Genetics

Genome-wide base editor screen identifies regulators of protein abundance in yeast

1. Olga T Schubert
2. Joshua S Bloom
3. Meru J Sadhu
4. Leonid Kruglyak

• Curated by eLife

  Evaluation Summary:

  Schubert and coworkers report the development of a novel CRISPR-based screening method that allows probing interactions between (a large set of) specific mutations and the abundance of specific proteins, and, more generally, investigate the spectrum of effects that (point) mutations can have on protein abundance. This complements existing strategies for measuring effects of genetic perturbations on transcript levels, which is important as for some proteins mRNA and protein levels do not correlate well. The ability to measure proteins directly therefore promises to close an important gap in our understanding of the links between genotype and phenotype, and the strategy is broadly applicable beyond the current study.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination

1. Oguz Kanca
2. Jonathan Zirin
3. Yanhui Hu
4. Burak Tepe
5. Debdeep Dutta
6. Wen-Wen Lin
7. Liwen Ma
8. Ming Ge
9. Zhongyuan Zuo
10. Lu-Ping Liu
11. Robert W Levis
12. Norbert Perrimon
13. Hugo J Bellen

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of general interest to Drosophila researchers, whose work has long relied on the tools generated by the Gene Disruption Project (GDP). This manuscript provides a notable update on the work of the GDP. In it, the authors demonstrate the efficacy of new, streamlined transformation vectors, which they use to generate several hundred novel gene-specific Gal4 driver lines using CRISPR technology. The new vectors promise to allow the GDP to complete its goal of creating null mutations for every gene in the fly genome. The elegant functionality of the new vectors will also likely be of interest to workers outside of Drosophila.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors

1. Minsu Kang
2. Hee Young Na
3. Soomin Ahn
4. Ji-Won Kim
5. Sejoon Lee
6. Soyeon Ahn
7. Ju Hyun Lee
8. Jeonghwan Youk
9. Haesook T Kim
10. Kui-Jin Kim
11. Koung Jin Suh
12. Jun Suh Lee
13. Se Hyun Kim
14. Jin Won Kim
15. Yu Jung Kim
16. Keun-Wook Lee
17. Yoo-Seok Yoon
18. Jee Hyun Kim
19. Jin-Haeng Chung
20. Ho-Seong Han
21. Jong Seok Lee

• Curated by eLife

  Evaluation Summary:

  The authors collected human samples from a rare cancer type in which evolutionary features have not been well-defined. They describe the clonal evolution through sampling at precancerous, primary tumour, and metastatic stages. Whole exome sequencing was performed and one of the mutation types was confirmed with other techniques.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs

1. Nicholas O Burton
2. Alexandra Willis
3. Kinsey Fisher
4. Fabian Braukmann
5. Jonathan Price
6. Lewis Stevens
7. L Ryan Baugh
8. Aaron Reinke
9. Eric A Miska

• Curated by eLife

  Evaluation Summary:

  The authors study intergenerational adaptation patterns in four relatively closely related nematode species, using previously established experimental procedures. Phenotypic and transcriptomic data are used to compare responses to stress triggers in the offspring generation between the species. The authors conclude that at least some of the responses are evolutionary conserved.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Unbiased mosaic variant assessment in sperm: a cohort study to test predictability of transmission

1. Martin W Breuss
2. Xiaoxu Yang
3. Valentina Stanley
4. Jennifer McEvoy-Venneri
5. Xin Xu
6. Arlene J Morales
7. Joseph G Gleeson

• Curated by eLife

  Evaluation Summary:

  This manuscript analyzes human blastocysts from in vitro fertilization for three subjects (a total of 55 blastocysts), demonstrating transmission of mosaic mutations at close to expected frequencies. These studies are the first of their kind and of translational relevance for the field of clinical genetics and prenatal genetic testing, with the potential to contribute to strategies to reduce genetic disease risk in future offspring.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Variable paralog expression underlies phenotype variation

1. Raisa Bailon-Zambrano
2. Juliana Sucharov
3. Abigail Mumme-Monheit
4. Matthew Murry
5. Amanda Stenzel
6. Anthony T Pulvino
7. Jennyfer M Mitchell
8. Kathryn L Colborn
9. James T Nichols

• Curated by eLife

  Evaluation Summary:

  In this elegant genetic study, Bailon-Zambrano and colleagues draw on classical genetic concepts to address the clinically pertinent question of how genetic variants in the same gene can yield wildly different phenotypes in different individuals. From their case study they conclude that a major contributor is variation in paralog expression. The question addressed is of great interest to evolutionary and developmental biologists in general and to those studying the evolution of developmental mechanisms in particular.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)

Reviewed by eLife

Conditional GWAS of non-CG transposon methylation in Arabidopsis thaliana reveals major polymorphisms in five genes

1. Eriko Sasaki
2. Joanna Gunis
3. Ilka Reichardt-Gomez
4. Viktoria Nizhynska
5. Magnus Nordborg

Reviewed by Review Commons

The ACF chromatin-remodeling complex is essential for Polycomb repression

1. Elizabeth T Wiles
2. Colleen C Mumford
3. Kevin J McNaught
4. Hideki Tanizawa
5. Eric U Selker

• Curated by eLife

  Evaluation Summary:

  The chromatin mark, H3K27me, is deposited by the Polycomb complex PRC2 and is associated with repressed genes. There are two important findings in this paper: 1) that the promoters of some H3K27me-repressed genes are regulated by nucleosome positioning and 2) the H3K27me repressed genes are a diverse group that can be derepressed by different mechanisms.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons

1. Lewis Macdonald
2. Gillian C Taylor
3. Jennifer Margaret Brisbane
4. Ersi Christodoulou
5. Lucy Scott
6. Alex von Kriegsheim
7. Janet Rossant
8. Bin Gu
9. Andrew J Wood

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to the broad class of biologists and especially mouse geneticists who study the function of protein-coding genes. The authors confirm the utility of the auxin-inducible degron tool to rapidly degrade the target protein of interest by developing genetically modified mouse models. This expands the set of tools to study gene function in a cell/tissue type, in adults (bypassing embryonic lethality) and also to more finely dissect the different functions of pleiotropic genes.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Functional evolution of SARS-COV-2 Spike protein: adaptation on translation and infection via surface charge of spike protein

1. Xiaolong Lu
2. Gong Zhang

Reviewed by ScreenIT