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, 99 (9), 6118-23

Intron Evolution as a Population-Genetic Process

Affiliations

Intron Evolution as a Population-Genetic Process

Michael Lynch. Proc Natl Acad Sci U S A.

Abstract

Debate over the mechanisms responsible for the phylogenetic and genomic distribution of introns has proceeded largely without consideration of the population-genetic forces influencing the establishment and retention of novel genetic elements. However, a simple model incorporating random genetic drift and weak mutation pressure against intron-containing alleles yields predictions consistent with a diversity of observations: (i) the rarity of introns in unicellular organisms with large population sizes, and their expansion after the origin of multicellular organisms with reduced population sizes; (ii) the relationship between intron abundance and the stringency of splice-site requirements; (iii) the tendency for introns to be more numerous and longer in regions of low recombination; and (iv) the bias toward phase-0 introns. This study provides a second example of a mechanism whereby genomic complexity originates passively as a "pathological" response to small population size, and raises difficulties for the idea that ancient introns played a major role in the origin of genes by exon shuffling.

Figures

Figure 1
Figure 1
Scaled probabilities of establishment (left axis, and lower curves) and loss (right axis, and upper curves) of introns in diploid (filled points and solid lines) and haploid populations (open points and dashed lines). The curved lines are the theoretical results outlined in the text, whereas the plotted values are results from computer simulations. For this particular set of simulations, n = 10−5 and s = 10−6.
Figure 2
Figure 2
Steady-state distributions for the frequency of the intron-free state obtained by use of Eq. 3. Results are given for two population sizes, with b = d = 10−10 and s = 10−7. The distribution can be viewed as the probability that the population has a particular gene frequency at a particular time or as the fraction of time that the population spends in a particular state.
Figure 3
Figure 3
The equilibrium rate of turnover for introns at a specific site, with b and d representing the per generation rates of origin (by insertion) and elimination (by deletion) of introns.
Figure 4
Figure 4
The consequences of an intron-expansion event for the coding sequence of two flanking exons. (Upper) Regardless of the intron phase, a 2-nucleotide (or 1-nucleotide) expansion will result in a frameshift in all downstream codons. (Lower) A 3-nucleotide expansion results in the loss of a codon if the intron is in phase 0, but a loss of a codon plus one altered codon sequence if the intron is in phase 1 or 2.
Figure 5
Figure 5
The scaled probability of intron-sliding for a two-step process, as described in the text. The mutation rate to null alleles is u (in all plotted cases equal to 10−5), whereas the rate of compensatory mutation is r. The filled points are the results from computer simulations, whereas the dashed lines are the analytical approximations, and the arrows denote the uncorrected large-population size result, r/√u.

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