Genetics and Genomics

eLife assessment

This important study offers new and convincing support for the idea that about a third of mouse liver DNAse hypersensitivity sites (DHS) showing male-biased chromatin opening are sex-biased because of the male-specific cyclic action of growth hormone pulses to alter chromatin accessibility, as compared to the relative ineffectiveness of the more static pattern of growth hormone secretion in females. Supporting evidence is found in the impact of hypophysectomy and growth hormone treatment on chromatin accessibility, and the binding of specific transcription factors and epigenetic marks at STAT5-sensitive sites. This work uncovers mechanisms underlying sex differences in liver function and will be of broad interest to endocrinologists and hepatologists.

eLife assessment

This useful study reports an investigation of ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mice, providing a model of myopia. The evidence supporting the conclusions is currently incomplete. It could be strengthened by a more thorough genetic analysis, fuller presentation of human phenotypic data, and more explanation for the reasons why there was no increased axial length in mice with myopia. The work will be of interest to ophthalmologists and researchers working on myopia.

eLife assessment

This valuable paper examines the Bithorax complex in several butterfly species, in which the complex is contiguous and not split, as it is in the well-studied fruit fly Drosophila. Based on genetic screens and genetic manipulations of a boundary element involved in segment-specific regulation of Ubx, the authors provide convincing evidence for their conclusions, which could be strengthened by additional data and analyses in the future. The data presented are relevant for those interested in the evolution and function of Hox genes and of gene regulation in general.

eLife assessment

This important study advances our understanding of the biological significance of the DNA sequence adjacent to telomeres. The data presented convincingly demonstrate that subtelomeric repeats are non-essential and have a minimal, if any, role in maintaining telomere integrity of budding yeast. The work will be of interest to the telomere community specifically and the genome integrity community more broadly.

eLife assessment

This paper will be of considerable interest to population geneticists and other scholars in the field of paleogenomics. The study provides an impressive dataset containing 200+ novel human ancient genome sequences and a very creative, robust, and novel approach for studying human migration across time using ancient DNA. The authors find that the population structure in Europe has been remarkably stable over time. The conclusions are well supported by the data and the methods used are thoughtful and rigorous.

eLife assessment

This important work combines DNA contact analysis and controlled genome rearrangements to investigate the processes that organize the E. coli chromosome, with a particular focus on how the SMC-related complex MukBEF is regulated. The evidence supporting the conclusions is compelling, with time-resolved experiments and analysis of mutant strains. The work will be of broad interest to chromosome biologists and bacterial cell biologists.

eLife assessment

This valuable study analyzes a large cohort of Adolescent Idiopathic Scoliosis (AIS) patients, identifying an association with a variant in COL11A1 (Pro1335Leu). Experimental testing of this potentially pathogenic variant in vitro suggests a connection between Pax1, Col11a1, Mmp3, and estrogen signaling, thus providing solid support for the proposed link between hormonal and matrix components in the development of AIS.

eLife assessment

This useful paper reports on two simple methods for improving the efficiency of prime editing, a prominent gene editing technique. In combination with published modifications, the strategies described in this study may lead to significant improvements in editing efficiencies. The data are solid, and the methods will be of broad interest to anyone using gene editing.

eLife assessment

This study highlights several important regulatory pathways that contribute to the control of entry into meiosis by turning down mitotic functions. Central to this regulation is the control of Swi4 level and activity, and convincing overexpression experiments identify downstream effectors of Swi4.

eLife assessment

This study reveals a novel mechanism of Acetylcholine- Acetylylcholine receptor signaling in regulating gut barrier function in Drosophila, which provides important implications on the pathway played in human diseases, such as Chronic Obstructive Pulmonary DiseaseCOPD. The evidence supporting the claims of the authors is solid.

eLife assessment

This important study identifies the gene mamo as a new regulator of pigmentation in the silkworm Bombyx mori, a function that was previously unsuspected based on extensive work on Drosophila where the mamo gene is involved in gamete production. The evidence supporting the role of Bm-nano in pigmentation is convincing, including high-resolution linkage mapping of two mutant strains, expression profiling, and reproduction of the mutant phenotypes with state-of-the-art RNAi and CRISPR knock-out assays. The work will be of interest to evolutionary biologists and geneticists studying color patterns and evolution of gene networks.

eLife assessment

The paper addresses the mechanism of initiation of DNA replication in human cells by analyzing published data on the location of origins of DNA replication and the location of binding sites in the genome for ORC and MCM2-7 complexes. There are some useful analyses of existing data but there are concerns regarding the conclusion that there might be alternative mechanisms for determining the location of origins of DNA replication in human cells compared to the well known mechanism known from many eukaryotic systems, including yeast, Xenopus, C. elegans and Drosophila. The lack of overlap between binding sites for ORC1 and ORC2, which are known to form a complex in human cells, is a particular concern and points to the evidence for the accurate localization of their binding sites in the genome being incomplete.

eLife assessment

This valuable study describes mice with a knock out of the IQ motif-containing H (IQCH) gene, to model a human loss-of-function mutation in IQCH associated with male sterility. The infertility is reproduced in the mouse, making it a compelling model, but some of the mechanistic experiments provide only indirect and thus incomplete evidence for interaction between IQCH and potential RNA binding proteins. With more rigorous approaches, the paper should be of interest to cell biologists and male reproductive biologists working on the sperm flagellar cytoskeleton and mitochondrial structure.

eLife assessment

This valuable study advances our understanding of the forces that shape the genomic landscape of transposable elements. By exploiting both long-read sequencing of mutation accumulation lines and in vivo transposition assays, the authors offer compelling evidence that structural variation rather than transposition largely shapes transposable element copy number evolution in budding yeast. The work will be of interest to the transposable element and genome evolution communities.

eLife assessment

Moises and Harel generate an important set of novel molecular tools in African turquoise killifish, an innovative model to study aging biology. The new solid tools described in this paper can boost this buddying model system for broad biotechnological applications. The authors showcase the efficacy of their tools in the context of peptide hormones involved in growth and gonad development. The killifish community will greatly benefit from these novel tools and the relevance of the developed methods will likely go beyond the killifish community.

eLife assessment

This solid study addresses the unresolved question of why many thousands of small-effect loci contribute more to the heritability of a trait than the large-effect lead variants. The authors explore resource competition within the transcriptional machinery as one possible explanation with a simple theoretical model, concluding that the effects of resource competition would be too small to explain the heritability effects. The topic and approximation of the problem are important and offer an intuitive way to think about polygenic variation, but there are concerns on the derivation of the equations with respect to dropping vs. including certain terms that deal inherently with small numbers.

eLife assessment

This useful study presents a genetically encoded barcoding system that could not only advance transcriptomic studies but that also has potential further applications, such as in high-throughput population-scale behavioral measurements. The evidence supporting the claims of the authors are currently inadequate to demonstrate that the method is indeed greatly superior to existing approaches in behavioural and transcriptomic studies.

eLife assessment

This valuable study uses population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Computational prediction of human-specific lncRNAs and their DNA binding sites and analyses of these loci lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. The evidence supporting the conclusions is, however, still incomplete, as key details regarding the methodology and analyses are lacking.

eLife assessment

How the genome is folded three dimensionally is thought to control gene regulatory pathways during critical processes such as cellular differentiation. Using multiple assays, the authors of this important study probe topologically associated domains (TADs) and report involvement of a protein arginine methyltransferase 5 in chromatin organization and transcriptional regulation. The data gathered are generally solid and broadly support the role of this protein in organization of the adipocytic lineage, but additional control experiments would make the inferences stronger.

eLife assessment

The study presents valuable findings on how the hypoxia response pathway senses and responds to changes in the homeostasis of the amino acid cysteine and other sulfur-containing molecules. By providing a compelling, rigorous genetic analysis of the pathway, the study adds to a growing body of literature showing that prolyl hydroxylation is not the only mechanism by which the hypoxia response pathway can act. Although the paper does not reveal new biochemical insight into the mechanism, it opens up new areas of investigation that will be of interest to cell biologists and biomedical researchers studying the many pathologies involving hypoxia and/or cysteine metabolism.