ABSTRACT
Proteins undergo changes in their amino acid sequences over evolutionary time, as a result of the accumulation of nonsynonymous mutations in their encoding genes. Genes and proteins act as “molecular clocks”, accumulating changes at a relatively constant rate, as mutations occur with a certain probability each time a nucleotide is replicated. From the very beginning of molecular evolution studies, it became apparent that different proteins evolve at very different rates, each evolving according to its own “molecular clock”. For instance, in their early studies Zuckerkandl and Pauling (1965) already noted that the high rate of evolution of hemoglobin was “spectacularly
at variance” with the high degree of conservation of cytochrome c. The subsequent accumulation of molecular data for other proteins revealed a huge diversity in proteins’ rates of evolution. For instance, using DNA sequence data from 36 genes in different mammalian species, Li et al. (1985) observed that the gene encoding interferon γ had accumulated nonsynonymous mutations at a rate that was ~700-fold higher than that for the gene encoding histone H4. The current availability of the complete genomes of multiple organisms now allows us to study proteins’ rates of evolution at an unprecedented scale. If we take any two genomes (e.g., those of human and mouse), and compare the proteins encoded by each pair of orthologous genes, some proteins will be very similar (or even identical) in both organisms, whereas others will exhibit several amino acid differences (see Figure 7.1), in spite of the fact that all pairs of orthologs diverged over the same amount of time (i.e., the time elapsed since the divergence of the two compared species).
