No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals

Nested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and <i>Drosophila</i> microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of...

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Main Author: Raquel Assis
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/12/9/1381
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author Raquel Assis
author_facet Raquel Assis
author_sort Raquel Assis
collection DOAJ
description Nested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and <i>Drosophila</i> microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of transcriptional interference driving rapid expression divergence between <i>Drosophila</i> nested genes, illustrating that accurate expression estimation of overlapping genes can enhance detection of their relationships. Hence, here I apply an analogous approach to strand-specific RNA-seq data from human and mouse to revisit the role of transcriptional interference in the evolution of mammalian nested genes. A genomic survey reveals that whereas mammalian nested genes indeed accrued over evolutionary time, they are retained at lower frequencies than in <i>Drosophila</i>. Though several properties of mammalian nested genes align with observations in <i>Drosophila</i> and with expectations under transcriptional interference, contrary to both, their expression divergence is not statistically different from that between unnested genes, and also does not increase after nesting. Together, these results support the hypothesis that lower selection efficiencies limit rates of gene expression evolution in mammals, leading to their reliance on immediate eradication of deleterious nested genes to avoid transcriptional interference.
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spelling doaj.art-15fb457018ed4747ae2afa9d5ae289572023-11-22T13:14:12ZengMDPI AGGenes2073-44252021-09-01129138110.3390/genes12091381No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in MammalsRaquel Assis0Department of Electrical Engineering and Computer Science, Institute for Human Health and Disease Intervention, Florida Atlantic University, Boca Raton, FL 33431, USANested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and <i>Drosophila</i> microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of transcriptional interference driving rapid expression divergence between <i>Drosophila</i> nested genes, illustrating that accurate expression estimation of overlapping genes can enhance detection of their relationships. Hence, here I apply an analogous approach to strand-specific RNA-seq data from human and mouse to revisit the role of transcriptional interference in the evolution of mammalian nested genes. A genomic survey reveals that whereas mammalian nested genes indeed accrued over evolutionary time, they are retained at lower frequencies than in <i>Drosophila</i>. Though several properties of mammalian nested genes align with observations in <i>Drosophila</i> and with expectations under transcriptional interference, contrary to both, their expression divergence is not statistically different from that between unnested genes, and also does not increase after nesting. Together, these results support the hypothesis that lower selection efficiencies limit rates of gene expression evolution in mammals, leading to their reliance on immediate eradication of deleterious nested genes to avoid transcriptional interference.https://www.mdpi.com/2073-4425/12/9/1381nested genesoverlapping genestranscriptional interferencegene expression
spellingShingle Raquel Assis
No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
Genes
nested genes
overlapping genes
transcriptional interference
gene expression
title No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
title_full No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
title_fullStr No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
title_full_unstemmed No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
title_short No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
title_sort no expression divergence despite transcriptional interference between nested protein coding genes in mammals
topic nested genes
overlapping genes
transcriptional interference
gene expression
url https://www.mdpi.com/2073-4425/12/9/1381
work_keys_str_mv AT raquelassis noexpressiondivergencedespitetranscriptionalinterferencebetweennestedproteincodinggenesinmammals