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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