The Role of Gene Conversion between Transposable Elements in Rewiring Regulatory Networks

Abstract

Nature has found many ways to utilize transposable elements (TEs) throughout evolution. Many molecular and cellular processes depend on DNA-binding proteins recognizing hundreds or thousands of similar DNA motifs dispersed throughout the genome that are often provided by TEs. It has been suggested that TEs play an important role in the evolution of such systems, in particular, the rewiring of gene regulatory networks. One mechanism that can further enhance the rewiring of regulatory networks is nonallelic gene conversion between copies of TEs. Here, we will first review evidence for nonallelic gene conversion in TEs. Then, we will illustrate the benefits nonallelic gene conversion provides in rewiring regulatory networks. For instance, nonallelic gene conversion between TE copies offers an alternative mechanism to spread beneficial mutations that improve the network, it allows multiple mutations to be combined and transferred together, and it allows natural selection to work efficiently in spreading beneficial mutations and removing disadvantageous mutations. Future studies examining the role of nonallelic gene conversion in the evolution of TEs should help us to better understand how TEs have contributed to evolution.

Keywords: gene conversion; rewiring regulatory network; transposable elements.

Fig. 1.

—An example of the rewiring of a gene regulatory network where a DNA-binding protein (black circles) regulates a number of genes (blue rectangles) by binding to DNA motifs (black stripes). Some of the motifs and binding events may be lost (represented by gray stripes and circles), whereas new motifs and binding events may appear, which can sometimes wire new genes into the network. TEs (gray rectangles) may play an important role in providing and dispersing these new motifs.

Fig. 2.

—Pattern of polymorphism observed with nonallelic gene conversion. Nucleotide polymorphism of four individual genomes for three TE copies is shown. Nucleotides in red, purple, blue are polymorphisms due to point mutations in Copies A, B, and C, respectively. The mutations in Copy A in Genome 2 are transferred to Copy B, whereas the mutations in Copy C in Genome 3 are transferred to copy B by nonallelic gene conversions.

Fig. 3.

—Rewiring of a regulatory network mediated by TEs without nonalleic gene conversion (a) and with nonallelic gene conversion (b). Initially, a DNA-binding protein (black circle) binds to a particular motif (yellow stripes) contained within a given TE family (gray rectangles). A new motif (red stripe) that confers an advantage to the system (e.g., improves the binding efficiency) arises by mutation to the initial motif. This new motif can be preferentially utilized by being dispersed to several new genomic locations by transposition of the TE copy (gray arrows) containing the motif (a), or by being dispersed by transposition and also by replacing the old motif with the new motif via nonallelic gene conversion (blue arrows) (b).

Fig. 4.

—The substitution rate (F(s)) as a function of s, the selection coefficient that a single mutation confers. N = 1,000 was assumed for computing F(s). F(s) is standardized such that $F(0)=1$.