Tendency for local repetitiveness in amino acid usages in modern proteins.
Systematic analyses of human proteins show that neural and immune system-specific, and therefore, relatively "modern" proteins have a tendency for repetitive use of amino acids at a local scale ( approximately 1-20 residues), while ancient proteins (human homologues of Escherichia coli proteins) do not. Those protein subsegments which are unique based on homology search account for the repetitiveness. Simulation shows that such repetitiveness can be maintained by frequent duplication on a very short scale (one to two codons) in the presence of substitutive point mutation, while the latter tends to mitigate the repetitiveness. DNA analyses also show the presence of cryptic (i.e. "out of the codon frame") repetitiveness, which cannot fully be explained by features in protein sequences. Simulative modification of the amino acid sequences of immune system-specific proteins estimate that 2.4 duplication events occur during the period equivalent to ten events of substitution mutation. It is also suggested that the repetitiveness leads to longitudinal unevenness within a given peptide domain. Those peptide motifs which contain similarly charged residues are likely to be generated more frequently in the presence of the tendency for repetitiveness than in its absence. Therefore, the neutral propensity of DNA for duplication, which can also tend to generate repetitiveness in amino acid sequences, seems to be manifested primarily when the constraints on amino acid sequences are relatively weak, and yet may be positively contributing to generation of unevenness in modern proteins.
Nishizawa
K
K
Department of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi, Tokyo, 173, Japan. kazunet@med.teikyo-u.ac.jp
Nishizawa
M
M
Kim
K S
KS
D000465:Algorithms; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003198:Computer Simulation; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D020440:Gene Duplication; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017354:Point Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid; D012091:Repetitive Sequences, Nucleic Acid
D018076:DNA, Complementary; D005656:Fungal Proteins; D011506:Proteins