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Biochemistry: DNA Research History


1890 Meischer investigated salmon sperm because genetic material must be in reproductive cells. He gave a salmon a squeeze, collected the stuff, and assessed the components. He found that salmon sperm contain proteins, lipids, and something acidic that he named nucleic acids. The name stuck. At the time they thought heritable information was stored in proteins--that proteins were the genetic material.

1944 Avery, McCarty & McLeod took apart bacteria and injected the DNA from a "rough" pneumococcus into the "smooth" one -- and it became "rough". They transformed nonpathogenic bacteria to pathogenic by inserting DNA.

1952 Hershey & Chase sorted out what happens with P (phosphate) and S (sulfur) in DNA. Amino acids cysteine and thionine contain S but not P. DNA contains P but not S. H&C labelled a virus with both P and S, then tracked the path of the elements through the generations. They ascertained that proteins are NOT the genetic material.

1952 Crick, Watson, Franklin & Wilkins determined the physical structure of DNA. Franklin was the only woman on the team, and did the dirty work of the radiography. She got cancer and died, and didn't get a Nobel prize with the rest of them because they don't give the Prize to dead people. Crick thinks that a small dose of LSD helped him think up the spiral staircase structure.

1958 Meselson & Stahl demonstrated semiconservative replication by labelling DNA with heavy nitrogen (N15), and tracking the progress of the N through the generations. In each generation 1/2 of the old N15 was present, along with 1/2 regular N14. The method they used was gradient centrifugation with cesium chloride (CsCl). Cesium is heavy, chloride is light.

Chargaff's rule: in the genetic material the A:T ratio and G:C ratio are both 1:1.

Humans have approximately 50,000 transcribable genes. The DNA code is nearly universal. The organisms whose codes differ the most are thought to have split off earlier in evolution. Archaea and extremophiles have the most different DNA. The code is redundant (only 20 amino acids) and degenerate.

degenerate = in many cases the third position in a codon doesn't matter.

ATG codes to start transcription and results in a methionine as the leader on the protein

TAA, TAG, TGA are stop codons, notice the degeneracy.

substitution = a point mutation

active substitution = causes protein mutation and possibly lethal termination of transcription

silent substitution (esp in the 3rd position) = can cause no change in the amino acid sequence

frame shift = adding or removing a base from the sequence can cause a perfectly good gene to become gibberish by totally altering the amino acid sequence. Often lethal.

FACTOIDS:

from the 1' to 1' carbons in nucleotides, the A-T and C-G distance is 1.08 nm

DNA is hydrophilic on the outside, hydrophobic on the inside of the spiral

the base pairs stack close enough to allow Van der Waals interactions

there are 10 base pairs per turn, or each base pair rotates the polymer 36 degrees on the spiral's axis

full turn rise = 3.4 nm

DNA has a major and minor groove

the DNA spiral is right handed---as if you were going up a spiral stair and the rail would be in your right hand

the B form of DNA is most common and is the minimum energy structure and fully hydrated. Two other forms exist

DNA's A form is found in old bone fragments, and has lost its water of hydration. The spiral packs just a little bit tighter.

the Z form is a left hand spiral with a zigzag shape that is not found in nature, only synthesized (this is demonic)

template strand = noncoding strand of DNA, mRNA complement forms on this strand

coding = nontemplate strand has the same pattern as the RNA (except T vs U)

rough endoplasmic reticulum = where the ribosomes are

tRNA = has anticodon loop and brings aa's to the ribosome games

anticodon loop = three bases that match mRNA

acyl site = place in ribosome where tRNA with AA affixes

peptidal site = where the peptide chain grows

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