The relationship between third-codon position nucleotide content, codon bias, mRNA secondary structure and gene expression in the drosophilid alcoholdehydrogenase genes Adh and Adhr
Db. Carlini et al., The relationship between third-codon position nucleotide content, codon bias, mRNA secondary structure and gene expression in the drosophilid alcoholdehydrogenase genes Adh and Adhr, GENETICS, 159(2), 2001, pp. 623-633
To gain insights into the relationship between codon bias, mRNA secondary s
tructure, third-codon position nucleotide distribution, and gene expression
, we predicted secondary structures in two related drosophilid genes, Adh a
nd Adhr, which differ in degree of codon bias and level of gene expression.
Individual structural elements (helices) were inferred using the comparati
ve method. For each gene, four types of randomization simulations were perf
ormed to maintain/remove codon bias and/or to maintain or alter third-codon
position nucleotide composition (M). In the weakly expressed, weakly biase
d gene Adhr; the potential for secondary structure formation was found to b
e much stronger than in the highly expressed, highly biased gene Adh. This
is consistent with the observation of approximately equal G and C percentag
es in Adhr (similar to 31% across species), whereas in Adh the N3 distribut
ion is shifted toward C (42% across species). Perturbing the N3 distributio
n to approximately equal amounts of A, G, C, and T increases the potential
for secondary structure formation in Adh, but decreases it in Adhr. On the
other hand, simulations that reduce codon bias without changing N3 content
indicate that codon bias per se has only a weak effect on the formation of
secondary structures. These results suggest that, for these two drosophilid
genes, secondary Structure is a relatively independent, negative regulator
of gene expression. Whereas the degree of codon bias is positively correla
ted with level of gene expression, strong individual secondary Structural e
lements may be selected for to retard mRNA translation and to decrease gene
expression.