Amino acids as placeholders: base-composition pressures on protein length in malaria parasites and prokaryotes.
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.


CONCLUSIONS
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.
Rayment
Jonathan H
JH
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Forsdyke
Donald R
DR
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001419:Bacteria / Q000235:genetics*; D001482:Base Composition / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012641:Selection, Genetic; D020539:Sequence Analysis, Protein / Q000379:methods; D013045:Species Specificity
D000596:Amino Acids; D011506:Proteins