The Transposable Element Environment of Human Genes Differs According to Their Duplication Status and Essentiality

Abstract

Transposable elements (TEs) are major components of eukaryotic genomes and represent approximately 45% of the human genome. TEs can be important sources of novelty in genomes and there is increasing evidence that TEs contribute to the evolution of gene regulation in mammals. Gene duplication is an evolutionary mechanism that also provides new genetic material and opportunities to acquire new functions. To investigate how duplicated genes are maintained in genomes, here, we explored the TE environment of duplicated and singleton genes. We found that singleton genes have more short-interspersed nuclear elements and DNA transposons in their vicinity than duplicated genes, whereas long-interspersed nuclear elements and long-terminal repeat retrotransposons have accumulated more near duplicated genes. We also discovered that this result is highly associated with the degree of essentiality of the genes with an unexpected accumulation of short-interspersed nuclear elements and DNA transposons around the more-essential genes. Our results underline the importance of taking into account the TE environment of genes to better understand how duplicated genes are maintained in genomes.

Keywords: LINE; SINE; essential genes; gene duplication; gene evolution; transposable elements.

Fig. 1.

Distribution of the TE density in gene environments of duplicated and singleton genes including their 2- or 10-kb flanking regions. Dupl, duplicated genes; singl, singleton genes. Asterisks indicate a significant difference between the TE density distributions.

Fig. 2.

Gene Ontology (GO) term enrichment analysis according to the duplicate status for the Biological Process ontology and 2-kb flanking region size (dataset 1). Comparison of function for duplicated genes (light gray bars) and singleton genes (black bars) for TE-rich, TE-medium, and TE-poor densities. Height of bars corresponds for each function to the percentage of involved genes. Asterisks indicate statistically significant differences (Fisher’s exact tests, FDR <0.01) and black triangles indicate statistically significant differences (Fisher’s exact tests, FDR <0.01) for comparison where one gene per each gene family is randomly chosen. Multicell. org. process, multicellular organismal process; reg. cellular process, regulation of cellular process; reg. biological process, regulation of biological process; CSR signaling pathway, cell surface receptor signaling pathway; reg. biological quality, regulation of biological quality; cell. comp. organization, cellular component organization; cell. protein localization, cellular protein localization; cell. macro. localization, cellular macromolecule localization; cell. macro. meta. process, cellular macromolecule metabolic process; intracell. signal transduction, intracellular signal transduction; macro. metabolic process, macromolecule metabolic process.

Fig. 3.

Gene Ontology (GO) term enrichment analysis according to the TE context for the Biological Process ontology and 2-kb flanking region size. Comparison of function between genes according to TE density; top, TE-rich genes versus TE-medium genes; middle, TE-rich genes versus TE-poor genes; bottom, TE-medium genes versus TE-poor genes. Black bars, TE-rich genes; Light gray bars, TE-medium genes; White bars, TE-poor genes. Asterisks indicate statistically significant differences (Fisher’s exact tests, FDR <0.01). Reg. cell. biosynthetic process, regulation of cellular biosynthetic process; reg. biosynthetic process, regulation of biosynthetic process; reg. metabolic process, regulation of metabolic process; reg. cell. process, regulation of cellular process; reg. biological process, regulation of biological process; cell. response to stimulus, cellular response to stimulus; CSR signaling pathway, cell surface receptor signaling pathway; multicell. org. dev., multicellular organism development; multicell. org. process, multicellular organismal process; transcr. RNA pol. II, transcription by RNA polymerase II; transcr. DNA-templated, transcription, DNA-templated; macro. metabolic process, macromolecule metabolic process; OS metabolic process, organic substance metabolic process.

Fig. 4.

Boxplots of TE densities according to essentiality categories for 2-kb flanking region gene environment. Outlier points are not shown. NoE, Non-Essential genes; CRE, Conditional Restricted-Essential genes; CME, Conditional Medium-Essential genes; CLE, Conditional Largely Essential genes; E, Essential genes.

Fig. 5.

Divergence of TE copies according to superfamilies in the entire genome (--strict option of the tool One Code To Find Them All).