Genetics

H3K9me1/2 methylation limits the lifespan of daf-2 mutants in C. elegans

1. Meng Huang
2. Minjie Hong
3. Xinhao Hou
4. Chengming Zhu
5. Di Chen
6. Xiangyang Chen
7. Shouhong Guang
8. Xuezhu Feng

• Curated by eLife

  Evaluation Summary:

  This manuscript examines how putative C. elegans H3K9me methyltransferases affect aging by investigating their effects on long-lived daf-2 mutants. They surprisingly find that modifiers of H3K9me1/2, but not H3K9me3, can synergistically extend the lifespan of daf-2 (in some cases, to three times as long as wild-type). They demonstrate that this synergistic effect on lifespan requires the DAF-16 transcription factor and some of its downstream regulatory targets, and compellingly, they show that the effects on lifespan are phenocopied by a small molecular inhibitor known to target a conserved H3K9me1/2 HMT.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Closely related type II-C Cas9 orthologs recognize diverse PAMs

1. Jingjing Wei
2. Linghui Hou
3. Jingtong Liu
4. Ziwen Wang
5. Siqi Gao
6. Tao Qi
7. Song Gao
8. Shuna Sun
9. Yongming Wang

• Curated by eLife

  Evaluation Summary:

  This work is relevant to all who are interested in genome editing. The versatile Cas9 nuclease has enabled creative genome editing applications, yet the targetable sequence space is limited by the PAM specificity of the Cas9 RNP. This manuscript expands the Cas9 toolbox by defining the PAM specificity and genome editing activity of a large group of smaller-sized type II-C Cas9s. The results also contribute to our understanding of the diversity of Cas enzymes and show that there is a significant potential in mining for non-trivial genome editing tools amongst highly similar Cas orthologs.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Schizosaccharomyces pombe Rtf2 is important for replication fork barrier activity of RTS1 via splicing of Rtf1

1. Alice M Budden
2. Murat Eravci
3. Adam T Watson
4. Eduard Campillo-Funollet
5. Antony W Oliver
6. Karel Naiman
7. Antony M Carr

• Curated by eLife

  Evaluation Summary:

  DNA replication forks can become arrested either in a cellular program or by accident. In fission yeast, DNA replication fork arrests at the locus called the RTS1 are mediated by a DNA binding protein, Rtf1. In this paper, by combining genetics, proteomics, and genomics approaches, the authors nicely showed the role of Rtf2 as a fork barrier to mediate the splicing of rtf1 mRNA. The splicing-mediated control of protein abundance provides a new regulatory mechanism for the programmed DNA replication barrier.

  (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 names with the authors.)

Reviewed by eLife

A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene

1. Yonghe Ding
2. Di Lang
3. Jianhua Yan
4. Haisong Bu
5. Hongsong Li
6. Kunli Jiao
7. Jingchun Yang
8. Haibo Ni
9. Stefano Morotti
10. Tai Le
11. Karl J Clark
12. Jenna Port
13. Stephen C Ekker
14. Hung Cao
15. Yuji Zhang
16. Jun Wang
17. Eleonora Grandi
18. Zhiqiang Li
19. Yongyong Shi
20. Yigang Li
21. Alexey V Glukhov
22. Xiaolei Xu

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest to cardiovascular and developmental biologists as it describes Dnajb6 as a novel gene linked with Sick Sinus Syndrome. The claims are mostly supported by observations using zebrafish dnajb6b trap line and Dnajb6 heterozygous mouse models. However, the paper would be strengthened be clarification of some experimental aspects and a discussion of the potential connection of DNAJB6 to the Sick Sinus Syndrome in humans.

  (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

Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice

1. Shauni Doms
2. Hanna Fokt
3. Malte Christoph Rühlemann
4. Cecilia J Chung
5. Axel Kuenstner
6. Saleh M Ibrahim
7. Andre Franke
8. Leslie M Turner
9. John F Baines

• Curated by eLife

  Evaluation Summary:

  The paper uses hybrid mouse lines to estimate the heritability of the microbiome and map variants in the mouse genome that are associated with the composition of the microbiome. The findings are of broad interest to microbiome researchers and improve on knowledge in the field, as they focus on mucosa-associated (rather than fecal) microbiome profiles and report a novel correlation between heritability and cospeciation rates. The results are intriguing, but technical and biological confounders are incompletely addressed in the manuscript's present form, potentially leading to surprisingly high estimates of microbiome trait heritability relative to previous work.

  (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

Surface detection of SARS-CoV-2 by lateral flow LAMP

1. Isabelle Dahl Acker
2. Mark Joseph Ware
3. John Russell Bracht

Reviewed by ScreenIT

Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs

1. Antonio Cuevas-Navarro
2. Laura Rodriguez-Muñoz
3. Joaquim Grego-Bessa
4. Alice Cheng
5. Katherine A Rauen
6. Anatoly Urisman
7. Frank McCormick
8. Gerardo Jimenez
9. Pau Castel

• Curated by eLife

  Evaluation Summary:

  This is a very elegant study that through cross-species analysis describes the evolution of ubiquitin ligase adaptor protein LZTR1-mediated degradation of RAS-related GTPase RIT1 as a principal regulatory mechanism for RIT1 function and its role in Noonan syndrome, a prominent subgroup of RASopathy disorders. Extensive genetic experiments in Drosophila and mouse suggest that important pathological phenotypes observed in LZTR1-linked RASopathy models are mediated by its ubiquitination target RIT1 and less by the canonical RAS isoforms. While the work further supports the connection between LZTR1 mediated RIT1 level modulation, it does not fully rule out the significance of canonical RAS isoforms in LZTR1-associated RASopathies in humans.

  (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 #3 agreed to share their names with the authors.)

Reviewed by eLife

Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population

1. Khai C Ang
2. Victor A Canfield
3. Tiffany C Foster
4. Thaddeus D Harbaugh
5. Kathryn A Early
6. Rachel L Harter
7. Katherine P Reid
8. Shou Ling Leong
9. Yuka Kawasawa
10. Dajiang Liu
11. John W Hawley
12. Keith C Cheng

• Curated by eLife

  Evaluation Summary:

  The work reports collection of DNA from 400-plus individuals from the Kalinago territory of Dominica, and shows their relationships with other ancestries, along with a more specific genetic analysis of skin pigmentation. The material is clearly rare and hard to obtain and the analyses are extremely interesting. The work will be of interest to all studying human populations.

  (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

Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population

1. Yiran Shen
2. Bhuwan Khatri
3. Santosh Rananaware
4. Danmeng Li
5. David A. Ostrov
6. Piyush K Jain
7. Christopher J. Lessard
8. Cuong Q. Nguyen

Reviewed by ScreenIT

Barcoded bulk QTL mapping reveals highly polygenic and epistatic architecture of complex traits in yeast

1. Alex N Nguyen Ba
2. Katherine R Lawrence
3. Artur Rego-Costa
4. Shreyas Gopalakrishnan
5. Daniel Temko
6. Franziska Michor
7. Michael M Desai

• Curated by eLife

  Evaluation Summary:

  Overall, this is an impressive and interesting piece of work that not only expands the identification of small-effect QTL, but also reveals epistatic interactions at an unprecedented scale. Their approach takes advantage of DNA barcodes to increase the scale of genetic mapping studies in yeast by an order of magnitude over previous studies, yielding a more complete and precise view of the QTL landscape and confirming widespread epistatic interactions between the different QTL.

  (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