The evolutionary origins of the lysosome-related organelle sorting machinery reveal fundamental homology in post-endosome trafficking pathways
Bibliographic record
Abstract
Abstract The major organelles and pathways of the endomembrane system were in place by the time of the last eukaryotic common ancestor (LECA) (∼1.5 billion years ago) and their acquisition were defining milestones during the process of eukaryogenesis itself. Comparative cell biology and evolutionary analyses show multiple instances of homology in the protein machinery controlling distinct inter-organelle trafficking routes. Resolving these homologous relationships allows us to explore processes underlying the emergence of new cellular compartments, infer ancestral states pre-dating LECA, and can even provide insight into the process of eukaryogenesis itself. Here we undertake a molecular evolutionary analysis, including providing a transcriptome of the jakobid flagellate Reclinomonas americana, exploring the origins of the machinery responsible for the biogenesis of lysosome-related organelles, the so-called Biogenesis of Lysosome-related Organelle Complexes (BLOCs 1,2, and 3). This pathway has been studied only in animals and is not considered a feature of the basic eukaryotic cell plan. We show that this machinery, and by inference the corresponding sorting pathway, was likely in place prior to the divergence of eukaryotes and is found in a much more diverse array of eukaryotes than is currently assumed. As such, this sorting pathway is likely an underappreciated facet of broader eukaryotic cellular function. Moreover, we resolve multiple points of ancient homology between all three BLOCs and other post-endosomal retrograde trafficking machinery (BORC, CCZ1/MON1, and a newly identified relationship with HOPS/CORVET) offering a mechanistic and evolutionary unification of these trafficking pathways. Overall, this study provides a comprehensive account of the rise of the LRO biogenesis machinery from prokaryotic origins to current eukaryotic diversity, Asgard archaea to animals, integrating it into the larger mechanistic framework describing endomembrane evolution.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".