Patterns and rates of intron divergence between humans and chimpanzees

Abstract

Background: Introns, which constitute the largest fraction of eukaryotic genes and which had been considered to be neutral sequences, are increasingly acknowledged as having important functions. Several studies have investigated levels of evolutionary constraint along introns and across classes of introns of different length and location within genes. However, thus far these studies have yielded contradictory results.

Results: We present the first analysis of human-chimpanzee intron divergence, in which differences in the number of substitutions per intronic site (Ki) can be interpreted as the footprint of different intensities and directions of the pressures of natural selection. Our main findings are as follows: there was a strong positive correlation between intron length and divergence; there was a strong negative correlation between intron length and GC content; and divergence rates vary along introns and depending on their ordinal position within genes (for instance, first introns are more GC rich, longer and more divergent, and divergence is lower at the 3' and 5' ends of all types of introns).

Conclusion: We show that the higher divergence of first introns is related to their larger size. Also, the lower divergence of short introns suggests that they may harbor a relatively greater proportion of regulatory elements than long introns. Moreover, our results are consistent with the presence of functionally relevant sequences near the 5' and 3' ends of introns. Finally, our findings suggest that other parts of introns may also be under selective constraints.

Figure 1

Mean K_i as a function of the ordinal position of introns (relative to other introns of the same gene). Single introns constitute a special category. All introns whose number within the gene was above 20 were pooled together, to avoid classes of sample size that was too different. The number above each bar represents the sample size of each category. First and single introns are the more divergent ones.

Figure 2

Average K_i for 20 classes of percentiles of length. Although there is a global increase in divergence with size, the shortest class of size presents an especially low divergence compared with all of the following classes of intron size.

Figure 3

Evolution of K_i within short introns (49 to 1029 nucleotides). The last bar of the histogram represents the cumulative data for all long introns. Data are presented for first and nonfirst introns separately, and are pooled in categories of increasing size class of 100 nucleotides for visual clarity. Nonfirst introns reach a plateau of mean K_i around 300 nucleotides, whereas this pattern is not as clearly discernable in first introns. nt, nucleotides.