2020, Henrik·Kaessmann, Nature

Transcriptome and translatome co-evolution in mammals

10.1038/s41586-020-2899-z

https://www.nature.com/articles/s41586-020-2899-z

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GitHub

https://github.com/evgenyleushkin/translatome

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Database

https://ex2plorer.kaessmannlab.org/

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1. The "however"

Gene-expression programs define shared and species-specific phenotypes, but their evolution remains largely uncharacterized beyond the transcriptome layer.

Expression studies have so far focused primarily on analyses of transcriptomes and their regulation, and these studies have provided many insights into the dynamics of evolutionary changes in gene expression and the associated phenotypic implications in mammals. However, given that the expression of protein-coding genes may frequently be regulated at layers that succeed transcription, and that it is ultimately protein abundance that is phenotypically relevant, transcriptome studies provide an incomplete picture of expression evolution. Evolutionary shifts in mRNA expression that are due to transcriptional regulatory mutations may be, for example, offset by post-transcriptional regulatory mutations that reconstitute (optimal) protein levels.

2. Findings

• 1. Our within-species analyses reveal that translational regulation is widespread in the different organs, in particular across the spermatogenic cell types of the testis.
• 2. The between-species divergence in gene expression is around 20% lower at the translatome layer than at the transcriptome layer owing to extensive buffering between the expression layers, which especially preserved old, essential and housekeeping genes.
• 3. Translational upregulation specifically counterbalanced global dosage reductions during the evolution of sex chromosomes and the effects of meiotic sex-chromosome inactivation during spermatogenesis.
• 4. Despite the overall prevalence of buffering, some genes evolved faster at the translatome layer— potentially indicating adaptive changes in expression; testis tissue shows the highest fraction of such genes.
• 5. Further analyses incorporating mass spectrometry proteomics data establish that the co-evolution of transcriptomes and translatomes is reflected at the proteome layer.

3. Experiments and datasets

Figure. 1 abc

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4.1 In somatic tissues: Translational regulation increases the variation from transcriptome layer levels to translatome layer

Figure. 1 cd

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4.2 In testis: Translational regulation decreases the variation from transcriptome layer levels to translatome layer

Figure. 1d

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解释：An anticorrelation between transcript abundances and their translational efficiencies

Extended Data Fig. 3e

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The four species with reduced expression variation at the translatome relative to the transcriptome layer show the strongest anticorrelations

Extended Data Fig. 3f

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4.3 In spermatocyte and spermatid: Translational regulation decreases the variation from transcriptome layer levels to translatome layer

Extended Data Fig. 3g

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5.1 For all tissues, the translational evolution is slower than transcriptional evolution

Figure. 2a

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5.2 Testes show the most rapid expression evolution across all tissues across species

Figure. 2a

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5.3 Translatome significantly regulate proteome than transcriptome

Figure. 2g

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Extended Data Fig. 9

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6.1 Housekeeping genes evolve slow

Figure. 3a

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6.2 Tissue-specific genes evolve faster than housekeeping genes

Figure. 3a
brain-specific genes evolve considerably more slowly than genes that are specific to liver or testis

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6.3 In testis, celltype-specific genes evolve faster than testis general genes

Extended Data Fig. 3l

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6.4 Brain evolve every slow

Notably, all of the aforementioned contrasts between categories at the transcriptome and translatome layers are also reflected at the pro- teome layer. That is, comparisons of human and mouse proteome data for the brain reveal higher rank preservation for broadly expressed, essential, haploinsufficient and old genes than for tissue-specific, mutationally tolerant, haplosufficient and young genes, respectively.

Figure. 3b

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6.5 Spatial expression has the highest effect on evolutionary rates

Figure. 3c

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7.1 Present-day levels of X-chromosome expression are significantly more similar to ancestral levels at the translatome layer than at the transcriptome layer in eutherian organs

Figure. 4a

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7.2 Testes show the highest translational upregulation for genes in X-chromosome

Figure. 4a

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Deduced reasons: Testis is dominated by spermatocytes and spermatid in which X-chromosome is inactivated.

8. Data availability

https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-7247
https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-7247/sdrf?full=true