Precise coordination between nutrient transporters ensures fertility in the malaria mosquito < i > Anopheles gambiae < /i >
by Iryna Stryapunina, Maurice A. Itoe, Queenie Trinh, Charles Vidoudez, Esrah Du, Lydia Mendoza, Oleksandr Hulai, Jamie Kauffman, John Carew, W. Robert Shaw, Flaminia Catteruccia Females from many mosquito species feed on blood to acquire nutrients for egg development. The oogenetic cycle has been characterized in the arboviral vectorAedes aegypti, where after a bloodmeal, the lipid transporter lipophorin (Lp) shuttles lipids from the midgut and fat body to the ovaries, and a yolk precursor protein, vitellogenin (Vg), is deposited into the oocyte by receptor-mediated endocytosis. Our understanding of how the roles of thes...
Source: PLoS Genetics - January 29, 2024 Category: Genetics & Stem Cells Authors: Iryna Stryapunina Source Type: research

Integration of expression QTLs with fine mapping via SuSiE
by Xiangyu Zhang, Wei Jiang, Hongyu Zhao Genome-wide association studies (GWASs) have achieved remarkable success in associating thousands of genetic variants with complex traits. However, the presence of linkage disequilibrium (LD) makes it challenging to identify the causal variants. To address this critical gap from association to causation, many fine-mapping methods have been proposed to assign well-calibrated probabilities of causality to candidate variants, taking into account the underlying LD pattern. In this manuscript, we introduce a statistical framework that incorporates expression quantitative trait locus (eQ...
Source: PLoS Genetics - January 25, 2024 Category: Genetics & Stem Cells Authors: Xiangyu Zhang Source Type: research

< i > Mycobacterium tuberculosis < /i > response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator
by Yue Chen, Nathan J. MacGilvary, Shumin Tan Successful colonization of the host requiresMycobacterium tuberculosis (Mtb) to sense and respond coordinately to disparate environmental cues during infection and adapt its physiology. However, how Mtb response to environmental cues and the availability of key carbon sources may be integrated is poorly understood. Here, by exploiting a reporter-based genetic screen, we have unexpectedly found that overexpression of transcription factors involved in Mtb lipid metabolism altered the dampening effect of low environmental potassium concentrations ([K+]) on the pH response of Mtb....
Source: PLoS Genetics - January 24, 2024 Category: Genetics & Stem Cells Authors: Yue Chen Source Type: research

Genetic drift promotes and recombination hinders speciation on holey fitness landscapes
by Ata Kalirad, Christina L. Burch, Ricardo B. R. Azevedo Dobzhansky and Muller proposed a general mechanism through which microevolution, the substitution of alleles within populations, can cause the evolution of reproductive isolation between populations and, therefore, macroevolution. As allopatric populations diverge, many combinations of alleles differing between them have not been tested by natural selection and may thus be incompatible. Such genetic incompatibilities often cause low fitness in hybrids between species. Furthermore, the number of incompatibilities grows with the genetic distance between diverging pop...
Source: PLoS Genetics - January 22, 2024 Category: Genetics & Stem Cells Authors: Ata Kalirad Source Type: research

Genome-wide analyses reveal the contribution of somatic variants to the immune landscape of multiple cancer types
In this report, we describe our effort of genome-wide association analyses across 22 TCGA cancer types to explore the associations between genetic alterations in cancer cells and 76 immune traits. Results showed that the tumor microenvironment (TME) is shaped by different gene mutations in different cancer types. Out of the key genes that drive multiple immune traits, top hit KEAP1 in lung adenocarcinoma (LUAD) was selected for validation. It was found that KEAP1 mutations can explain more than 10% of the variance for multiple immune traits in LUAD. Using public scRNA-seq data, further analysis confirmed that KEAP1 mutatio...
Source: PLoS Genetics - January 19, 2024 Category: Genetics & Stem Cells Authors: Wenjian Bi Source Type: research

Failure to mate enhances investment in behaviors that may promote mating reward and impairs the ability to cope with stressors via a subpopulation of Neuropeptide F receptor neurons
by Julia Ryvkin, Liora Omesi, Yong-Kyu Kim, Mali Levi, Hadar Pozeilov, Lital Barak-Buchris, Bella Agranovich, Ifat Abramovich, Eyal Gottlieb, Avi Jacob, Dick R. N ässel, Ulrike Heberlein, Galit Shohat-Ophir Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associa...
Source: PLoS Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Julia Ryvkin Source Type: research

The era of the ARG: An introduction to ancestral recombination graphs and their significance in empirical evolutionary genomics
by Alexander L. Lewanski, Michael C. Grundler, Gideon S. Bradburd In the presence of recombination, the evolutionary relationships between a set of sampled genomes cannot be described by a single genealogical tree. Instead, the genomes are related by a complex, interwoven collection of genealogies formalized in a structure called anancestral recombination graph (ARG). An ARG extensively encodes the ancestry of the genome(s) and thus is replete with valuable information for addressing diverse questions in evolutionary biology. Despite its potential utility, technological and methodological limitations, along with a lack of...
Source: PLoS Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Alexander L. Lewanski Source Type: research

Species-wide survey of the expressivity and complexity spectrum of traits in yeast
by Andreas Tsouris, T éo Fournier, Anne Friedrich, Jing Hou, Maitreya J. Dunham, Joseph Schacherer Assessing the complexity and expressivity of traits at the species level is an essential first step to better dissect the genotype-phenotype relationship. As trait complexity behaves dynamically, the classic dichotomy between monogenic and complex traits is too simplistic. However, no systematic assessment of this complexity spectrum has been carried out on a population scale to date. In this context, we generated a large diallel hybrid panel composed of 190 unique hybrids coming from 20 natural isolates representative of t...
Source: PLoS Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Andreas Tsouris Source Type: research

Correction: The Role of the Mammalian DNA End-processing Enzyme Polynucleotide Kinase 3 ’-Phosphatase in Spinocerebellar Ataxia Type 3 Pathogenesis
by Arpita Chatterjee, Saikat Saha, Anirban Chakraborty, Anabela Silva-Fernandes, Santi M. Mandal, Andreia Neves-Carvalho, Yongping Liu, Raj K. Pandita, Muralidhar L. Hegde, Pavana M. Hegde, Istvan Boldogh, Tetsuo Ashizawa, Arnulf H. Koeppen, Tej K. Pandita, Patricia Maciel, Partha S. Sarkar, Tapas K. Hazra (Source: PLoS Genetics)
Source: PLoS Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Arpita Chatterjee Source Type: research

Correction: Structural variation underlies functional diversity at methyl salicylate loci in tomato
by Manoj Sapkota, Lara Pereira, Yanbing Wang, Lei Zhang, Yasin Topcu, Denise Tieman, Esther van der Knaap (Source: PLoS Genetics)
Source: PLoS Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Manoj Sapkota Source Type: research

A major endogenous glycoside hydrolase mediating quercetin uptake in < i > Bombyx mori < /i >
by Ryusei Waizumi, Chikara Hirayama, Shuichiro Tomita, Tetsuya Iizuka, Seigo Kuwazaki, Akiya Jouraku, Takuya Tsubota, Kakeru Yokoi, Kimiko Yamamoto, Hideki Sezutsu Quercetin is a common plant flavonoid which is involved in herbivore –plant interactions. Mulberry silkworms (domestic silkworm,Bombyx mori, and wild silkworm,Bombyx mandarina) take up quercetin from mulberry leaves and accumulate the metabolites in the cocoon, thereby improving its protective properties. Here we identified a glycoside hydrolase, named glycoside hydrolase family 1 group G 5 (GH1G5), which is expressed in the midgut and is involved in querceti...
Source: PLoS Genetics - January 17, 2024 Category: Genetics & Stem Cells Authors: Ryusei Waizumi Source Type: research

A conserved transcription factor controls gluconeogenesis via distinct targets in hypersaline-adapted archaea with diverse metabolic capabilities
by Rylee K. Hackley, Angie Vreugdenhil-Hayslette, Cynthia L. Darnell, Amy K. Schmid Timely regulation of carbon metabolic pathways is essential for cellular processes and to prevent futile cycling of intracellular metabolites. InHalobacterium salinarum, a hypersaline adapted archaeon, a sugar-sensing TrmB family protein controls gluconeogenesis and other biosynthetic pathways. Notably,Hbt. salinarum does not utilize carbohydrates for energy, uncommon among Haloarchaea. We characterized a TrmB-family transcriptional regulator in a saccharolytic generalist,Haloarcula hispanica, to investigate whether the targets and functio...
Source: PLoS Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Rylee K. Hackley Source Type: research

The genome of < i > Litomosoides sigmodontis < /i > illuminates the origins of Y chromosomes in filarial nematodes
by Lewis Stevens, Manuela Kieninger, Brian Chan, Jonathan M. D. Wood, Pablo Gonzalez de la Rosa, Judith Allen, Mark Blaxter Heteromorphic sex chromosomes are usually thought to have originated from a pair of autosomes that acquired a sex-determining locus and subsequently stopped recombining, leading to degeneration of the sex-limited chromosome. The majority of nematodes species lack heteromorphic sex chromosomes and determine sex using an X-chromosome counting mechanism, with males being hemizygous for one or more X chromosomes (XX/X0). Some filarial nematode species, including important parasites of humans, have hetero...
Source: PLoS Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Lewis Stevens Source Type: research

Phosphoregulation of the yeast Pma1 H < sup > + < /sup > -ATPase autoinhibitory domain involves the Ptk1/2 kinases and the Glc7 PP1 phosphatase and is under TORC1 control
In this study, we show that S911-T912 phosphorylation in Pma1 is mediated by the largely redundant Ptk1 and Ptk2 kinase paralogs. Dephosphorylation of S911-T912, as occurs under glucose starvation, is dependent on the Glc7 PP1 phosphatase. Furthermore, proper S911-T912 phosphorylation in Pma1 is required for optimal TORC1 activation upon H+ influx coupled amino-acid uptake. We finally show that TORC1 controls S911-T912 phosphorylation in a manner suggesting that activated TORC1 promotes feedback inhibition of Pma1. Our results shed important new light on phosphoregulation of the yeast Pma1 H+-ATPase and on its interconnect...
Source: PLoS Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Nadia Guarini Source Type: research

Searching across-cohort relatives in 54,092 GWAS samples via encrypted genotype regression
In this study, we developedencG-reg, a regression approach that can detect relatives of various degrees based on encrypted genomic data, which is immune of ethical constraints. The encryption properties ofencG-reg are based on the random matrix theory by masking the original genotypic matrix without sacrificing precision of individual-level genotype data. We established a connection between the dimension of a random matrix, which masked genotype matrices, and the required precision of a study for encrypted genotype data.encG-reg has false positive and false negative rates equivalent to sharing original individual level dat...
Source: PLoS Genetics - January 11, 2024 Category: Genetics & Stem Cells Authors: Qi-Xin Zhang Source Type: research