Volume 15, Issue 8, August 2025

Aberrant accumulation of the metabolite D-2-hydroxyglutarate (D-2HG) is implicated in cancer progression and neurometabolic disorders, though its pathological effects vary depending on genetic context. To explore how genetic background influences D-2HG-associated phenotypes, Rai et al. generated two loss-of-function alleles in the Drosophila melanogaster gene D2hgdh, which encodes the enzyme responsible for degrading D-2HG. These mutants exhibit elevated D-2HG levels along with distinct developmental and metabolic abnormalities. Overall, the authors’ efforts provide the Drosophila community with new mutant strains that can be used to study D-2HG function in human disease models as well as in the context of normal growth, metabolism, and physiology.

This work addresses the biodiversity, phylogenetic relationships, and genetic incompatibilities of Caenorhabditis nematodes, which are laboratory model organisms. Through field studies, the authors isolated 60 Caenorhabditis strains in Indonesia, representing ten species, including five newly described. From RNA sequencing and phylogenetic reconstruction, all ten species belong to the Elegans group of Caenorhabditis. In crosses between closely related species, the hybrid progeny can be all females, abiding by Haldane’s rule, but in other cases all males. In one species pair, partially fertile hybrids are produced in one cross direction. These closely related species are good models for studying genetic incompatibilities.

Inferring the source population of genetic markers in an individual, or local ancestry inference (LAI), is important for numerous applications in genetics. However, few independent analyses of existing LAI methods’ performance have been done, and while the impact of phase uncertainty on LAI is broadly appreciated, this relationship has not been examined in detail. Avadhanam and Williams’ work aims to bridge this gap and their findings indicate that in datasets with thousands of individuals, phase-free approaches outperform phase-based approaches.

Reproduction in the parasitic wasp Trichogramma kaykai is determined by the presence of a bacterial symbiont that converts offspring to female (“parthenogenesis”), and a selfish male-making chromosome. This work presents sequencing, assembly, and analysis of the wasp’s genome, and that of its Wolbachia symbiont. Genes involved in parthenogenesis induction are identified and comparative analyses across Trichogramma reveal conservation within the genus. These genome resources will enhance our ability to study reproductive biology and support a foundational understanding of Trichogramma, which are applied globally to manage agricultural pests.

Validation of genomic predictions or polygenic risk scores is crucial for model selection and validating the performance of the chosen model. Non-parametric cross-validation does not consider population structure, and that not all individuals are of the same interest for validation. Semi-parametric validation overcomes these issues. Bermann et al. developed a software called validationf90, which performs semi-parametric validation within the Blupf90 software suite. This type of validation, as well as the software tool, is applicable to animal, plant, and human datasets.