Search

In addition to known genes, much of the human genome is transcribed into RNA. Chance formation of novel open reading frames (ORFs) can lead to the translation of myriad new proteins. Some of these ORFs may yield advantageous adaptive de novo proteins. However, widespread translation of noncoding DNA can also produce hazardous protein molecules, which can misfold and/or form toxic aggregates. The dynamics of how de novo proteins emerge from potentially toxic raw materials and what influences their long-term survival are unknown. Here, using transcriptomic data from human and five other primates, we generate a set of transcribed human ORFs at six conservation levels to investigate which properties influence the early emergence and long-term retention of these expressed ORFs. As these taxa diverged from each other relatively recently, we present a fine scale view of the evolution of novel sequences over recent evolutionary time. We find that novel human-restricted ORFs are preferentially located on GC-rich gene-dense chromosomes, suggesting their retention is linked to pre-existing genes. Sequence properties such as intrinsic structural disorder and aggregation propensity—which have been proposed to play a role in survival of de novo genes—remain unchanged over time. Even very young sequences code for proteins with low aggregation propensities, suggesting that genomic regions with many novel transcribed ORFs are concomitantly less likely to produce ORFs which code for harmful toxic proteins. Our data indicate that the survival of these novel ORFs is largely stochastic rather than shaped by selection.

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called ‘selection shadow’, due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant, Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in old C. obscurior queens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.Significance StatementUnderstanding the exceptional longevity of ant queens and how they defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory and molecular biology of ageing. In this study we offer several clues as to how this occurs on a molecular level in C. obscurior queens. Specifically, we believe a reduction in the selection shadow due to low extrinsic mortality, has allowed the evolution of well-regulated anti-ageing mechanisms. Consequently, we suggest several promising starting points for future research into the poorly understood phenomenon of extreme longevity in ant queens. Making progress in this field will not only allow us to better understand longevity and fertility in social insects but may also offer interesting research strategies for human ageing.

Transcriptional regulation is crucial for all biological processes and well investigated at the molecular level for a wide range of organisms. However, it is quite unclear how innovations, such as the activity of a novel regulatory element, evolve. In the case of transcription factor (TF) binding, both a novel TF and a novel-binding site would need to evolve concertedly. Since promiscuous functions have recently been identified as important intermediate steps in creating novel specific functions in many areas such as enzyme evolution and protein–protein interactions, we ask here how promiscuous binding of TFs to TF-binding sites (TFBSs) affects the robustness and evolvability of this tightly regulated system. Specifically, we investigate the binding behavior of several hundred TFs from different species at unprecedented breadth. Our results illustrate multiple aspects of TF-binding interactions, ranging from correlations between the strength of the interaction bond and specificity, to preferences regarding TFBS nucleotide composition in relation to both domains and binding specificity. We identified a subset of high A/T binding motifs. Motifs in this subset had many functionally neutral one-error mutants, and were bound by multiple different binding domains. Our results indicate that, especially for some TF–TFBS associations, low binding specificity confers high degrees of evolvability, that is that few mutations facilitate rapid changes in transcriptional regulation, in particular for large and old TF families. In this study we identify binding motifs exhibiting behavior indicating high evolutionary potential for innovations in transcriptional regulation.

Orphan genes are defined as genes that lack detectable similarity to genes in other species and therefore no clear signals of common descent (i.e., homology) can be inferred. Orphans are an enigmatic portion of the genome because their origin and function are mostly unknown and they typically make up 10% to 30% of all genes in a genome. Several case studies demonstrated that orphans can contribute to lineage-specific adaptation. Here, we study orphan genes by comparing 30 arthropod genomes, focusing in particular on seven recently sequenced ant genomes. This setup allows analyzing a major metazoan taxon and a comparison between social Hymenoptera (ants and bees) and nonsocial Diptera (flies and mosquitoes). First, we find that recently split lineages undergo accelerated genomic reorganization, including the rapid gain of many orphan genes. Second, between the two insect orders Hymenoptera and Diptera, orphan genes are more abundant and emerge more rapidly in Hymenoptera, in particular, in leaf-cutter ants. With respect to intragenomic localization, we find that ant orphan genes show little clustering, which suggests that orphan genes in ants are scattered uniformly over the genome and between nonorphan genes. Finally, our results indicate that the genetic mechanisms creating orphan genes—such as gene duplication, frame-shift fixation, creation of overlapping genes, horizontal gene transfer, and exaptation of transposable elements—act at different rates in insects, primates, and plants. In Formicidae, the majority of orphan genes has their origin in intergenic regions, pointing to a high rate of de novo gene formation or generalized gene loss, and support a recently proposed dynamic model of frequent gene birth and death.

Plant genomes are generally very large, mostly paleopolyploid, and have numerous gene duplicates and complex genomic features such as repeats and transposable elements. Many of these features have been hypothesized to enable plants, which cannot easily escape environmental challenges, to rapidly adapt. Another mechanism, which has recently been well described as a major facilitator of rapid adaptation in bacteria, animals, and fungi but not yet for plants, is modular rearrangement of protein-coding genes. Due to the high precision of profile-based methods, rearrangements can be well captured at the protein level by characterizing the emergence, loss, and rearrangements of protein domains, their structural, functional, and evolutionary building blocks. Here, we study the dynamics of domain rearrangements and explore their adaptive benefit in 27 plant and 3 algal genomes. We use a phylogenomic approach by which we can explain the formation of 88% of all arrangements by single-step events, such as fusion, fission, and terminal loss of domains. We find many domains are lost along every lineage, but at least 500 domains are novel, that is, they are unique to green plants and emerged more or less recently. These novel domains duplicate and rearrange more readily within their genomes than ancient domains and are overproportionally involved in stress response and developmental innovations. Novel domains more often affect regulatory proteins and show a higher degree of structural disorder than ancient domains. Whereas a relatively large and well-conserved core set of single-domain proteins exists, long multi-domain arrangements tend to be species-specific. We find that duplicated genes are more often involved in rearrangements. Although fission events typically impact metabolic proteins, fusion events often create new signaling proteins essential for environmental sensing. Taken together, the high volatility of single domains and complex arrangements in plant genomes demonstrate the importance of modularity for environmental adaptability of plants.

Mechanoreception, the sensing of mechanical forces, is an ancient means of orientation and communication and tightly linked to the evolution of motile animals. In flies, the transient-receptor-potential N protein (TRP-N) was found to be a cilia-associated mechanoreceptor. TRP-N belongs to a large and diverse family of ion channels. Its unusually long N-terminal repeat of 28 ankyrin domains presumably acts as the gating spring by which mechanical energy induces channel gating. We analyzed the evolutionary origins and possible diversification of TRP-N. Using a custom-made set of highly discriminative sequence profiles we scanned a representative set of metazoan genomes and subsequently corrected several gene models. We find that, contrary to other ion channel families, TRP-N is remarkably conserved in its domain arrangements and copy number (1) in all Bilateria except for amniotes, even in the wake of several whole-genome duplications. TRP-N is absent in Porifera but present in Ctenophora and Placozoa. Exceptional multiplications of TRP-N occurred in Cnidaria, independently along the Hydra and the Nematostella lineage. Molecular signals of subfunctionalization can be attributed to different mechanisms of activation of the gating spring. In Hydra this is further supported by in situ hybridization and immune staining, suggesting that at least three paralogs adapted to nematocyte discharge, which is key for predation and defense. We propose that these new candidate proteins help explain the sensory complexity of Cnidaria which has been previously observed but so far has lacked a molecular underpinning. Also, the ancient appearance of TRP-N supports a common origin of important components of the nervous systems in Ctenophores, Cnidaria, and Bilateria.