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Evolutionary dynamics of coding and non-coding transcriptomes

Key Points

  • The recent advent of high-throughput sequencing-based approaches enables detailed qualitative and quantitative comparisons of transcriptomes and gene regulatory mechanisms between distant species.

  • Initial transcriptome comparisons based on RNA sequencing have revealed different rates of expression evolution for different types of transcripts, mammalian lineages and organs due to global differences in selective pressures.

  • The differentiation of mammalian sex chromosomes from ordinary ancestral autosomes entailed substantial and chromosome-wide remodelling of gene contents and expression patterns owing to the emerging sex-related selective forces.

  • The search for adaptive expression changes is challenging because of various confounding factors. Nevertheless, various phenotypically relevant expression changes have been identified, which warrant further experimental validation and characterization.

  • Although regulatory mechanisms underlying gene expression are now fairly well understood overall, only a few studies have attempted to jointly analyse transcriptome evolution and the underlying regulatory changes. These initial studies suggest that adaptive gene expression evolution may be driven by both cis- and trans-regulatory changes.

  • One of the most challenging but also most important future research directions is the detailed experimental characterization of detected transcriptome changes, which will ultimately reveal their actual biological and evolutionary relevance.

Abstract

Gene expression changes may underlie much of phenotypic evolution. The development of high-throughput RNA sequencing protocols has opened the door to unprecedented large-scale and cross-species transcriptome comparisons by allowing accurate and sensitive assessments of transcript sequences and expression levels. Here, we review the initial wave of the new generation of comparative transcriptomic studies in mammals and vertebrate outgroup species in the context of earlier work. Together with various large-scale genomic and epigenomic data, these studies have unveiled commonalities and differences in the dynamics of gene expression evolution for various types of coding and non-coding genes across mammalian lineages, organs, developmental stages, chromosomes and sexes. They have also provided intriguing new clues to the regulatory basis and phenotypic implications of evolutionary gene expression changes.

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Figure 1: Global patterns of evolution for different aspects of the transcriptome.
Figure 2: Rates of genome and transcriptome evolution in different mammalian lineages.
Figure 3: Different rates of evolution in major mammalian organs and 'promiscuous' transcription in the testis.
Figure 4: Origins and functional evolution of mammalian sex chromosomes.
Figure 5: Expression modules and co-expression networks.
Figure 6: Example of a gene expression change associated with a change in histone methylation.

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Acknowledgements

The authors apologize to colleagues whose work could not be discussed or cited owing to space constraints and/or the focus of this Review. This work was supported by grants from the European Research Council (Starting Grant: 242597, SexGenTransEvolution) and the Swiss National Science Foundation (Grant: 130287) to H.K. A.N. was supported by the Swiss National Science Foundation (Ambizione grant: 142636).

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Correspondence to Anamaria Necsulea or Henrik Kaessmann.

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Glossary

Cis- and trans-acting regulatory mechanisms

Mechanisms that regulate gene expression. Cis-acting regulatory elements (such as promoters or enhancers) are DNA sequences located on the same chromosome and generally in the vicinity of the target gene, and they recruit molecules that can modulate the expression of the target gene. Trans-acting factors (such as transcription factors or microRNAs) control gene expression by binding to cis-acting elements; their genomic localization is independent of that of the regulated genes.

Negative selection

A type of natural selection that eliminates deleterious mutations.

Amniote

A subclass of vertebrate species characterized by the presence of an amnion, which is a protective envelope that encloses the embryo. They include reptiles, birds and mammals but not amphibians.

Spearman's rank correlation coefficients

In transcriptome analyses, non-parametric statistics (in which the data are not required to follow specific statistical distributions) are often preferred. For example, expression levels may be compared across samples using Spearman's rank correlation coefficient, a statistical measure that estimates the similarity between the ranks of the genes, rather than between their absolute expression values.

Exon skipping

A form of alternative splicing in which internal exons are alternatively included or excluded (skipped) in the mature mRNA.

Effective population size

(Ne). A measure of the genetic diversity of a population. It is typically defined as the number of individuals in an idealized population (that is, one with random mating, equal sex distribution, etc.) that would show the same amount of genetic diversity as the population under consideration.

Therians

A subclass of mammals that comprises placental mammals (eutherians) and marsupials (metatherians); that is, mammals that give birth to live young without using a shelled egg. The remaining major mammalian lineage is that of the egg-laying monotremes (prototherians).

Dosage sensitive

Pertaining to genes for which the associated phenotypes are directly affected by modifications of their transcriptional output (such as changes in the number of active copies in the genome). For example, genes that encode subunits of a protein complex are dosage sensitive, as individual gene duplication leads to an imbalance among the parts of the complex.

X chromosome dosage compensation

A process that compensates for the loss of most Y-chromosome genes after sex chromosome differentiation from ancestral autosomes (that is, the reduction from two copies on sex chromosome precursors to one gene copy on the X chromosome in males).

Positive selection

A type of natural selection that favours the spread to fixation of an allele that increases the fitness of individuals.

Hemizygous

A condition in which there is only one copy of a gene in an otherwise diploid cell or organism (for example, all genes on the X chromosomes of male mammals).

Meiotic sex chromosome inactivation

(MSCI). A process leading to the transcriptional silencing of the X and Y chromosomes during the meiotic phase of spermatogenesis.

Genetic drift

An evolutionary process through which the frequency of an allele in a population changes through time simply by a random sampling effect; that is, some alleles can increase or decrease in frequency by chance over time, even in the absence of an effect on the fitness of the individuals. The magnitude of this phenomenon is stronger for lower effective population sizes.

Ornstein–Uhlenbeck processes

Mathematical models that describe random variations of a quantitative variable towards an optimum value. This model is widely used to describe evolutionary processes, as it can incorporate both genetic drift and natural selection.

GC-biased gene conversion

(gBGC). A non-adaptive evolutionary process that favours the fixation of GC alleles over AT alleles in highly recombining regions; it is likely to result from biased mismatch repair in heterozygous individuals during meiotic recombination.

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Necsulea, A., Kaessmann, H. Evolutionary dynamics of coding and non-coding transcriptomes. Nat Rev Genet 15, 734–748 (2014). https://doi.org/10.1038/nrg3802

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