(A) Schematic depicting transmission of three distinct transposon integrants occurring at various stages of tissue development (red, yellow and green circles), resulting in mitotically inherited insertions occurring at different allele frequencies in cell populations. This schematic was inspired by []. (B) During both normal development and in tumor formation, somatic transposition can result in TE mosaicism (illustrated by black circles in developing brain and hot pink circles in colon). The developmental time point and tissue specificity of mobilization help to define the variable allele frequencies in cells and tissues, and the diverse possible functional impacts of such somatic transposition.

Shown here are models of possible genomic and transcriptional variation due to mammalian transposon integrants. (A) Schematic of a gene without a TE insertion (top) and with a polymorphic TE insertion (bottom, indicated by blue rectangle). Black vertical rectangles, gene exons; horizontal black lines, genomic sequences including introns; red circles, target site duplications. (B – E) Effects of TE insertions on gene expression. (B) Typical gene expression with RNA splicing betwPeen exons, removing introns in the absence of a transposon insertion. (C) Premature transcriptional termination (Stop) triggered by an intronic TE acting at long genomic distances [,]. (D) TE-mediated transcriptional activation or upregulation (Go), due to internal promoter or enhancer activity. (E) Intergenic TEs may incorporate enhancer or silencer activities that variably affect gene expression upstream and/or downstream. These effects can help TEs influence transcriptional regulatory networks. (F) We hypothesize that many TE integrants may have no detectable effect on gene expression, depending on TE age and structure, tissue-specific differences and genomic context. See text for further details.

This schematic depicts hypothetical genomic counts (y-axis) and functional impacts (color scale) of TE insertions retained over evolutionary time, ranging from “old” (left) to “new” (right) integrants. The newest TE integrants are generated in somatic tissues (right). We hypothesize that their variable functional impacts (blue, neutral impact; red, high or deleterious impact) are influenced by the duration and strength of directional selection against deleterious insertions. In this way, surviving “older” insertions would be expected to have accumulated more mutations, to be fixed at a population level, and to exert minimal negative impacts on gene expression and function (green, blue, see ). By contrast, some young TE insertions, including somatic insertions, may disrupt gene expression more strongly (yellow, orange, red). Their allele frequencies would be significantly less than 100%. See text for further details.