{ "abstract": "Heart rate (HR) is a complex quantitative phenotype that is influenced by both genetic and environmental factors, and it is a critical factor in the regulation of cardiac physiology. Despite the discovery of numerous genes associated with HR variation in humans and other organisms, the mechanisms by which these genes interact to affect HR changes in natural environments and their responses to environmental stressors remain incompletely understood. In this study, the genetic basis of basal HR and the response to salt stress were examined using the Drosophila Genetic Reference Panel (DGRP). The 154 DGRP lines exhibited moderate broad-sense heritability and substantial genetic variation in HR measurements during the third larval stage, with males and females analyzed separately, under both standard and 0.1% NaCl-containing medium conditions. The mixed-effects model revealed that the interaction between genotype and environment significantly influences HR. Genome-wide association analysis identified gene variants associated with critical biological processes such as ion transport, cardiac development, protein homeostasis, metabolism, and stress response. The identification of different genes under standard and saline (NaCl-supplemented) conditions suggests that environmental stress unlocks cryptic genetic variation. Candidate genes were tested using heart-specific GAL4 drivers in RNAi experiments, and a considerable number of these genes were found to significantly affect HR based on sex and the environment. These findings reveal that HR variation is strongly shaped by genotype-by-environment interactions and sex-specific genetic effects, with distinct sets of genes contributing under basal and stress conditions. The identification of environment-dependent genetic architectures suggests that salt stress can expose cryptic genetic variation influencing cardiac function. By integrating genome-wide association analyses with targeted RNAi-based functional validation, this study provides a framework for linking natural genetic variation to physiological phenotypes in a context-dependent manner. Author summary: HR is a vital physiological characteristic for life and an important marker for detecting heart disease. This marker is a trait influenced by both genetic factors and environmental factors, but the underlying genetic mechanisms and how they interact with environmental conditions are not well understood. In this study, we investigated the genetic architecture of HR using natural genetic variation in the fruit fly Drosophila melanogaster. By analyzing genotype × environment interactions under dietary salt treatment, we demonstrated how environmental stress reveals hidden genetic variation. Functional experiments demonstrate that HR is regulated by genetic networks associated with ion homeostasis and cellular regulatory mechanisms. Our findings indicate that the genetic architecture of this complex trait is responsive to the environmental context and modulated by evolutionarily conserved mechanisms.", "abstract_shown": true, "affiliations": [ "Faculty of Science, Department of Biology, Functional and Evolutionary Genetics Laboratory, Hacettepe University, Ankara, Türkiye", "Hacettepe University the Institute for Graduate Studies of Science and Engineering, Ankara, Türkiye", "Institute for Human Genetics and Department of Genetics and Biochemistry, Clemson University, Greenwood, South Carolina, United States of America", "Atatürk University, Department of Medical Biology, Faculty of Medicine, Erzurum, Türkiye" ], "article_type": "Research Article", "arxiv": null, "author_total": 5, "authors": [ { "affs": [ 0 ], "name": "Gulnur Ipek Erdemli" }, { "affs": [ 1 ], "name": "Murat Yilmaz" }, { "affs": [ 2 ], "name": "Alp Mete Ummet" }, { "affs": [ 3 ], "name": "Fatih Akdemir" }, { "name": "Ergi Deniz Ozsoy" } ], "bibtex": "https://research.draconitic.com/paper/41cendta7ec8y.bib", "cited_by": 0, "doi": "10.1371/journal.pgen.1012313", "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012313", "id": "41cendta7ec8y", "issns": [ "1553-7404" ], "landing_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012313", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2804|Neurobiology and Insect Physiology Research" ], [ "plos", "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/RNA interference" ], [ "plos", "/Biology and life sciences/Computational biology/Genome analysis/Genome-wide association studies" ], [ "plos", "/Biology and life sciences/Developmental biology/Life cycles/Larvae" ], [ "plos", "/Biology and life sciences/Evolutionary biology/Population genetics/Genetic polymorphism" ], [ "plos", "/Biology and life sciences/Genetics" ], [ "plos", "/Biology and life sciences/Genetics/Epigenetics/RNA interference" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/RNA interference" ], [ "plos", "/Biology and life sciences/Genetics/Genetic interference/RNA interference" ], [ "plos", "/Biology and life sciences/Genetics/Genomics/Genome analysis/Genome-wide association studies" ], [ "plos", "/Biology and life sciences/Genetics/Human genetics/Genome-wide association studies" ], [ "plos", "/Biology and life sciences/Genetics/Phenotypes" ], [ "plos", "/Biology and life sciences/Genetics/Population genetics/Genetic polymorphism" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Biology and life sciences/Population biology/Population genetics/Genetic polymorphism" ], [ "plos", "/Biology and life sciences/Zoology/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Biology and life sciences/Zoology/Entomology/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Drosophila melanogaster" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Drosophila melanogaster" ], [ "plos", "/Research and analysis methods/Model organisms/Drosophila melanogaster" ] ], "openalex": "W7220430716", "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012313&type=printable", "pmcid": null, "pmid": null, "published": "2026-10-05", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/41cendta7ec8y.ris", "sources": [ { "first_seen": "2026-10-30T12:17:37Z", "native_id": "10.1371/journal.pgen.1012313", "source": "plos", "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012313" } ], "subjects": [ { "field": "biology", "origin": "plos:genetics", "subfield": "genetics-genomics" } ], "title": "Genetic architecture of basal heart rate and its modulation by dietary salt in Drosophila melanogaster", "title_text": "Genetic architecture of basal heart rate and its modulation by dietary salt in Drosophila melanogaster", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:37Z", "url": "https://research.draconitic.com/paper/41cendta7ec8y", "venue": "PLOS Genetics", "versions": [] }