Transcript Document

An Austrian chemist
Studied chemistry in
Vienna University,
Yale University
He worked at the
University of Berlin
A professor at the
Columbia University
First Parity Rule
Second Parity Rule
GC Rule
Cluster Rule
What we can understand
How double-stranded DNA became an intracellular
alarm signal
How potentially recombining nucleic acids can
distinguish between "self" and "not-self" so leading
to the origin of species
How isochores evolved to facilitate gene replication
How unlikely it is that any mutation can ever
remain truly neutral
A. Chargaff used quantitative chromatography to separate
DNA bases
(1) Purines
(adenine & guanine)
(2) Pyrimidines (cytosine & thymine)
B. Looked at DNA from many different species
C. Looked at DNA from different individuals within species
D. Chargaff's basic observations, stated as Chargaff's Rules:
(1) Individuals within species had same % of 4 bases
(a) % Didn't vary with tissue, age, nutrition or environment
(2) Different species had different % of 4 bases
(3) Closely related species had similar % of 4 bases
(4) Also noted that %A = %T and %C = %G
% of A = % of T
% of C = % of G
Sum of A+G (purines) =
Sum of C+T (pyrimidines)
% of C+G ≠ % of A+T in the
DNA
Less well known is the fact that Chargaff's rules apply
approximately and separately to each of the two strands
of dsDNA
Aw=Tc , Tw=Ac , Cc= Gw , Gc=Cw
(where the letters represent the molar fraction of a
base on one strand)
Ac ≈ Tc , Aw ≈ Tw , Cc ≈ Gc , Cw ≈ Gw
Complementary strands are approximately symmetric
in nucleotide content. If they are true
Aw=Ac , Tw=Tc , Cw=Cc , Gw= Gc
Equality — even in the separated DNA strands — of 6amino [A + C] and 6-keto [G + T] nucleotides, in the
absence of all other pairing regularities
Departures from strand symmetry or Chargaff asymmetries
can be expressed by differences:
(A-T)/(A+T) and (C-G)/(C+G) for each strand
Strand symmetry originates from identical
mutation/substitution processes affecting each strand
For example
same probability of changing
Ac
Tc and Aw
Tw
However, some mutation processes are known to be strand
asymmetric. Furthermore, nucleotide substitution is subjected
to selection which may depend on information contained in
only one strand.
The ratio of C + G to the total bases (A+C+G+T) tends to
be constant in a particular species
But varies between species
DNA base composition is a reflection of phylogenetic
relationship
It is evident that those strains which mate with one
another (i.e. strains within the same 'variety') have similar
base compositions
Thus strains of variety 1 ..., which are freely intercrossed,
have similar mean GC content
The organismal phenotype comprises two components
the classical phenotype, corresponding to the 'gene products
the genome phenotype which is defined by [base]
compositional constraints
Erwin Chargaff provides more evidence that DNA = genetic
material
Analysis of base composition of DNA compared between different
organisms
Nitrogenous bases
Adenine
(A)
Thymine
(T)
Guanine
(G)
Cytosine
(C)
Conclusions of Chargaff
DNA composition is species specific
The amounts of A,G,C and T are not the same between species
Ratios of nitrogenous bases vary between species
Fourth observation was critical to Watson and Crick as they
deduced the structure of DNA