Transposable elements donate lineage-specific regulatory sequences to host genomes

Abstract

The evolutionary implications of transposable element (TE) influences on gene regulation are explored here. An historical perspective is presented to underscore the importance of TE influences on gene regulation with respect to both the discovery of TEs and the early conceptualization of their potential impact on host genome evolution. Evidence that points to a role for TEs in host gene regulation is reviewed, and comparisons between genome sequences are used to demonstrate the fact that TEs are particularly lineage-specific components of their host genomes. Consistent with these two properties of TEs, regulatory effects and evolutionary specificity, human-mouse genome wide sequence comparisons reveal that the regulatory sequences that are contributed by TEs are exceptionally lineage specific. This suggests a particular mechanism by which TEs may drive the diversification of gene regulation between evolutionary lineages.

Fig. 1

Historically relevant implications of TEs for gene regulation. (A) Variegated pigmentation of maize kernels resulting from TE activity. (B) COT curve showing the dynamics of DNA reassociation used to infer the presence of repetitive DNA in eukaryotic genomes. Repetitive DNA reassociates more rapidly than single copy DNA.

Fig. 2

Density of repetitive DNA in human genome promoter regions. 4,737 human promoter sequences, beginning at position −2,000 bp and ending at position +1,000 bp with respect to the transcriptional start sites, were scanned for the presence of TE derived sequences (A) and low complexity repetitive sequences (B). In each promoter sequence, residues that overlap with TE (A) and low complexity sequences are colored black (B).

Fig. 3

Sequence alignments that show the relationship of TE-derived sequences, host promoter sequences and experimentally characterized cis-binding sites. TE family consensus sequences are aligned with host genome sequences. Cis-binding sites are characterized for human sequences and their locations in the alignments are boxed. (A) An Alu element that inserted after the diversification of the human and mouse lineages donated three cis-binding sites to human (Hs) CD8α gene regulatory sequences. (B) A L2 element that inserted prior to the diversification of the human (Hs) and mouse (Mm) lineages, and was then conserved, donated three cis-binding sites to the GPIIb gene regulatory region. (C) A MaLR element that inserted prior to the diversification of the human and mouse lineages but was only conserved in the human (Hs) lineage donated four cis-binding sites to the γ^A-globin enhancer region.