Genetics

TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells

1. Dharmendra Kumar Nath
2. Subash Dhakal
3. Youngseok Lee

• Curated by eLife

  eLife Assessment

  This important study reports findings that Trpγ, a type of transient receptor potential (TRP) channel expressed in Dh44-releasing neuroendocrine cells, mediates starvation-dependent lipid catabolism. Overall, the claims of the authors are supported by solid evidence. The work should be of interest to both basic and medical biologists working on lipid metabolism.

Reviewed by eLife

Functional characterization of all CDKN2A missense variants and comparison to in silico models of pathogenicity

1. Hirokazu Kimura
2. Kamel Lahouel
3. Cristian Tomasetti
4. Nicholas Jason Roberts

• Curated by eLife

  eLife Assessment

  This is a saturation mutagenesis screening of CDKN2A gene, successfully assessing the functionality of the missense variants. The work is solid and well-prosecuted. The manuscript was improved during the revision process and this work will serve as a valuable resource for diagnostic labs as well as cancer geneticists.

Reviewed by eLife

Molecular requirements for C. elegans transgenerational epigenetic inheritance of pathogen avoidance

1. Rachel Kaletsky
2. Rebecca S Moore
3. Titas Sengupta
4. Renee Seto
5. Borja Ceballos-Llera
6. Coleen T Murphy

• Curated by eLife

  eLife Assessment

  This fundamental study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. The authors test the impact of procedural alterations made in another study, by Gainey et al., which claimed that transgenerational inheritance in this paradigm lacks robustness, despite this observation having been reported in multiple papers from the Murphy lab. The authors of the present study show that by following a non-standard avoidance protocol, Gainey et al. likely biased their measurements in a way that made it hard to observe learned avoidance. The authors also highlight the importance of bacterial growth conditions, showing that expression of the trigger molecule, the bacterial P11 RNA, which is necessary and sufficient to drive the transgenerational inheritance of the avoidance phenotype, is influenced by temperature. As expression of P11 was not verified by Gainey et al., this provides another explanation for the inability to observe transgenerational epigenetic inheritance. Together, the authors provide compelling and powerful arguments that the original phenomenon is robust and that it can be reproduced in the Murphy lab by following their original protocol precisely, including the use of azide to immobilize the worms at the food source. Overall, this study not only provides guidance for investigators in this experimental paradigm, but it also provides additional understanding of the differences between naïve preference, learned preference, and transgenerational epigenetic inheritance. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

Reviewed by eLife

Diverse Genotype-by-Weather Interactions in Switchgrass

1. Alice H MacQueen
2. Li Zhang
3. Samuel Pattillo Smith
4. Jason E Bonnette
5. Arvid R Boe
6. Philip A Fay
7. Felix B Fritschi
8. David B Lowry
9. Robert B Mitchell
10. Francis M Rouquette
11. Yanqi Wu
12. Arbel Harpak
13. Thomas E Juenger

• Curated by eLife

  eLife Assessment

  The study reports valuable findings on the nature of genotype-by-climate interaction, parameterised in a framework that allows integrating genetics and ecophysiological variation in switchgrass. The evidence provided is solid overall but the analysis could be improved to better support some of the claims.

Reviewed by eLife

A mathematical model that predicts human biological age from physiological traits identifies environmental and genetic factors that influence aging

1. Sergiy Libert
2. Alex Chekholko
3. Cynthia Kenyon

• Curated by eLife

  eLife Assessment

  This important study developed a mathematical model to predict biological age by leveraging physiological traits across multiple organ systems. The results presented are convincing, utilizing comprehensive data-driven approaches. However, additional external validation could further strengthen its generalizability. The model provides a way to identify environmental and genetic factors impacting aging and lifespan, revealing new factors potentially affecting aging. It also shows promise for evaluating therapeutics aimed at prolonging a healthy lifespan.

Reviewed by eLife

DNA replication in primary hepatocytes without the six-subunit ORC

1. Róża K Przanowska
2. Yuechuan Chen
3. Takayuki-Okano Uchida
4. Etsuko Shibata
5. Xiaoxiao Hao
6. Isaac Segura Rueda
7. Kate Jensen
8. Piotr Przanowski
9. Anthony Trimboli
10. Yoshiyuki Shibata
11. Gustavo Leone
12. Anindya Dutta

• Curated by eLife

  eLife Assessment

  This valuable descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors obtain solid data using various methods to genetically remove one or two ORC subunits from specific tissues and still observe replication. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. The mechanism behind this ORC-independent replication remains to be elucidated. The study and mutants described herein lay the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers suggested the observations could be supported by additional experiments. This work will be of interest to those studying genome duplication and replication.

Reviewed by eLife, Review Commons

Proteostasis modulates gene dosage evolution in antibiotic-resistant bacteria

1. Chinmaya Jena
2. Saillesh Chinnaraj
3. Soham Deolankar
4. Nishad Matange

• Curated by eLife

  eLife Assessment

  This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide compelling evidence connecting proteostasis with gene duplication during experimental evolution in a model system. This paper is likely to be of interest to researchers studying antibiotic resistance, proteostasis, and bacterial evolution.

Reviewed by eLife

Neanderthal-derived variants shape craniofacial enhancer activity at a human disease locus

1. Kirsty Uttley
2. Hannah J Jüllig
3. Carlo De Angelis
4. Julia MT Auer
5. Ewa Ozga
6. Hemant Bengani
7. Hannah K Long

Reviewed by Review Commons

A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity

1. Sreesankar Easwaran
2. Denise J Montell

• Curated by eLife

  eLife Assessment

  This important study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are convincing, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

Reviewed by eLife

UBR-1 deficiency leads to ivermectin resistance in Caenorhabditis elegans

1. Yi Li
2. Long Gong
3. Jing Wu
4. Wesley Hung
5. Mei Zhen
6. Shangbang Gao

• Curated by eLife

  eLife Assessment

  This important study allows for a better understanding of anthelmintic drug resistance in nematodes. The authors provide a detailed analysis of the role of UBR-1 and its underlying mechanism in ivermectin resistance using convincing behavioural and genetic experiments with C. elegans. Although the authors have addressed the concerns of the reviewers, it would be prudent for the authors to disclose the Dyf phenotype in ubr-1 mutants. The authors should at the very least report the Dyf phenotype and the experiment on which they base the argument that the Dyf phenotype does not affect their conclusions.

Reviewed by eLife