Protein evolution within and between species.

Protein evolution can be seen as the successive replacement of amino acids by other amino acids. In general, it is a very slow process which is triggered by point mutations in the nucleotide sequence. These mutations can transform into single nucleotide polymorphisms (SNPs) within populations and diverging proteins between species. It is well known that in many cases amino acids can be replaced by others without impeding the functioning of the protein, even if these are of quite different physico-chemical character. In some cases, however, almost any replacement would result in a functionally deficient protein. Based upon comprehensive published SNP data and applying correlation analysis we quantified the two antagonist factors controlling the process of amino acid replacement and thus protein evolution: First, the degenerate structure of the genetic code which facilitates the exchange of certain amino acids and, second, the physico-chemical forces which limit the range of possible exchanges to maintain a functional protein. We found that the observed frequencies of amino acid exchanges within species are best explained by the genetic code and that the conservation of physico-chemical properties plays a subordinate role, but has nevertheless to be considered as a key factor. Between moderately diverged species genetic code and physico-chemical properties exert comparable influence on amino acid exchanges. We furthermore studied amino acid exchanges in more detail for six species (four mammals, one bird, and one insect) and found that the profiles are highly correlated across all examined species despite their large evolutionary divergence of up to 800 million years. The species specific exchange profiles are also correlated to the exchange profile observed between different species. The currently available huge body of SNP data allows to characterize the role of two major shaping forces of protein evolution more quantitatively than before.