Unique phylogenetic distributions of the Ska and Dam1 complexes support functional analogy and suggest multiple parallel displacements of Ska by Dam1

Faithful chromosome segregation relies on kinetochores, the large protein complexes that connect chromatin to spindle microtubules. Although human and yeast kinetochores are largely homologous, they track microtubules with the unrelated protein complexes Ska (Ska-C, human) and Dam1 (Dam1-C, yeast). We here uncovered that Ska-C and Dam1-C are both widespread among eukaryotes, but in an exceptionally inversemanner, supporting their functional analogy. Within the complexes, all Ska-C and various Dam1-C subunits are ancient paralogs, showing that gene duplication shaped these complexes.Weexamined various evolutionary scenarios to explain the nearlymutually exclusive patterns of Ska-C andDam1-C in present-day species.Wepropose that Ska-C was present in the last eukaryotic commonancestor, that subsequently Dam1-C displaced Ska-C in an early fungus andwas horizontally transferred to diverse non-fungal lineages, displacing Ska-C in these lineages too

Mosaic origin of the eukaryotic kinetochore

The emergence of eukaryotes from ancient prokaryotic lineages embodied a remarkable increase in cellular complexity. While prokaryotes operate simple systems to connect DNA to the segregation machinery during cell division, eukaryotes use a highly complex protein assembly known as the kinetochore. Although conceptually similar, prokaryotic segregation systems and the eukaryotic kinetochore are not homologous. Here we investigate the origins of the kinetochore before the last eukaryotic common ancestor (LECA) using phylogenetic trees, sensitive profile-versus-profile homology detection, and structural comparisons of its protein components. We show that LECA’s kinetochore proteins share deep evolutionary histories with proteins involved in a few prokaryotic systems and a multitude of eukaryotic processes, including ubiquitination, transcription, and flagellar and vesicular transport systems. We find that gene duplications played a major role in shaping the kinetochore; more than half of LECA’s kinetochore proteins have other kinetochore proteins as closest homologs. Some of these have no detectable homology to any other eukaryotic protein, suggesting that they arose as kinetochore-specific folds before LECA. We propose that the primordial kinetochore evolved from proteins involved in various (pre)eukaryotic systems as well as evolutionarily novel folds, after which a subset duplicated to give rise to the complex kinetochore of LECA

Inferring the Evolutionary History of Your Favorite Protein : A Guide for Molecular Biologists

Comparative genomics has proven a fruitful approach to acquire many functional and evolutionary insights into core cellular processes. Here it is argued that in order to perform accurate and interesting comparative genomics, one first and foremost has to be able to recognize, postulate, and revise different evolutionary scenarios. After all, these studies lack a simple protocol, due to different proteins having different evolutionary dynamics and demanding different approaches. The authors here discuss this challenge from a practical (what are the observations?) and conceptual (how do these indicate a specific evolutionary scenario?) viewpoint, with the aim to guide investigators who want to analyze the evolution of their protein(s) of interest. By sharing how the authors draft, test, and update such a scenario and how it directs their investigations, the authors hope to illuminate how to execute molecular evolution studies and how to interpret them. Also see the video abstract here https://youtu.be/VCt3l2pbdbQ

Enhancing the water holding capacity of model meat analogues through marinade composition

Meat analogues can offer consumers a more sustainable alternative to meat. A successful meat analogue is characterized by a meat-like texture and high juiciness. Juiciness is related to the water holding capacity (WHC). To gain an understanding of how to control the WHC via external conditions, we investigate the effect of ionic strength and pH on water uptake. Model meat analogues were prepared in a Shear Cell and swollen in baths of known pH and ionic strength. The effect of bath composition on water uptake was determined experimentally, and simulated using Flory–Rehner theory. Experiments and simulations were in qualitative agreement. The results show that water uptake increases with an increasing difference between bath pH and the protein's iso-electric point (pI). At low ionic strengths, the internal pH is near the pI, resulting in reduced swelling. At high ionic strengths, the charge imbalance between gel and bath is limited, also resulting in reduced swelling. At intermediate ionic strengths, swelling increases with decreasing bath ionic strength. Cross-link density negatively relates to WHC and can be controlled via the addition of cross-linking and reducing agents. This work shows that by carefully choosing marinade pH and ionic strength, the WHC of meat analogues can be controlled. These advancements can help improve the sensory characteristics and yield of meat analogues and could enable the production of reduced-salt products.</p

Mosaic origin of the eukaryotic kinetochore

The emergence of eukaryotes from ancient prokaryotic lineages embodied a remarkable increase in cellular complexity. While prokaryotes operate simple systems to connect DNA to the segregation machinery during cell division, eukaryotes use a highly complex protein assembly known as the kinetochore. Although conceptually similar, prokaryotic segregation systems and the eukaryotic kinetochore are not homologous. Here we investigate the origins of the kinetochore before the last eukaryotic common ancestor (LECA) using phylogenetic trees, sensitive profile-versus-profile homology detection, and structural comparisons of its protein components. We show that LECA’s kinetochore proteins share deep evolutionary histories with proteins involved in a few prokaryotic systems and a multitude of eukaryotic processes, including ubiquitination, transcription, and flagellar and vesicular transport systems. We find that gene duplications played a major role in shaping the kinetochore; more than half of LECA’s kinetochore proteins have other kinetochore proteins as closest homologs. Some of these have no detectable homology to any other eukaryotic protein, suggesting that they arose as kinetochore-specific folds before LECA. We propose that the primordial kinetochore evolved from proteins involved in various (pre)eukaryotic systems as well as evolutionarily novel folds, after which a subset duplicated to give rise to the complex kinetochore of LECA

Timing the origin of eukaryotic cellular complexity with ancient duplications

Data de publicació electrònica: 26-10-2020Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications provide information on the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis. We find that gene duplications roughly doubled the proto-eukaryotic gene repertoire, with families inherited from the Asgard archaea-related host being duplicated most. By relatively timing events using phylogenetic distances, we inferred that duplications in cytoskeletal and membrane-trafficking families were among the earliest events, whereas most other families expanded predominantly after mitochondrial endosymbiosis. Altogether, we infer that the host that engulfed the proto-mitochondrion had some eukaryote-like complexity, which drastically increased upon mitochondrial acquisition. This scenario bridges the signs of complexity observed in Asgard archaeal genomes to the proposed role of mitochondria in triggering eukaryogenesis

Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment

We implicated the X-chromosome THOC2 gene, which encodes the largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically complex neurodevelopmental disorder with intellectual disability as the core phenotype. To study the molecular pathology of this essential eukaryotic gene, we generated a mouse model based on a hypomorphic Thoc2 exon 37–38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37–38 deletion male (Thoc2Δ/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2Δ/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.Rudrarup Bhattacharjee, Lachlan A. Jolly, Mark A. Corbett, Ing Chee Wee, Sushma R. Rao, Alison E. Gardner, Tarin Ritchie, Eline J. H. van Hugte, Ummi Ciptasari, Sandra Piltz, Jacqueline E. Noll, Nazzmer Nazri, ClareL. vanEyk, Melissa White, Dani Fornarino, Cathryn Poulton, Gareth Baynam, Lyndsey E.Collins-Praino, MartenF. Snel, Nael Nadif Kasri, Kim M.Hemsley, Paul Q. Thomas, Raman Kumar, Jozef Gec