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The Molecular Basis of Inheritance (((((((((Viral DNA Can Program Cells,…

- - - - Viral DNA Can Program Cells
        
        evidence that DNA was the genetic material came from studies of viruses that infect bacteria
        these viruses are called bacteriophages (meaning "bacteria-eaters") or phages for short
        viruses are simpler than cells; there is a little more DNA (or sometimes RNA) enclosed by a protective coat, which is often just protein
        to be able to produce more viruses, a virus must infect a cell and then take over the cell's metabolic machinery
        
        in 1952, Alfred Hershey and Martha Chase performed experiments showing that DNA is the genetic material of a phage known as T2
        this is one of the many phages that infect E. coli, which is a bacterium that normally lives in the intestines of mammals and is a model organism for molecular biologists
        T2 is made up almost entirely of DNA and protein and could quickly turn E. coli cells into T2-producing factories that released new copies of the phages when the cell ruptured
        T2 could reprogram its host cell to produce viruses
        T2 actually enters the E. coli during infection.
        
        DNA Can Transform Bacteria
        
        in 1928, medical officer Frederick Griffith was trying to develop a vaccine against pneumonia by studying Streptococcus pneumoniae, a bacterium that causes pneumonia in mammals
        he had 2 strains of the bacterium, one pathogenic and one nonpathogenic
        he found that when he killed the pathogenic bacteria with heat and then mixed the cell remains with living bacteria of the nonpathogenic strain, some of the living cells became pathogenic
        the newly acquired pathogenicity was inherited by all the descendants of the transformed bacteria
        
        apparently some chemical component of the dead pathogenic cells cause this heritable change, but they didn't know why
        Griffith called the phenomenon transformation, that is now defined as a change in genotype and phenotype due to the assimilation of external DNA by a cell
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        Base Pairing to a Template Strand
        
        the linear sequence of nucleotides can be determined by referring to the uncovered strand and applying the base-pairing rules
        the two strands are complementary; each stores the information necessary to reconstruct the other
        when a cell copies a DNA molecule, each strand serves as a template for ordering nucleotides into a new, complementary strand
        nucleotides line up along the template strand according to the base-pairing rules and are linked to form the new strands
        a conservative model is where there was one double-stranded DNA molecule at the beginning of the process, there are soon two, each an exact replica of the "parental" molecule
        
        semiconservative model can be distinguished from a conservative model of a replication, in which the two parental strands somehow come back together after the process
        in a dispersive model, all four strands of DNA following replication have a mixture of old and new DNA
      - Structure of DNA
      - Rosalind Franklin developed an X-ray diffraction image of DNA
        her images were captured by X-rays that were deflected (diffracted) as they passed through aligned fibers of purified DNA
        her photo proved that DNA was helical in shape
        it also helped to see the nitrogenous bases in the DNA
      - the presence of two strands is now what we call the term double helix
        in the picture above, the two sugar-phosphate backbones are antiparallel - that is their subunits run in opposite directions
        the side ropes represent the sugar-phosphate backbones, and the rungs represent pairs of nitrogenous bases
        imagine twisting the ladder to form a helix
        the helix makes one full tern every 3.4 nm along its length; bases are stacked just 0.34nm apart, there are ten layers of base pairs (rungs) of the ladder, in each full turn of the helix
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        Antiparallel Elongation
        
        each strand of DNA (either strand of the double helix) is like a one way street
        the two strands of DNA in a double helix are also antiparallel, meaning that they are oriented in opposite directions to each other (like a regular two-way street)
        the two new strands must also be antiparallel to their template strands when formed during DNA replication
        
        DNA POLYMERASES CAN ADD NUCLEOTIDES ONLY TO THE FREE 3' END OF A PRIMER/GROWING DNA STRAND, NEVER TO THE 5' END
        
        leading strand - DNA polymerase elongating the new DNA in the mandatory 5' -> 3' direction
        lagging strand - DNA pol III working along the other template strand in the direction away from the replication fork
        
        the lagging strand is synthesized discontinuously, as a series of fragments. these fragments are called Okazaki fragments
        
        Synthesizing a New DNA Strand
        
        the previously unwound sections of the parental DNA are going to serve as the templates for the synthesis of new DNA strands
        however, enzymes that synthesize DNA cannot initiate the synthesis of a polynucleotide -- they can only add DNA nucleotides to the end of an already existing chain that is base-paired with the template strand
        initial nucleotide chain is produced during DNA synthesis is actually a short stretch of RNA
        this RNA ^ above is called a primer and is synthesized by the enzyme primase
        primase then starts a complementary RNA chain with a single RNA nucleotide and adds RNA nucleotides one at a time (using the parental DNA strands as a template)
        the completed primer is usually 5-10 nucleotides long and is base-paired to the template strand
        the new DNA strand will start from the 3' end of the RNA primer
        
        enzymes called DNA polymerases catalyze the synthesis of new DNA by adding nucleotides to the 3' end of a chain
        most DNA polymerases require a primer and a DNA template strand, along which complementary DNA nucleotides are lined up
        each nucleotide to be added to a growing DNA strand consists of a sugar attached to a base and to three phosphate groups
- - - - proteins called histones are responsible for the first level of DNA packing in chromatin
        each histone contains about 100 amino acids - the total mass of histone in chromatin roughly equals the mass of DNA
        four types of histones are most common in chromatin
        
        Exploring Chromatin Packing in Eukaryotic Chromosome
        
        in electron micrographs, unfolded chromatin is 10 nm in diameter (such chromatin resembles beads on a string)
        each "bead" is a nucleosome, the basic unit of DNA packing; the "string" between the beads is called linker DNA
        
        a nucleosome consists of DNA wound 2 times around a protein core of eight histones, two each of the main histone types
        
        What exactly is chromatin?
        
        chromatin is the complex of DNA and protein in a eukaryotic cell
        
        Replicating the Ends of DNA Molecules
        
        for linear DNA, the usual replication machinery cannot complete the 5' ends of daughter DNA strands
        ^ this is another consequence of the fact that a DNA polymerase can add nucleotides only to the 3' end of a preexisting polynucleotide
        most prokaryotes have a circular chromosome, with no ends, so the shortening of the DNA does not occur
        eukaryotic chromosomal DNA molecules have special nucleotide sequences called telomeres at their ends
        telomeres do NOT have genes, instead, the DNA typically consists of multiple repetitions of one short nucleotide sequence
        
        telomeres have two protective functions:
        
        specific proteins associated with telomeric DNA prevent the staggered ends of the daughter molecule from activating the cell's systems for monitoring DNA damage
        
        telomeric DNA acts as a kind of buffer zone that provides some protection against the organim's genes shortening, somewhat how aglets on a shoelace slow down its unraveling
        
        TELOMERES DO NOT PREVENT THE EROSION OF GENES NEAR THE ENDS OF CHROMOSOMES; THEY MERELY POSTPONE IT
        
        Proofreading cont.
        
        an important function of the DNA repair enzymes in our skin cells is to repair genetic damage caused by the ultraviolet rays of sunlight
        mutations can change the phenotype of an organism
        and if they occur in germ cells, mutations can be passed on from generation to generation
        the vast majority of such changes either have no effect or are harmful, but a very small percentage can be beneficial
        
        ultimately this process leads of the new species and thus to the rich diversity of life on Earth today