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PHYS 4xx Intro 3 1 PHYS 4xx Intro 3 - DNA composition and structure Composition and structure • sugar, phosphate, base combination is called a nucleotide • nucleotides polymerize to form DNA and RNA, through a linkage between a sugar from one nucleotide and a phosphate from another RNA: adenine, guanine, cytosine, uracil DNA: adenine, guanine, cytosine, thymine • in double-stranded DNA, the bases lie in the interior of the helix, and hold it together through hydrogen bonding between base pairs: one purine and one pyrimidine: adanine/thymine and guanine/cytosine. 5' O- H sugar base O H2C PO4 O H H PO4 sugar H O OH -O P O PO4 H sugar H H OH OH Species bacteriophage φX174 HIV type 2 mycoplasma genitalium mycoplasma pneumonia E. coli Homo sapiens amphibians plants • • • PO4 O H2C H sugar base O 3' 3' 5' -O P O 5' 3' genome size (106 bp) 0.005386 0.009671 0.58 0.82 4.7 3,000 up to 80,000 wide range, up to 900,000 genes 9 473 716 4100 ~30,000 length (µm) 197 282 1600 1.0 metres 27 km typical protein has 300-400 AA, corresponding to ~1000 bp of DNA from above, DNA in the smallest cells is almost entirely coding human DNA is 99% non-coding © 2010 by David Boal, Simon Fraser University. All rights reserved; further copying or resale is strictly prohibited. PHYS 4xx Intro 3 2 Microscopic geometry of DNA So far, we have just considered the general structure of DNA as a helix with the bases facing into the interior of the helix. A more detailed picture would examine the orientation of the bases, which are small planar organic rings. One needs several variables to describe these orientations, both within a base pair, and between successive base pairs: twist propeller twist (between bases in a pair) twist, T roll, R slide, S The average value of twist is approximately 32o, which corresponds to 360 / 32 = 11.3 base pairs per complete turn. But there is variation, with 36o for -AAAAAA-TTTTTT- roll Examples (Calledine and Drew, Fig. 3.12): scatter plot of data from X-ray studies AA/TT steps are rigid +20 o -AA-TT- 0o -10 o -3 Å slide +3 Å © 2010 by David Boal, Simon Fraser University. All rights reserved; further copying or resale is strictly prohibited. PHYS 4xx Intro 3 3 roll GG/CC steps are bimodal +20 o -GG-CC- 0o -10 o -3 Å slide +3 Å Length • 0.34 nm per base pair: at 3 x 109 bp, human DNA has a contour length of 1.02 m • random coil has a much smaller dimension, ξp = 53 nm for helix • in eukaryotic cells, DNA is wound around histones to aid in packaging Supercoiling • when subject to a torsional stress, DNA may form supercoils like a telephone cord (demo) • geometry of coil is described by twist and writhe Protein synthesis Genetic information is stored in the DNA sequences using the GCAT alphabet. Both the sequence for a gene, and it's complement (ie, CGTA) is stored, although other information is also encoded to indicate which is the correct direction for transcription. The sequence on the DNA master blueprint corresponding to a specific protein is transcribed onto a string of messenger RNA or mRNA, written in the GCAU alphabet. It is the mRNA sequence that is called the sequence for the protein. The mRNA is then read to create the amino acid sequence. There are 20 commonly used amino acids. Each one of these can be attached to a short string of RNA called tRNA (t for transfer), about 70-90 nucleotides long. At one end of the tRNA is an attachment site for an amino acid, further along the string is a series of three nucleotides which are the anticodon for the AA, complementary to the codon carried by the mRNA. © 2010 by David Boal, Simon Fraser University. All rights reserved; further copying or resale is strictly prohibited. PHYS 4xx Intro 3 4 Folded, tRNA looks like an L, but somewhat unfolded, it appears like a cloverleaf: 3' attachment site for amino acid anticodon At 3 nucleotides per codon, there are 43 = 64 unique codes for amino acids - far more than 20. Thus: • some AAs can be carried by more than one tRNA • a given tRNA may be able to fit into several different slots on the mRNA, if it is primarily sensitive to the first two nucleotides in the three-letter codon. Ala Arg Asp Asn Cys Glu Gln Gly His Ile Leu Lys Met Phe Pro Ser Thr Trp Tyr Val GCA AGA GAC AAC UGC GAA CAA GGA CAC AUA UUA AAA AUG UUC CCA AGC ACA UGG UAC GUA GCC AGG GAU AAU UGU GAG CAG GGC CAU AUC UUG AAG GCG GCU CGA CGC CGG CGU start stop AUG (met) UAA UAG UGA GGG GGU AUU CUA CUC CUG CUU UUU CCC CCG CCU AGU UCA UCC UCG UCU ACC ACG ACU UAU GUC GUG GUU © 2010 by David Boal, Simon Fraser University. All rights reserved; further copying or resale is strictly prohibited.