Thread by @mirimiam

🚨Exciting pre-print from the lab!👉"Pervasive evolution of tissue-specificity of ancestral genes differentially shaped vertebrates and insects". Deep comparative #transcriptomics across #bilateria by @FedeMantica et al @CRGenomica. 👀biorxiv.org/content/10.110…. Summary👇

How has tissue-specific gene expression evolved since the origin of bilaterian animals all the way to extant vertebrates and insects? To address this, we assembled a vast RNA-seq dataset covering 8 tissues and 20 species, generating 95 new RNA-seq samples for 15 species. 1/16

Importantly, our study was entirely designed around a symmetric #phylogeny for the vertebrate and insect branches, allowing us to identify ancestral features but also parallel, convergent and divergent evolutionary trajectories between and within the two bilaterian lineages. 2/16

Within this framework, we characterized tissue-specific expression in 7178 ancestral, broadly conserved bilaterian #orthogroups. We then investigated the extent, timings and mechanisms behind the evolution of these tissue-specific profiles, as well as their functional impact.3/16

We reconstructed strong cores of pan-bilaterian, tissue-specific genes enriched for relevant tissue functions, especially for neural, muscle and reproductive organs. Importantly, validated #phenotypes in mammals and in fly supported their extant physiological relevance. 4/16

However, these ancestral modules only comprised 7% of all bilaterian-conserved genes. We thus used the Tau metric to systematically characterize tissue-specific genes through the phylogeny. We identified hundreds of them, specially in neural and testis and among vertebrates. 5/16

Are these tissue-specific patterns conserved? The short answer is: largely not. For instance, for mouse tissue-specific orthogroups, only a median of 6/19 other species had orthologs with Tau ≥ 0.75 (and 9/19 for Tau ≥ 0.5). The same pattern held across all 20 species. 6/16

In fact, while only 4-15% of bilaterian-conserved orthogroups are tissue-specific in each species, >47% are tissue-specific in at least one species. In other words, half (!) of the ancestral bilaterian gene complement has acquired tissue-specific expression during evolution. 7/16

Given this pervasive evolutionary changes in gene expression, we performed a systematic phylogenetic inference of tissue-specificity gains and losses across the whole phylogeny. 8/16

Among many results, we found that the Vertebrata ancestor showed the highest number of gains. These gains involved a high fraction of 2R-ohnologs (paralogs from the vertebrate whole genome duplications [#WGD]), as expected from a boosting effect of these genomic events. 9/16

Strikingly, this #WGD effect seemed to extend beyond the Vertebrata ancestor, revealing an unappreciated prolonged effect of the WGDs on the evolution of tissue-specific expression across vertebrate ancestral nodes and extant species. 10/16

Moreover, the association between the gain of tissue-specificity and gene duplication applied to the entire phylogeny. For all nodes and extant species, orthogroups with inferred tissue-specificity had a higher proportion of duplicates than the corresponding background. 11/16

Also, we found evidence that the acquisition of tissue-specific expression occurred through the process of #specialization, where the specialized #paralog reduces its expression in most tissues, while the other paralog(s) conserve the ancestral broader expression pattern. 12/16

What about the functional implications of these patterns? We found GO categories that recurrently evolved tissue-specificity, while others did so only in specific nodes/species and in some cases could be linked to the emergence of novel phenotypic traits. 13/16

Strikingly, we also found that species-specific gains of tissue-specific expression were enriched among genes involved in cell-cell signaling, tissue #development and several other morphogenesis-related or developmental categories. 14/16

One remarkable such case is #FGF17, which was co-opted in the adult brain only in humans. Suggestively, it has been shown that Fgf17 enhances proliferation of oligodendrocyte progenitors and, when injected into aged mice, slows down brain aging and improves memory functions.15/16

In summary, our results shed light into the tissue-specific expression patterns of deeply conserved genes, showing that they are unexpectedly plastic. 🔎Check out the manuscript for many other results and analyses! 16/16

Thanks to @doctor_calvo, Yamile Marquez, Jon Permanyer, @antonio_torm, Josefa Cruz, Xavier Franch, F. Tulenko, D. Burguera,@BERTRANDStphan8, Toby Doyle, M. Nouzova,@petecurr, Fernando Noriega, @HectorEscriva1, Ina Arnone, Carrie Albertin, @KoralWotton, @IsabelAlmudi, David Martin

And extra thanks to @ERC_Research @EMBO_YIP @CienciaGob @UPFbiomed and @icreacommunity for funding and support! @academia_joven