It has not escaped our notice that the specific paring we have postulated immediately suggest a possible copying mechanism for the genetic material

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1 5-carbon sugar hosphate functional group Nitrogenous base 2 types urines = 2 rings 5 & 6 member N containing ring yrimidines = 1 ring 6 member N containing ring Geometry and space requires complimentary base pairing It has not escaped our notice that the specific paring we have postulated immediately suggest a possible copying mechanism for the genetic material DNA synthesis reaction end of strand CH 2 O Base CH 2 O Base CH 2 O Base CH 2 O Base OH CH 2 O Synthesis reaction Base CH 2 O H Base OH OH end of strand 1

2 Completely single stranded G A A T C T G C olymerase inactive Completely double stranded G A A T C T G C olymerase inactive C T T A G A C G Single strand as template plus end to start synthesis G A A T C T G C olymerase active C T T OH Characteristics of replication : Newly synthesized leading strand RNA primer DNA polymerase III Formation of the leading strand Replication fork 2

3 Formation of lagging strand Lagging strands RNA primers DNA polymerase III Okazaki fragments Gap DNA polymerase III beginning synthesis of new fragment Topoisomerase nicks DNA to relieve tension from unwinding 3 DNA olymerase III synthesizes leading strand 1 Helicase opens helix 4 rimase synthesizes RNA primer DNA olymerase III elongates primer; produces Okazaki fragment 5 DNA olymerase I excises RNA primer; 6 fills gap DNA ligase links Okazaki fragments to form continuous strand A A C T G G C Wild type T T G A C C G A A C T G G C A A C T A G C MUTANT T T G A T C G T T G A T C G A A C T G G C DNA replication DNA replication T T G A C C G A A C T G G C A A C T G G C arental DNA Wild type T T G A C C G T T G A C C G First generation progeny A A C T G G C Wild type T T G A C C G Second generation progeny 3

4 DNA point mutation can lead to a different amino acid sequence. DNA CAC sequence GTG Amino acid sequence DNA CAC sequence GTG Amino acid sequence GTG CAC GTG CAC GAC CTG GAC CTG TGA ACT TGA ACT GGA CCT Valine Histidine Leucine Threonine roline Valine Start of coding sequence Histidine Leucine Threonine GGA CCT roline CTC GAG Glutamic acid CAC GTG Valine CTC GAG Glutamic acid CTC GAG Normal Mutant Glutamic acid henotype Normal red blood cells Sickled red blood cells Sickle cell anemia reduces the ability of blood to flow through vessels as they produce clogs. Sickle cell anemia is not equally represented across races 4

5 rovides protection from malaria Endemic falciparum malaria ercent of population with sickle-cell allele (Hemoglobin S) Mutation and DNA Repair Mechanisms DNA Repair Mechanisms Mutation and DNA Repair Mechanisms DNA Repair Mechanisms 5

6 Mismatched bases. T G T C C A T C G C A C A G G G OH olymerase I can repair mismatches. T G T C C A T C G C A C A G G T OH G OH Redundancy First base U UUU henylalanine UUC UUA UUG Leucine C CUU CUC Leucine CUA CUG GUU G GUC GUA GUG Valine UCU UCC UCA UCG CCU CCC CCA CCG GCU GCC GCA GCG Second base U C A G UAU Serine UAC UAA UAG CAU Histidine CGU roline CAC CGC CAA CGA Glutamine CAG CGG GAU Alanine GAC GAA GAG UGU Tyrosine UGC Stop codon Stop codon UGA UGG AUU ACU AAU AGU AUC Isoleucine ACC Asparagine A AAC AGC Theronine AUA ACA AAA AGA AUG Methionine ACG Lysine AAG AGG start codon Aspartic GGU acid GGC GGA Glutamic GGG acid Cysteine Stop codon Tryptophan Arginine Serine Arginine Glycine U C A G U C A G U C A G U C A G Third base 64 different codons can be created but there are only 20 exist Why does most redundancy occurs in the third position ACU Threonine CCU roline GCU Alanine UCU Serine UCC Serine UCA Serine UCG Serine UGU Cysteine UAU Tryosine UUU henylalanine AGU & AGC Serine 6

7 oint urines A yrimidines C DNA polymerase makes mistakes during synthesis or ironically, in repair. Transition G Transversion T oint Transitions out number transversions approximately 2:1 WHY??? Why does sequence difference asymptote? oint 7

8 oint Silent Mutation oint Frameshifts 8

9 oint Nonsense oint Missense 9

10 Red fox (Vulpes vulpes) Mink (Mustela vision) Single gene mutations can produce multiple phenotypes C. elegans Control Natural selection active Experimental Natural selection inactive E. coli Inserted large mutation Measured cell growth What % retained insertion? Gene duplication 10

11 Hemoglobin Most well understood case of gene duplication Alpha and beta subunits binding hemes % of total globin synthesis ε Gγ Birth α-like family α, α 2, ζ α β β-like family β, ε, δ, Gγ, Aγ ζ Aγ High sequence similarity between hemoglobin genes All globin genes have evolved by a series of duplications, rearrangements and mutations from a single ancestral globin gene. α gene family α1 α2 ξ β gene family ε Gγ Aγ δ β Myoglobin 11

12 = genome duplication = Hexaploid 12

13 Jumping Genes - Transposable elements Specific regions of DNA are excised and inserted 13

14 Canterbury Tales Whan that Ap rylle / wyth hys showres soote the drowhte of Marche / hath pcede to the rote Whan that Auerell w t his shoures soote the droght of Marche hath pced to the roote Whan that Ap rille with his showres soote the drowhte of marche hath pced to the roote Whan that Aueryll w t his shoures soote the droghte of March / hath pced to the roote Christ Church Egerton British Library Egerton Hengwrt British Library Hengwrt Christ Church Canterbury Tales Whan that Ap rylle / wyth hys showres soote the drowhte of Marche / hath pcede to the rote Whan that Auerell w t his shoures soote the droght of Marche hath pced to the roote Whan that Ap rille with his showres soote the drowhte of marche hath pced to the roote Whan that Aueryll w t his shoures soote the droghte of March / hath pced to the roote Christ Church Egerton Hengwrt British Library 14