Evolutionarily conserved genes preferentially accumulate introns

Abstract

Introns that interrupt eukaryotic protein-coding sequences are generally thought to be nonfunctional. However, for reasons still poorly understood, positions of many introns are highly conserved in evolution. Previous reconstructions of intron gain and loss events during eukaryotic evolution used a variety of simplified evolutionary models that yielded contradicting conclusions and are not suited to reveal some of the key underlying processes. We combine a comprehensive probabilistic model and an extended data set, including 391 conserved genes from 19 eukaryotes, to uncover previously unnoticed aspects of intron evolution--in particular, to assign intron gain and loss rates to individual genes. The rates of intron gain and loss in a gene show moderate positive correlation. A gene's intron gain rate shows a highly significant negative correlation with the coding-sequence evolution rate; intron loss rate also significantly, but positively, correlates with the sequence evolution rate. Correlations of the opposite signs, albeit less significant ones, are observed between intron gain and loss rates and gene expression level. It is proposed that intron evolution includes a neutral component, which is manifest in the positive correlation between the gain and loss rates and a selection-driven component as reflected in the links between intron gain and loss and sequence evolution. The increased intron gain and decreased intron loss in evolutionarily conserved genes indicate that intron insertion often might be adaptive, whereas some of the intron losses might be deleterious. This apparent functional importance of introns is likely to be due, at least in part, to their multiple effects on gene expression.

Figure 1.

Scatter plots of the gene-specific intron gain and loss rates versus other genomic variables. (A) Intron gain rate vs. intron loss rate; (B) intron gain rate vs. gene evolution rate (ER); (C) intron gain rate vs. gene expression level (EL); (D) intron gain rate vs. number of paralogs (NP); (E) intron loss rate vs. gene evolution rate; (F) intron loss rate vs. gene expression level. Units of the variables: gain rate (arbitrary units); loss rate (arbitrary units); ER (average over a KOG of median normalized JTT distances); EL (maximum among paralogs of standardize log-values of expression readings); NP (average number of paralogs across seven eukaryotic species) (for details, see Wolf et al. 2006).

Figure 2.

Coefficients of the multiple linear regression of gene-specific intron gain rate (light gray), and of gene-specific intron loss rate (dark gray). The bars show the 95% confidence interval, and the line within each bar shows the optimal value.