Trends in Genetics
Volume 30, Issue 10, October 2014, Pages 439-452
Journal home page for Trends in Genetics

Feature Review
Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications

https://doi.org/10.1016/j.tig.2014.08.004Get rights and content

Highlights

  • lncRNAs show weak selective constraint, even when clearly functional.

  • Gain and loss of lncRNA genes occurs at very high pace during evolution.

  • lncRNAs mostly evolve de novo.

  • Bidirectional promoters and transposable elements (TEs) promote the birth of lncRNAs.

  • Genomes rich in TEs may have more complex and malleable transcriptomes.

Thousands of genes encoding long noncoding RNAs (lncRNAs) have been identified in all vertebrate genomes thus far examined. The list of lncRNAs partaking in arguably important biochemical, cellular, and developmental activities is steadily growing. However, it is increasingly clear that lncRNA repertoires are subject to weak functional constraint and rapid turnover during vertebrate evolution. We discuss here some of the factors that may explain this apparent paradox, including relaxed constraint on sequence to maintain lncRNA structure/function, extensive redundancy in the regulatory circuits in which lncRNAs act, as well as adaptive and non-adaptive forces such as genetic drift. We explore the molecular mechanisms promoting the birth and rapid evolution of lncRNA genes, with an emphasis on the influence of bidirectional transcription and transposable elements, two pervasive features of vertebrate genomes. Together these properties reveal a remarkably dynamic and malleable noncoding transcriptome which may represent an important source of robustness and evolvability.

Section snippets

How large is the lncRNA iceberg?

The past decade has witnessed remarkable progress in genomics, providing geneticists with the opportunity to probe genome function with unprecedented depth and detail. One of the most striking observations gleaned from transcriptome studies is that a much larger fraction of the genome is represented as exons in mature RNAs than what would be predicted from the amount of DNA covered by the exons of protein-coding genes (both translated and untranslated). A major component emerging from such

Evolutionary conservation of lncRNAs

Comparative evolutionary sequence analysis has proven useful for predicting or evaluating functionality of both coding and noncoding sequences 44, 45. Many studies have sought to measure functional constraint on lncRNA exon sequences within and across species. Faint but significant signals of purifying selection acting on lncRNAs have been detected in global interspecific sequence comparisons 5, 11, 27, 46, 47. Evolutionary constraint on lncRNA sequence, when detectable, is markedly stronger

Mechanisms of lncRNA origination

The rapid evolutionary turnover of lncRNA genes raises the question of the molecular mechanisms driving their birth and death. The processes underlying lncRNA extinction have not yet been explored in a systematic way, but one can envisage a combination of sequence erosion by point mutations, TE disruption, and genomic deletions as the most obvious mechanisms (e.g., [60] for TEs). Epigenetic modification of chromatin structure at local or distal cis-regulatory elements may also lead to

Bidirectional transcription as a profuse source of lncRNAs

Bidirectional gene organization is a common feature of mammalian genomes [85]. Approximately 10% of protein-coding genes in the human genome are arranged in a ‘head-to-head’ orientation and are apparently controlled by a bidirectional promoter [86]. This is far more than predicted under random expectation, and many bidirectional gene pairs have been stably associated over long periods of evolution 86, 87, 88, 89. The key feature underlying this organization is the inherent property of many

TEs as important drivers of lncRNA evolution

Between one and two thirds of mammalian genomes are made up of TEs or their remnants 117, 118. TEs are divided into several classes (retroelements, endogenous retroviruses, DNA transposons, etc.) and hundreds of different families that have propagated at different time-points throughout vertebrate evolution. Through their capacity to move and amplify, as well as their ability to introduce regulatory sequences upon insertion, TEs represent a considerable force shaping genome architecture and

Volatile evolution of lncRNAs: implications and speculations

The data summarized above and elsewhere 79, 104, 134 paint a provocative picture of genome evolution whereby novel transcription units (i.e., genes, in the loosest definition) emerge and disappear at a much faster pace than was previously appreciated. Estimating how many of these recently evolved genes are truly important for organismal fitness now or at any time-point along a particular species lineage is one of the greatest challenges of 21st century biology. It will necessitate the

Acknowledgments

We apologize to colleagues who have produced primary research on the topic but could not be cited or discussed owing to space limitations. We thank Adam M. Jenkins and Marc A.T. Muskavitch for communication of the amount of lncRNAs in Anopheles gambiae before publication. We thank Edward B. Chuong for critical comments on the manuscript. This work was supported by the National Institutes of Health (R01 GM077582).

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