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Rapid molecular evolution across amniotes of the IIS/TOR network.

ABSTRACT: The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid and extensive molecular evolution between reptiles (including birds) and mammals: (i) the IIS/TOR network, including the critical nodes insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates between reptiles and mammals; (ii) compared with a proxy for the rest of the genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast evolutionary rates; and (iii) signatures of positive selection and coevolution of the extracellular network suggest reptile- and mammal-specific interactions between members of the network. In reptiles, positively selected sites cluster on the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected sites clustered on the IGF2 binding surface, suggesting that these hormone-receptor binding affinities are targets of positive selection. Further, contrary to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we found positively selected sites clustered on the hormone binding surface of reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have sub- or neofunctionalized between mammals and reptiles and that this network may underlie fundamental life history and physiological differences between these amniote sister clades.

SUBMITTER: McGaugh SE

PROVIDER: S-EPMC4460498 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Rapid molecular evolution across amniotes of the IIS/TOR network.

McGaugh Suzanne E SE Bronikowski Anne M AM Kuo Chih-Horng CH Reding Dawn M DM Addis Elizabeth A EA Flagel Lex E LE Janzen Fredric J FJ Schwartz Tonia S TS Schwartz Tonia S TS

Proceedings of the National Academy of Sciences of the United States of America 20150519 22

The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid an ...[more]

PMID: 25991861

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Project description:BACKGROUND:The core functions of the insulin/insulin-like signaling and target of rapamycin (IIS/TOR) pathway are nutrient sensing, energy homeostasis, growth, and regulation of stress responses. This pathway is also known to interact directly and indirectly with the sex determination regulatory hierarchy. The IIS/TOR pathway plays a role in directing sexually dimorphic traits, including dimorphism of growth, metabolism, stress and behavior. Previous studies of sexually dimorphic gene expression in the adult head, which includes both nervous system and endocrine tissues, have revealed variation in sex-differential expression, depending in part on genotype and environment. To understand the degree to which the environmentally responsive insulin signaling pathway contributes to sexual dimorphism of gene expression, we examined the effect of perturbation of the pathway on gene expression in male and female Drosophila heads. RESULTS:Our data reveal a large effect of insulin signaling on gene expression, with greater than 50% of genes examined changing expression. Males and females have a shared gene expression response to knock-down of InR function, with significant enrichment for pathways involved in metabolism. Perturbation of insulin signaling has a greater impact on gene expression in males, with more genes changing expression and with gene expression differences of larger magnitude. Primarily as a consequence of the response in males, we find that reduced insulin signaling results in a striking increase in sex-differential expression. This includes sex-differences in expression of immune, defense and stress response genes, genes involved in modulating reproductive behavior, genes linking insulin signaling and ageing, and in the insulin signaling pathway itself. CONCLUSIONS:Our results demonstrate that perturbation of insulin signaling results in thousands of genes displaying sex differences in expression that are not differentially expressed in control conditions. Thus, insulin signaling may play a role in variability of somatic, sex-differential expression. The finding that perturbation of the IIS/TOR pathway results in an altered landscape of sex-differential expression suggests a role of insulin signaling in the physiological underpinnings of trade-offs, sexual conflict and sex differences in expression variability.

Project description:Background:Transposable elements (TEs) are primarily responsible for the DNA losses and gains in genome sequences that occur over time within and between species. TEs themselves evolve, with clade specific LTR/ERV, LINEs and SINEs responsible for the bulk of species-specific genomic features. Because TEs can contain regulatory motifs, they can be exapted as regulators of gene expression. While TE insertions can provide evolutionary novelty for the regulation of gene expression, their overall impact on the evolution of gene expression is unclear. Previous investigators have shown that tissue specific gene expression in amniotes is more similar across species than within species, supporting the existence of conserved developmental gene regulation. In order to understand how species-specific TE insertions might affect the evolution/conservation of gene expression, we have looked at the association of gene expression in six tissues with TE insertions in six representative amniote genomes. Results:A novel bootstrapping approach has been used to minimise the conflation of effects of repeat types on gene expression. We compared the expression of orthologs containing recent TE insertions to orthologs that contained older TE insertions, and the expression of non-orthologs containing recent TE insertions to non-orthologs with older TE insertions. Both orthologs and non-orthologs showed significant differences in gene expression associated with TE insertions. TEs were found associated with species-specific changes in gene expression, and the magnitude and direction of expression changes were noteworthy. Overall, orthologs containing species-specific TEs were associated with lower gene expression, while in non-orthologs, non-species specific TEs were associated with higher gene expression. Exceptions were SINE elements in human and chicken, which had an opposite association with gene expression compared to other species. Conclusions:Our observed species-specific associations of TEs with gene expression support a role for TEs in speciation/response to selection by species. TEs do not exhibit consistent associations with gene expression and observed associations can vary depending on the age of TE insertions. Based on these observations, it would be prudent to refrain from extrapolating these and previously reported associations to distantly related species.

Dataset Information

Rapid molecular evolution across amniotes of the IIS/TOR network.

Publications

Rapid molecular evolution across amniotes of the IIS/TOR network.

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