Genetics

A moonlighting function of a chitin polysaccharide monooxygenase, CWR-1, in Neurospora crassa allorecognition

1. Tyler C Detomasi
2. Adriana M Rico-Ramírez
3. Richard I Sayler
4. A Pedro Gonçalves
5. Michael A Marletta
6. N Louise Glass

• Curated by eLife

  Evaluation Summary:

  This study identifies an important role for a lytic polysaccharide monooxygenase in allorecognition in the filamentous fungus Neurospora crassa, which is independent of the catalytic activity of this remarkable class of proteins. The study's findings are strongly supported through an interdisciplinary approach, combining microscopy with genetics and biochemistry. The study will be of great interest to fungal biologists and microbiologists, as well as biochemists studying carbohydrate-active enzymes.

  (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

Limitations of principal components in quantitative genetic association models for human studies

1. Yiqi Yao
2. Alejandro Ochoa

• Curated by eLife

  Evaluation Summary:

  This simulation study is of interest to geneticists, especially those carrying out Genome-wide Association Studies (GWAS). It compares two major approaches for dealing with "population structure"in GWAS: Principal Component Analysis (PCA) and Linear Mixed-effects Models (LMMs). This is a subject of considerable practical importance and the study nicely reviews the theoretical underpinnings and concludes - based on the review and the extensive simulations - that there is every reason to believe LMMs to be superior (although PCA is more widely used). Although this point has been made before, it is worth making again given the ubiquity of these analyses. There are some concerns about the general validity of the claim given that the simulations fail to address several real-world problems.

  (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.)

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The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters

1. Lisa Baumgartner
2. Dominik Handler
3. Sebastian Wolfgang Platzer
4. Changwei Yu
5. Peter Duchek
6. Julius Brennecke

• Curated by eLife

  Evaluation Summary:

  Interactions between transposons and the Drosophila host genome are governed by dedicated H3K9me3-enriched loci that are selected for producing anti-transposon piRNAs through binding by the HP1 variant Rhino in Drosophila. The authors identify Kipferl, a ZAD zinc-finger protein, as helping to guide Rhino to G-rich motifs found at piRNA-producing loci in the female germline. The work thus reveals the involvement of a factor binding specific DNA sequences in piRNA biogenesis. The findings are of broad interest to the fields of heterochromatin and transposon biology.

  (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

Genetic architecture of natural variation of cardiac performance from flies to humans

1. Saswati Saha
2. Lionel Spinelli
3. Jaime A Castro Mondragon
4. Anaïs Kervadec
5. Michaela Lynott
6. Laurent Kremmer
7. Laurence Roder
8. Sallouha Krifa
9. Magali Torres
10. Christine Brun
11. Georg Vogler
12. Rolf Bodmer
13. Alexandre R Colas
14. Karen Ocorr
15. Laurent Perrin

Reviewed by Review Commons

MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size

1. Michael J Lafferty
2. Nil Aygün
3. Niyanta K Patel
4. Oleh Krupa
5. Dan Liang
6. Justin M Wolter
7. Daniel H Geschwind
8. Luis de la Torre-Ubieta
9. Jason L Stein

• Curated by eLife

  Evaluation Summary:

  This paper is one of the first demonstrations that expression quantitative trait loci (eQTL) affecting human microRNAs are linked to brain development affecting brain structure and function. These findings will have a broad impact on the genomics, neural development, and microRNA fields. The datasets produced here (developmental changes in miRNAs, new human miRNAs) will likely be used for further discoveries. However, some claims need to be tempered.

  (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.)

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Real time, in vivo measurement of neuronal and peripheral clocks in Drosophila melanogaster

1. Peter S Johnstone
2. Maite Ogueta
3. Olga Akay
4. Inan Top
5. Sheyum Syed
6. Ralf Stanewsky
7. Deniz Top

• Curated by eLife

  Evaluation Summary:

  This paper presents a novel and potentially highly useful approach to monitor circadian rhythms in specific tissues. The elegant reporter that the authors have built has the potential to become an important tool for understanding how different body clocks respond to various inputs and genetic manipulations. The authors already apply it to show that different clocks appear to be responding differently to loss of signaling from a key circadian neuropeptide in Drosophila melanogaster. However, it is difficult to determine whether these results, as currently presented and analyzed, provide new insight into the relationship between brain and peripheral clocks. The work is of interest to the community of biologists studying biological rhythms.

  (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

Using adopted individuals to partition indirect maternal genetic effects into prenatal and postnatal effects on offspring phenotypes

1. Liang-Dar Hwang
2. Gunn-Helen Moen
3. David M Evans

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to scientists interested in intergenerational transmission of phenotypes through genetic pathways. The authors propose an innovative and sound method to leverage the adoption of a design for disentangling prenatal and postnatal genetic effects. Additional analyses are needed to address the limitations of the model applied to the specific dataset that was used to illustrate the method.

  (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.)

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Diet’s impact dictated by synonymous mitochondrial SNP interacting with nucleotype

1. Adam J. Dobson
2. Susanne Voigt
3. Luisa Kumpitsch
4. Lucas Langer
5. Emmely Voigt
6. Rita Ibrahim
7. Damian K. Dowling
8. Klaus Reinhardt

Reviewed by Review Commons

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