Inter-species differences of co-expression of neighboring genes in eukaryotic genomes

Abstract

Background: There is increasing evidence that gene order within the eukaryotic genome is not random. In yeast and worm, adjacent or neighboring genes tend to be co-expressed. Clustering of co-expressed genes has been found in humans, worm and fruit flies. However, in mice and rats, an effect of chromosomal distance (CD) on co-expression has not been investigated yet. Also, no cross-species comparison has been made so far. We analyzed the effect of CD as well as normalized distance (ND) using expression data in six eukaryotic species: yeast, fruit fly, worm, rat, mouse and human.

Results: We analyzed 24 sets of expression data from the six species. Highly co-expressed pairs were sorted into bins of equal sized intervals of CD, and a co-expression rate (CoER) in each bin was calculated. In all datasets, a higher CoER was obtained in a short CD range than a long distance range. These results show that across all studied species, there was a consistent effect of CD on co-expression. However, the results using the ND show more diversity. Intra- and inter-species comparisons of CoER reveal that there are significant differences in the co-expression rates of neighboring genes among the species. A pair-wise BLAST analysis finds 8-30 % of the highly co-expressed pairs are duplicated genes.

Conclusion: We confirmed that in the six eukaryotic species, there was a consistent tendency that neighboring genes are likely to be co-expressed. Results of pair-wised BLAST indicate a significant effect of non-duplicated pairs on co-expression. A comparison of CD and ND suggests the dominant effect of CD.

Figure 1

The co-expression rates (CoERs) in the eleven human datasets are plotted as a function of chromosomal distance (CD): the results from the highly-correlated (HC) pairs (A), the zero-correlation (ZC) pairs (B) and the negatively-correlated (NC) pairs (C). The reference information is as follows: 1) Armstrong [21], 2) Ramasawamy [23], 3) Pomeroy [22], 4) Su (a) [17], 5) Yeoh [24], 6) Houmard [25], 7) Diette [26], 8) Dyrskjot [27], 9) Alizadeh (a) [28], 10) Alizadeh (b) [28], 11) Alizadeh (c) [28]. The weighted average and standard deviation of the CoER over the eleven datasets: the results from the HC pairs (D), the ZC pairs (E) and the NC pairs (F).

Figure 2

A comparison of the six species using the weighted average of each species. (A) the highly correlated pairs, (B) the zero correlation pairs and (C) the negatively correlated pairs. Note that worm2 represents the CoERs of the worm dataset without the pairs in operons and duplicates.

Figure 3

The co-expression rates shown in Figure 2(A) were re-plotted against the normalized distance. A value on the horizontal axis can be smaller than 1 because all possible pairs next to each other were involved in the calculation (i.e. we did not exclude a non-coding region, cetromere, etc from the calculation). Note that worm2 represents the CoERs of the worm dataset without the pairs in operons and duplicates.