Spontaneous Reversions of an Evolutionary Trait Loss Reveal Regulators of a Small RNA That Controls Multicellular Development in Myxobacteria
Bibliographic record
Abstract
ABSTRACT Lost traits can reevolve, but the probability of trait reversion depends partly on a trait's genetic complexity. Myxobacterial fruiting body development is a complex trait controlled by the small RNA (sRNA) Pxr, which blocks development under conditions of nutrient abundance. In developmentally proficient strains of Myxococcus xanthus , starvation relaxes the inhibition by Pxr, thereby allowing development to proceed. In contrast, the lab-evolved strain OC does not develop because it fails to relay an early starvation signal that alleviates inhibition by Pxr. A descendant of OC, strain PX, previously reevolved developmental proficiency via a mutation in pxr that inactivates its function. A single-colony screen was used to test whether reversion of OC to developmental proficiency occurs only by mutation of pxr or might also occur through alternative regulatory loci. Five spontaneous mutants of OC that exhibited restored development were isolated, and all five showed defects in Pxr synthesis, structure, or processing, including one that incurred an eight-nucleotide deletion in pxr . Two mutations occurred in the σ 54 response regulator (RR) gene MXAN_1078 (named pxrR here), immediately upstream of pxr . PxrR was found to positively regulate pxr transcription, presumably via the σ 54 promoter of pxr . Two other mutations were identified in a histidine kinase (HK) gene ( MXAN_1077 ; named pxrK here) immediately upstream of pxrR . Evolutionarily, the rate of trait restoration documented in this study suggests that reversion of social defects in natural microbial populations may be common. Molecularly, these results suggest a mechanism by which the regulatory functions of an HK-RR two-component signaling system and an sRNA are integrated to control initiation of myxobacterial development. IMPORTANCE Many myxobacteria initiate a process of multicellular fruiting body development upon starvation, but key features of the regulatory network controlling the transition from growth to development remain obscure. Previous work with Myxococcus xanthus identified the first small RNA (sRNA) regulator (Pxr) known to serve as a gatekeeper in this life history transition, as it blocks development when nutrients are abundant. In the present study, a screen for spontaneous mutants of M. xanthus was developed that revealed a two-component system operon (encoding a histidine kinase and a σ 54 response regulator) associated with the production and processing of Pxr sRNA. This discovery broadens our knowledge of early developmental gene regulation and also represents an evolutionary integration of two-component signaling and sRNA gene regulation to control a bacterial social trait.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".