Effect of the Transposable Element Environment of Human Genes on Gene Length and Expression

Abstract

Independent lines of investigation have documented effects of both transposable elements (TEs) and gene length (GL) on gene expression. However, TE gene fractions are highly correlated with GL, suggesting that they cannot be considered independently. We evaluated the TE environment of human genes and GL jointly in an attempt to tease apart their relative effects. TE gene fractions and GL were compared with the overall level of gene expression and the breadth of expression across tissues. GL is strongly correlated with overall expression level but weakly correlated with the breadth of expression, confirming the selection hypothesis that attributes the compactness of highly expressed genes to selection for economy of transcription. However, TE gene fractions overall, and for the L1 family in particular, show stronger anticorrelations with expression level than GL, indicating that GL may not be the most important target of selection for transcriptional economy. These results suggest a specific mechanism, removal of TEs, by which highly expressed genes are selectively tuned for efficiency. MIR elements are the only family of TEs with gene fractions that show a positive correlation with tissue-specific expression, suggesting that they may provide regulatory sequences that help to control human gene expression. Consistent with this notion, MIR fractions are relatively enriched close to transcription start sites and associated with coexpression in specific sets of related tissues. Our results confirm the overall relevance of the TE environment to gene expression and point to distinct mechanisms by which different TE families may contribute to gene regulation.

Widespread occurrence of power-law distributions in inter-repeat distances shaped by genome dynamics

“…Their lengths are found to follow power-laws (Cohen et al, 2005;Costantini et al, 2006). See also (Jjingo et al, 2011) for other forms of participation of the different TE classes to the overall genomic architecture. All the above mentioned forms of genomic complexity undoubtedly contribute to the observed differences in the power-law features among organisms or TE classes, which are only partially explained by the use of our simple insertionelimination model.…”

Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression

“…In one such study [8], our group identified MIRs to be the only TE-derived sequences whose presence shows a positive correlation to tissue-specific gene expression. Here, we provide evidence that this correlation is likely to be due to the propensity of MIRs to be exapted as enhancers that regulate cell-type and developmental-stage specific gene expression.…”

MIR retrotransposon sequences provide insulators to the human genome

“…First of all, a number of noncoding MIR sequences were found to be highly conserved, indicative of some functional, presumably regulatory, role (24). Later, it was shown that MIRs are enriched for open chromatin sites (25), encode regulatory RNAs (26), host gene promoters (27) and enhancers (28), and are also associated with tissue-specific expressed genes (29). Finally, and most importantly, MIRs are tRNA-derived SINEs (30) and their sequences include recognizable regulatory motifs, such as the promoter B-box element for Pol III binding, which are thought to be important for insulator activity.…”