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A new method is suggested here for determining the amino acid sequence of proteins from the mass spectrum of a single solution. A computer simulation of the reconstruction of the sequence from ideal mass-spectrometer data is presented. The method requires first the random fragmentation of a protein, as by partial acid hydrolysis. Volatile derivatives of the fragments, still mixed together, must next be made. The mass measurements are performed on the mixture of volatile derivatives. All the required chemical treatments would be simple and of such nature that the whole analysis, beginning with a sample of purified protein and ending with the computer printout of the amino acid sequences, could be made rapidly. The required amount of volatile derivative protein sample is expected to be very small, of the order of 1 mg. This should make feasible various experiments, for example with single organisms which are impossible at present.

The triplets of nucleotides which apparently specify the detailed structure of proteins fall into a regular pattern: the 64 combinations of four nucleotides taken three at a time, are resolved into 32 pairs. The second member of each pair is identical with the first, except that in one position a purine is replaced by the other purine or a pyrimidine by the other pyrimidine. Almost all of the reported triplets fit into this pattern, and from it one can predict which amino acids will be found to correspond to the remaining 19 unidentified triplets. This pattern accounts for several of the observations concerning regularities in the data, partially determines the order of the nucleotides in each triplet, and suggests a structural basis for transfer RNA specificity.

Some complications of the “overlapping” hypothesis of nucleic acidprotein coding are discussed, and a procedure outlined for elucidating such a code, using a minimum of assumptions concerning its detailed structure. Using only data from published protein sequences, a non-overlapping code would be unsolvable. An overlapping code would, however, impose constraints on adjacent linkages, such that not all mathematically possible sequences could be produced. There are a large number of ways in which the known sequence data can be organized so as to develop patterns which would be non-random if such constraints occur. Finally, if these results are positive, given enough original data, it should be possible to use such patterns to predict the sequences which are missing from the data, but consistent with it. From these, a detailed formulation of the code should eventually be possible. The first result of this approach shows that the reported “alleles” do not occur at random; certain pairs occur with greater than chance frequency. This may be interpreted as a “constraint” imposed by the context of the adjacent links.

The structure of present-day ferredoxin, with its simple, inorganic active site and its functions basic to photon-energy utilization, suggests the incorporation of its prototype into metabolism very early during biochemical evolution, even before complex proteins and the complete modern genetic code existed. The information in the amino acid sequence of ferredoxin enables us to propose a detailed reconstruction of its evolutionary history. Ferredoxin has evolved by doubling a shorter protein, which may have contained only eight of the simplest amino acids. This shorter ancestor in turn developed from a repeating sequence of the amino acids alanine, aspartic acid or proline, serine, and glycine. We explain the persistence of living relics of this primordial structure by invoking a conservative principle in evolutionary biochemistry: The processes of natural selection severely inhibit any change a well-adapted system on which several other essential components depend.

Because of the high temperatures prevailing in the lower atmosphere of Venus, its chemistry is dominated by the tendency toward thermodynamic equilibrium. From the atomic composition deduced spectroscopically, the thermodynamic equilibrium composition of the atmosphere of Venus is computed, and the following conclusions drawn. (i) There can be no free carbon, hydrocarbons, formaldehyde, or any other organic molecule present in more than trace amounts. (ii) The original atomic composition of the atmosphere must have included much larger quantities of hydrogen and a carbon/oxygen ratio/= 0.5. (This ratio is now almost precisely 0.5.) (iii) The present atomic proportions of the atmosphere of Venus are so unique that an evolutionary mechanism involving two independent processes seems necessary, as follows. Water, originally present in large quantities, has been photodissociated in the upper atmosphere, and the resulting atomic hydrogen has been lost in space. The resulting excess oxygen has been very effectively bound to the surface materials. (iv) There must be some weathering process, for example, violent wind erosion, to disturb and expose a sufficient quantity of reduced surface material to react with the oxygen produced by photodissociation.

Thermodynamic equilibrium composition calculations on carbon, hydrogen, oxygen, and nitrogen in Earth, Venus, Mars, and Jupiter atmospheres