Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.10.16.759659

Interaction of combined stressors and genetic background on recombination rate plasticity in Drosophila melanogaster

Abstract

Recombination is an important source of genetic variation and plays a central role in adaptation and genome stability. Although environmental conditions such as temperature can alter recombination rates, much less is known about how multiple environmental stressors act together. Here, we tested the effects of low temperature and hypoxia, both independently and in combination, on recombination in Drosophila melanogaster across five genetic backgrounds. Using a quadruple X-linked marker stock, we measured recombination in 50,209 male backcross progeny from 194 backcrosses exposed to four conditions: control, hypoxia, low temperature, and combined hypoxia and low temperature. Low temperature significantly altered recombination across all three chromosome intervals examined and affected total map length with an average increase of 5 cM. Genetic background strongly influenced the magnitude of altered recombination rate. Hypoxia alone did not significantly change total map length, but its effects differed among genetic backgrounds with significant variation in both the magnitude and direction with an average decrease of 0.96 cM. The response to combined hypoxia and low temperature was not simply the sum of the responses to each stressor alone, with an average increase of 6.78 cM, that also varied across genetic backgrounds in magnitude and direction as well as over time. DGRP_57 and DGRP_508 showed some of the largest increases in recombination under combined stress, whereas DGRP_491 showed a decrease. DGRP_391 was robust across all treatments. Despite these changes in crossover frequency, crossover interference remained largely stable across treatments, with only the y-cv-v interval pair showing a significant treatment-by-genotype interaction. Together, these results show that recombination responses to environmental stress depend strongly on genetic background and on the combination of stressors experienced. Our findings highlight the importance of considering both genetic variation and interacting environmental conditions when predicting how populations may respond to increasingly complex environmental change.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rivera-Rincon, N. R., Saurette, E. C., Havard, L. G., Stevison, L. S.. 2026-10-22. Interaction of combined stressors and genetic background on recombination rate plasticity in Drosophila melanogaster. https://doi.org/10.64898/2026.10.16.759659

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Alzheimer's disease-associated rs28834970 variant in PTK2B impairs electrical activity and regulates Tau phosphorylation and APP processing in human neuronal cultures

Background: Genome-wide association studies have identified the PTK2B gene, which encodes Proline-rich tyrosine kinase 2 (PYK2), as a genetic risk factor for Alzheimer's disease (AD). However, its role in AD aetiology remains to be understood, as a complex contribution to amyloid {beta} (A{beta}) toxicity, tauopathy and neuronal dysfunction is suggested by contradictory evidence. Determining how the causal variant among AD-associated PTK2B variants impairs PYK2 function to trigger AD hallmarks could bring clarification. Methods: We combined in silico prediction tools with luciferase reporter assays in neuroblastoma cells to prioritize potential AD-associated PTK2B functional variants. We generated isogenic KOLF2.1J induced pluripotent stem cells (iPSCs) carrying the most relevant functional variant using CRISPR-Cas9 and differentiated them into human neuronal cultures (hNCs). We assessed PYK2 expression via immunoblotting, performed transcriptomic profiling using RNA-sequencing, analyzed neuronal network activity via multielectrode array (MEA) recordings, quantified synaptic density through immunocytochemistry in microfluidic devices, and assessed Tau phosphorylation and amyloid-precursor protein (APP) metabolism. Results: The rs28834970 regulatory variant was identified as the most functionally relevant in our model, with the C risk allele promoting transcription factor C/EBP{beta} binding within a cis-regulatory element. In hNCs, the homozygous rs28834970 CC genotype reduced total PYK2 levels by more than 80%, while increasing the proportion of phosphorylated (activated) PYK2. Transcriptomic analysis revealed 724 downregulated and 113 upregulated gene sets, with altered expression of genes involved in extracellular matrix organization, cytoplasmic translation and neurotransmitter secretion. MEA recordings showed reduced network recruitment and altered burst organization. Immunocytochemistry in microfluidic devices consistently revealed that rs28834970 impacts dendritic development and postsynaptic maturation. The risk genotype significantly elevated Tau phosphorylation at pathological sites (Thr181, Thr217, Thr231, Ser202-Thr205, Ser396-Ser404), and enhanced APP processing, resulting in decreased levels of APP and CTF but increased levels of sAPP, sAPP{beta} and A{beta}. Conclusion: The rs28834970 C risk allele mechanistically links AD susceptibility to downregulation of PTK2B/PYK2 expression and to the increase in Tau pathology and A{beta} levels while compromising synaptic structure and function.

genetics↗

Human infection with an ape Plasmodium vivax-like parasite

An unusually divergent Plasmodium vivax parasite was reported in a Swedish patient with recent travel. Using whole-genome sequencing, we show that the infection was caused by a strain of ape P. vivax-like, providing evidence of the zoonotic potential of these parasites that infect wild gorillas and chimpanzees in central Africa.

genetics↗

Preclinical Development and Safety of Laterally Spreading Dual AAV.SPR-MYO7A Vectors for the Treatment of Usher Syndrome Type 1B

Usher syndrome type 1B (USH1B), caused by mutations in MYO7A, is the most severe form of Usher syndrome and accounts for more than 50% of USH1 cases. Affected patients are born profoundly deaf with vestibular dysfunction and develop progressive retinitis pigmentosa, for which no approved treatment exists. The MYO7A coding sequence exceeds the packaging capacity of adeno-associated virus (AAV), the gold standard vector for retinal gene therapy. To overcome this, we developed dual AAV hybrid and overlap platforms to reconstitute full-length MYO7A expression in photoreceptors and retinal pigment epithelium. Modification of cDNA split points, and reduction of non-coding sequence yielded optimized vector pairs that produced higher full-length MYO7A levels with substantially reduced truncated protein. Packaging in the laterally spreading AAV.SPR capsid enabled supraphysiological MYO7A expression in cynomolgus macaques at macular and distal retinal sites without requiring foveal detachment, an important safety consideration for USH1B patients with remaining central vision. A six-month GLP toxicology study confirmed that ATSN-301, an AAV.SPR-based dual vector reconstituting MYO7A driven by the smCBA promoter, was well tolerated at all doses, with a No Observed Adverse Effect Level established at 1.2E11 vg/eye, supporting its clinical advancement for USH1B.

genetics↗