Biology subjects

Abdul-Rahman, F.

Publications and source records attributed to Abdul-Rahman, F..

4 recordsLinked to original sources

bioRxiv2025

Copy number variation facilitates rapid toggling between ecological strategies

A central question in evolutionary biology is how different types of mutations shape ecological strategy. Whereas both single nucleotide variants (SNVs) and copy number variants (CNVs) can alter gene dosage, it remains unclear whether CNVs confer unique adaptive advantages. Here, we show that CNVs do not mediate adaptive tracking in fluctuating environments, but instead act as reversible toggles between ecological strategies. Using a dual-fluorescent CNV reporter system in Saccharomyces cerevisiae, we tracked CNV dynamics at two transporter loci during long-term evolution under static and fluctuating nitrogen limitation. CNVs arose with high repeatability in static conditions but showed dampened or divergent dynamics in fluctuating environments, suggesting they do not track environmental change. Instead, we found that the ratio of copy number between the two loci, but not copy number at either locus alone, predicted ecological strategy: imbalanced CNV ratios defined specialists, while balanced ratios defined generalists. Evolution in static environments favored specialists whereas fluctuating environments favored generalists. Applying this framework to over 3,000 sequenced yeast genomes, we found generalist CNV signatures in both wild and domesticated strains, but specialist signatures exclusively in domesticated strains. These findings introduce a generalizable framework for predicting ecological strategy from genome structure, positioning CNV ratios as a molecular signature of niche breadth across evolutionary and ecological contexts.

evolutionary biology↗

bioRxiv2025

Segmental copy number amplifications are stable in the absence of selection

Copy number variants (CNVs) are DNA duplications and deletions that cause genetic variation, underlying rapid adaptive evolution. CNVs often confer selective advantages, but can also incur fitness costs. Evolution of Saccharomyces cerevisiae in nutrient-limited chemostats recurrently selects for amplifications of nutrient transporter genes. However, their fate upon return to a non-selective environment remains unknown. To investigate CNV fitness and stability upon removing the original selection pressure, we studied 15 CNV lineages (11 segmental, 4 whole-chromosomal amplifications) selected in nitrogen-limited chemostats. CNV stability was monitored using fluorescent reporters during propagation in nutrient-rich batch cultures for 110-220 generations. All aneuploid lineages showed rapid CNV loss and reversion to a single-copy genotype, whereas segmental amplifications were remarkably stable- one of 11 strains reverted. Pairwise fitness competitions in rich media revealed strong fitness defects associated solely with CNVs that reverted; reversion led to increased fitness. Using simulation-based inference to estimate reversion rates and fitness effects, we determined negative selection as the primary driver of CNV loss. Whole-genome sequencing revealed that reversion of aneuploids and a segmental amplification left no evidence of prior CNV existence, rendering revertant genomes indistinguishable from the single-copy ancestor. Detailed characterization of a partial revertant identified chromosomal translocation, suggesting that extant CNVs can undergo structural diversification. Our findings provide novel evidence that most segmental CNVs adapted to nitrogen limitation are stable upon removal of selection, but costly gene amplifications are readily reversible. Together, these highlight the importance of CNVs in both long-term genome evolution and rapid, reversible adaptation to transient selection.

evolutionary biology↗

bioRxiv2024

DNA replication errors are a major source of adaptive gene amplification

Copy number variants (CNVs)--gains and losses of genomic sequences--are an important source of genetic variation underlying rapid adaptation and genome evolution. However, despite their central role in evolution little is known about the factors that contribute to the structure, size, formation rate, and fitness effects of adaptive CNVs. Local genomic sequences are likely to be an important determinant of these properties. Whereas it is known that point mutation rates vary with genomic location and local DNA sequence features, the role of genome architecture in the formation, selection, and the resulting evolutionary dynamics of CNVs is poorly understood. Previously, we have found that the GAP1 gene in Saccharomyces cerevisiae undergoes frequent and repeated amplification and selection under long-term experimental evolution in glutamine-limiting conditions. The GAP1 gene has a unique genomic architecture consisting of two flanking long terminal repeats (LTRs) and a proximate origin of DNA replication (autonomously replicating sequence, ARS), which are likely to promote rapid GAP1 CNV formation. To test the role of these genomic elements on CNV-mediated adaptive evolution, we performed experimental evolution in glutamine-limited chemostats using engineered strains lacking either the adjacent LTRs, ARS, or all elements. Using a CNV reporter system and neural network simulation-based inference (nnSBI) we quantified the formation rate and fitness effect of CNVs for each strain. We find that although GAP1 CNVs repeatedly form and sweep to high frequency in strains with modified genome architecture, removal of local DNA elements significantly impacts the rate and fitness effect of CNVs and the rate of adaptation. We performed genome sequence analysis to define the molecular mechanisms of CNV formation for 177 CNV lineages. We find that across all four strain backgrounds, between 26% and 80% of all GAP1 CNVs are mediated by Origin Dependent Inverted Repeat Amplification (ODIRA) which results from template switching between the leading and lagging strand during DNA synthesis. In the absence of the local ARS, a distal ARS can mediate CNV formation via ODIRA. In the absence of local LTRs, homologous recombination mechanisms still mediate gene amplification following de novo insertion of retrotransposon elements at the locus. Our study demonstrates the remarkable plasticity of the genome and reveals that template switching during DNA replication is a frequent source of adaptive CNVs.

evolutionary biology↗

bioRxiv2021

Fluctuating environments maintain genetic diversity through neutral fitness effects and balancing selection

Genetic variation is the raw material upon which selection acts. The majority of environmental conditions change over time and therefore may result in variable selective effects. How temporally fluctuating environments impact the distribution of fitness effects and in turn population diversity is an unresolved question in evolutionary biology. Here, we employed continuous culturing using chemostats to establish environments that switch periodically between different nutrient limitations and compared the dynamics of selection to static conditions. We used the pooled Saccharomyces cerevisiae haploid gene deletion collection as a synthetic model for populations comprising thousands of unique genotypes. Using barcode sequencing (barseq), we find that static environments are uniquely characterized by a small number of high fitness genotypes that rapidly dominate the population leading to dramatic decreases in genetic diversity. By contrast, fluctuating environments are enriched in genotypes with neutral fitness effects and an absence of extreme fitness genotypes contributing to the maintenance of genetic diversity. We also identified a unique class of genotypes whose frequencies oscillate sinusoidally with a period matching the environmental fluctuation. Oscillatory behavior corresponds to large differences in short term fitness that are not observed across long timescales pointing to the importance of balancing selection in maintaining genetic diversity in fluctuating environments. Our results are consistent with a high degree of environmental specificity in the distribution of fitness effects and the combined effects of reduced and balancing selection in maintaining genetic diversity in the presence of variable selection.

evolutionary biology↗