9 research outputs found
Codon Bias Patterns of 's Interacting Proteins
Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino
acid, are used differently across the variety of living organisms. The
biological meaning of this phenomenon, known as codon usage bias, is still
controversial. In order to shed light on this point, we propose a new codon
bias index, , that is based on the competition between cognate and
near-cognate tRNAs during translation, without being tuned to the usage bias of
highly expressed genes. We perform a genome-wide evaluation of codon bias for
, comparing with other widely used indices: , , and
. We show that and capture similar information by being
positively correlated with gene conservation, measured by ERI, and
essentiality, whereas, and appear to be less sensitive to
evolutionary-functional parameters. Notably, the rate of variation of and
with ERI allows to obtain sets of genes that consistently belong to
specific clusters of orthologous genes (COGs). We also investigate the
correlation of codon bias at the genomic level with the network features of
protein-protein interactions in . We find that the most densely
connected communities of the network share a similar level of codon bias (as
measured by and ). Conversely, a small difference in codon bias
between two genes is, statistically, a prerequisite for the corresponding
proteins to interact. Importantly, among all codon bias indices, turns
out to have the most coherent distribution over the communities of the
interactome, pointing to the significance of competition among cognate and
near-cognate tRNAs for explaining codon usage adaptation
Histogram of the <i>Z</i>-score for <i>Pr</i>(link|<i>d</i>) for each pair of genes and their respectively encoded proteins.
<p><i>d</i> is the Euclidean distance between pairs of genes in the space of the first two PCA components of codon bias, and <i>Pr</i>(link|<i>d</i>) is the conditional probability of having a link in the PIN between two proteins given that their encoding genes are localized within a distances <i>d</i> in the PC1-PC2 plane. The <i>Z</i>-score is obtained as <i>Z</i>[<i>Pr</i>(link|<i>d</i>)] = [<i>Pr</i>(link|<i>d</i>) − 〈<i>Pr</i>(link|<i>d</i>)〉<sub>Ω</sub>]/<i>σ</i><sub>Ω</sub>[<i>Pr</i>(link|<i>d</i>)]. The gray dashed lines mark the significance interval of ±3<i>σ</i>.</p
Features of top-scoring communities.
<p>Number of nodes (<i>n</i>), community score (<i>n</i> times the internal density), mean degree 〈<i>k</i>〉, predominant COG label and percentage; then, for ERI and the codon bias indices, mean values <math><msub><mi>x</mi><mo>¯</mo><mi>c</mi></msub></math> internal to the community and <i>Z</i> scores (between square brackets). Values <i>Z</i> > 1 are reported in bold.</p
Correlation between the various codon bias indices and ERI.
<p>Codon bias average values and standard deviation (error bars) are determined for each set of E.coli genes having the same ERI value. In each panel, the solid lines are linear regression fits, with <i>c</i> denoting the corresponding correlation coefficients. In the left panels, the fits are performed separately for the three groups of genes A (ERI < 0.2), B (0.2 < ERI < 0.9) and C (ERI > 0.9). Both <i>CompAI</i> and <i>tAI</i> monotonously increase with ERI, whereas <i>CAI</i> and <i>Nc</i> show a low correlation with ERI.</p
Codon bias indices for essential (E) and non-essential (NE) genes.
<p>Error bars are standard deviations within each group. Then mean value of codon bias is systematically higher for essential genes, however, only <i>CompAI</i> and <i>tAI</i> can effectively separate essential from non-essential genes. In fact, in the left panels the average codon bias values for essential and non-essential genes have a relative variation of about 5%, whereas, in the right panels such values are almost coincident and the errors overlap.</p
Relation between the various codon bias indices of genes and the degree <i>k</i> of the corresponding proteins in the PIN of E.coli.
<p>Solid lines are linear fits. <i>CompAI</i> and <i>tAI</i> of a gene definitely increase with the connectivity of the corresponding protein in the PIN, whereas the other two indices are less sensitive to this parameter.</p
Left plot: Eigenvalues of the correlation matrix between the codon bias indices on expressed sequences. Right plot: Projection of the first two PCA components on the individual codon bias indices.
<p>Recalling that <i>Nc</i> is anticorrelated with the other codon bias indices, PC1 results from a weighted and coherent contribution of all the indices, whereas, for PC2 the contribution of <i>CompAI</i> and <i>tAI</i> is opposite to that of <i>CAI</i> and <i>Nc</i>.</p
Histogram of <i>Pr</i>(COG|group) over the COGs for the three gene groups A, B, C.
<p>Each group is characterized by one or a few predominant COGs, indicated within parenthesis in the legend (assuming a threshold of 0.1 and excluding generic COGs R and S, for which function prediction is too general or missing).</p