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Amino Acids as Placeholders

Base-Composition Pressures on Protein Length in Malaria Parasites and Prokaryotes

  • Original Research Article
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Applied Bioinformatics

Abstract

Background: The composition and sequence of amino acids in a protein may serve the underlying needs of the nucleic acids that encode the protein (the genome phenotype). In extreme form, amino acids become mere placeholders inserted between functional segments or domains, and — apart from increasing protein length — playing no role in the specific function or structure of a protein (the conventional phenotype).

Methods: We studied the genomes of two malarial parasites and 521 prokaryotes (144 complete) that differ widely in GC% and optimum growth temperature, comparing the base compositions of the protein coding regions and corresponding lengths (kilobases).

Results: Malarial parasites show distinctive responses to base-compositional pressures that increase as protein lengths increase. A low-GC% species (Plasmodium falciparum) is likely to have more placeholder amino acids than an intermediate-GC% species (P. vivax), so that homologous proteins are longer. In prokaryotes, GC% is generally greater and AG% is generally less in open reading frames (ORFs) encoding long proteins. The increased GC% in long ORFs increases as species’ GC% increases, and decreases as species’ AG% increases. In low- and intermediate-GC% prokaryotic species, increases in ORF GC% as encoded proteins increase in length are largely accounted for by the base compositions of first and second (amino acid-determining) codon positions. In high-GC% prokaryotic species, first and third (non-amino acid-determining) codon positions play this role.

Conclusion: In low- and intermediate-GC% prokaryotes, placeholder amino acids are likely to be well defined, corresponding to codons enriched in G and/or C at first and second positions. In high-GC% prokaryotes, placeholder amino acids are likely to be less well defined. Increases in ORF GC% as encoded proteins increase in length are greater in mesophiles than in thermophiles, which are constrained from increasing protein lengths in response to base-composition pressures.

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Acknowledgments

We thank J.R. Mortimer for programs that extract base compositions from codon usage tables. Queen’s University hosts the webpages of Dr Forsdyke where partial or full-text versions of some of the cited references may be found (http://post.queensu.ca/~forsdyke/homepage.htm).

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this article.

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Authors and Affiliations

  1. Department of Biochemistry, Queen’s University, Kingston, Ontario, Canada, K7L3N6

    Jonathan H. Rayment &  Donald R. Forsdyke

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  1. Jonathan H. Rayment
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  2. Donald R. Forsdyke
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Correspondence to Donald R. Forsdyke.

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Rayment, J.H., Forsdyke, D.R. Amino Acids as Placeholders. Appl-Bioinformatics 4, 117–130 (2005). https://doi.org/10.2165/00822942-200504020-00005

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