problems•Answers• You can supplement it with other texts for broader coverageE.g. Lewin’s Genes VIITextRequired work and points•4 scheduled EXAMS–Midterm 1: 80 points–Midterm 2: 80 points–Midterm 3: 80 points–Final exam: 160 points•Required project report–100 points•Total points for required material:–500 pointsGrading Policy•Point cut-offs for letter grade assignments determined by distribution of the sums of the scores on the required material (4 exams + project report)•In addition, you will have extra credit opportunities–About 4-5 unannounced “quizzes”, which are more like in-class exercises. Total about 20-25 pts–Additional projects to explore Internet-based resources and servers in biochemistry, molecular genetics and genomics•E.g. cut-off for A may be 400, you have 380 for exams+project, and 30 points for extra credit. Your 410 total points gets an A.Make-up Exam Policies•Make-ups for EXAMS –can be scheduled for students who must miss the exam for an acceptable excuse•E.g. illness, death in the immediate family.–will be problem-solving/essay–may be written or oral at the discretion of the instructor.•No make-ups will be offered for any “quizzes”Academic Integrity Policy•Academic integrity is the pursuit of scholarly activity free from fraud and deception. •Dishonesty includes, but is not limited to, cheating, plagiarizing, facilitating acts of academic dishonesty by others, submitting work of another person, or tampering with the academic work of other students. •Cite the source for any material or ideas obtained from others. •All exam answers must be your own, and you must not provide any assistance to other students during exams. •Academic dishonesty can result in assignment of "F" by the course instructors or "XF" by Judicial Affairs as the final grade for the student.Fundamental properties of genes•Genes are heritable units, arranged linearly along chromosomes.•Complementation analysis of a large number of mutants defines genes that determine a function.–E.g., biosynthetic pathway or DNA replication.•Genetic techniques in microorganisms were used to determine the fine structure of a gene.•Genes encode polypeptides–Codons are triplets of nucleotides that encode an amino acid.What are genes?Characteristics of Genes•Determine heritable phenotypes•Are mutable: allelic variants•Units of heredity •Are on chromosomes–Behavior of genes mimics movement of chromosomes–Allelic variants segregate equally (1st Law)–Different genes usually sort independently (Mendel’s 2nd Law) •Linked on chromosomes in a linear arrayTypes of alleles•Wild type: normal, functional product•Loss-of-function: usually recessive–Null: No product–Hypomorph: Less product•Gain-of-function: usually dominant–New function–Hypermorph: More product•Dominant negative: mutant product interferes with function of wild-type product•Some alleleic variants have no observable effectsyyYYyyYYgreenyellowyellowParentsGametesYyHybrid F1 generationYyYyYyMale gametesFemale gametesyyYYyYYyF2 generationYY : 2Yy : yyObtain a ratioof 3:1 dominant to recessive phenotypesyellowgreenMendel’s 1st Law: Alleles segregate equallyGenes behaveas units: Discrete phenotypesRRYYrryyyround yellowwrinkled greenRYryParentsGametesF1 generationRrYyRrYyRYRyrYryGametesRYRyrYryRRYYRRYyRrYYRrYyRRyYRRyyRryYRryyrRYYrRYyrrYYrrYyrRyYrRyyrryYrryyGametesF2 generationThe F2 generation produces:9331:::Parentalphenotype roundyellowroundgreenwrinkledyellowwrinkledgreenRecombinant phenotypesParental phenotypeMendel’s 2nd Law: Different genes assort independentlyR does not stay with Y.r does not stay with y.Get nonparental phenotypes.Behavior of alleles mimics movement of chromosomes during meiosis•Alleles correlate with homologous pairs of chromosomes•Equal segregation of alleles: separation of homologous chromosomes at anaphase I of meiosis•Independent assortment of different genes: independent separation of homologs of different chromosomes during meiosis•Chromosomal theory of inheritance (Sutton and Boveri)Meiosis IMeiosis I (continued)1st Law: R goes to precursor to 1 germ cell, r goes to another.2nd Law: R can assort with y or Y.Linked genes lie along chromosomes in a linear array•Number of genes > number of chromosomes•Some pairs of genes show substantial deviation from the predictions of Mendel’s 2nd Law.•Propensity of two genes to stay together rather than assorting independently is linkage.–Most easily seen in a backcross between an F1 heterozygote and a recessive homozygote.•Genes on the same chromosome can be separated by recombination between homologous chromosomes.–Chiasmata formed between chromosomes in meiosis•Recombination maps