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A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns


Parallels between phylogeny and ontogeny have been discussed for almost two centuries, and a number of theories have been proposed to explain such patterns1. Especially elusive is the phylotypic stage, a phase during development where species within a phylum are particularly similar to each other2,3,4,5,6. Although this has formerly been interpreted as a recapitulation of phylogeny1, it is now thought to reflect an ontogenetic progression phase2, where strong constraints on developmental regulation and gene interactions exist2,3. Several studies have shown that genes expressed during this stage evolve at a slower rate, but it has so far not been possible to derive an unequivocal molecular signature associated with this stage7,8,9,10,11,12,13,14,15. Here we use a combination of phylostratigraphy16 and stage-specific gene expression data to generate a cumulative index that reflects the evolutionary age of the transcriptome at given ontogenetic stages. Using zebrafish ontogeny and adult development as a model, we find that the phylotypic stage does indeed express the oldest transcriptome set and that younger sets are expressed during early and late development, thus faithfully mirroring the hourglass model of morphological divergence2,3. Reproductively active animals show the youngest transcriptome, with major differences between males and females. Notably, ageing animals express increasingly older genes. Comparisons with similar data sets from flies and nematodes show that this pattern occurs across phyla. Our results indicate that an old transcriptome marks the phylotypic phase and that phylogenetic differences at other ontogenetic stages correlate with the expression of newly evolved genes.

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Figure 1: Transcriptome age profiles for the zebrafish ontogeny.
Figure 2: Relative expression of the genes from each phylostratum across the zebrafish ontogeny (same stages as in Fig. 1) for selected phylostrata with significant differences.
Figure 3: Transcriptome age profiles for the Drosophila ontogeny, based on the data in ref. 23.
Figure 4: Comparison of differences in TAI between females and males.

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

Themicroarray data for zebrafishwere depositedat theNCBIGene Expression Omnibus (GEO) repository under the accession number GSE24616.


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We thank B. Walderich for providing zebrafish, A. Nolte, E. Blohm-Sievers, B. Kleinhenz, L. Turner and J. Bryk for laboratory support, R. Bakarić has provided the phylostratigraphic map of C. elegans, and M. Domazet-Lošo and V. Dunjko have helped with statistics. L. Boell, F. Chang and A. Pozhitkov have made suggestions on the manuscript. This work was supported by Unity Through Knowledge Fund (grant No. 49), Adris Foundation and funds of the Max-Planck Society. Computational resources were provided by CSTMB and RBI (Phylostrat Cluster).

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T.D.-L. conceived the basic idea and conducted the experiments; D.T. contributed to the evaluation and interpretation of the results. Both authors wrote the manuscript.

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Correspondence to Tomislav Domazet-Lošo.

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The authors declare no competing financial interests.

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Domazet-Lošo, T., Tautz, D. A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468, 815–818 (2010).

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