Biology subjects

Nagendra, P.

Publications and source records attributed to Nagendra, P..

4 recordsLinked to original sources

bioRxiv2026

Asexual Adaptation Drives Transient and Reversible Changes in Mating Efficiency.

The evolution of reproductive isolation is central to speciation, yet the earliest stages of this process remain poorly understood. In particular, it is unclear how rapidly barriers to mating arise during adaptation, whether they accumulate predictably, and how they depend on ecological context. Here, we investigate the evolution of mating efficiency during prolonged asexual adaptation in diploid Saccharomyces cerevisiae. Twelve replicate populations were evolved for 1200 generations in two distinct carbon environments, glucose and galactose, under strictly asexual conditions. At regular intervals, we induced sporulation and quantified mating efficiency using three complementary assays: within-population crosses, crosses between populations evolved in different environments, and crosses between evolved populations and the ancestral strain. We find that mating efficiency evolves during asexual adaptation, with outcomes that depend strongly on the environment. While glucose-evolved populations remain largely stable, galactose-evolved populations exhibit a reversible decline. Overall, changes in mating efficiency are dynamic, heterogeneous, and often transient, with evidence for both intrinsic reductions in mating competence and context-dependent incompatibilities between populations. Together, these results show that asexual adaptation can generate rapid but non-monotonic changes in mating compatibility. Early reductions in mating efficiency are heterogeneous, environment-dependent, and often reversible, and do not accumulate into stable reproductive isolation over the timescale examined. Our findings suggest that the initial stages of divergence are characterized by dynamic and contingent perturbations of reproductive traits, rather than a steady progression toward speciation.

evolutionary biology↗

bioRxiv2026

Reconstructing clone-resolved transcriptional programs from bulk tumor sequencing

Tumor clones acquire distinct transcriptional programs as they evolve, but bulk RNA-seq averages over clonal mixtures and obscures the lineage-specific biology that DNA-sequencing reveals. We present PICTographPlus, the first method to infer clone-resolved transcriptional programs by integrating bulk DNA-derived clonal phylogenies and proportions with bulk RNA-seq alone, without single-cell data. Benchmarked against experimentally measured ground truth, scDNA/scRNA co-profiled cells from a wellDR-seq cancer dataset, across 320 pseudo-bulk replicates spanning four tumor purities and four sample counts and evaluated under seven regularization models, PICTographPlus recovers clone-level expression at mean Pearson r [≥] 0.92 and localizes pathway gains and losses to correct evolutionary branches (median F1 0.31-0.40, well above a no-deconvolution baseline). Applied to multi-region NSCLC, pancreatic precursor lesions, and rapid-autopsy PDAC, it localizes metabolic reprogramming, precursor-to-invasive transitions, and organ-adapted metastatic states to specific clonal branches. PICTographPlus turns standard bulk assays into clone-resolved transcriptional maps, enabling retrospective analyses where single-cell profiling is impractical.

genomics↗

bioRxiv2025

Opposing Copy Number Variation Dynamics Shape Adaptation to Glucose and Galactose in Diploid Yeast

Adaptation to new environments arises from multiple forms of genetic variation, including single-nucleotide polymorphisms (SNPs) and structural variants such as copy number variations (CNVs). Although both mutation classes have been implicated in evolutionary change, their relative contributions during adaptation remain incompletely understood and may depend strongly on environmental context. Here we investigated genome evolution during experimental adaptation of diploid Saccharomyces cerevisiae populations propagated for 1200 generations in two alternative carbon sources, glucose or galactose. Whole-genome sequencing of replicate populations at multiple evolutionary time points revealed relatively few SNPs but widespread copy number variation across the genome. Strikingly, CNV dynamics differed markedly between environments. Populations evolved in glucose exhibited extensive early deletions followed by later genomic remodeling that reduced the overall deletion burden. In contrast, populations evolved in galactose accumulated persistent subtelomeric duplications throughout the experiment. Many loci displayed opposing copy number changes in the two environments, with genes deleted during evolution in glucose frequently duplicated during evolution in galactose. These contrasting trajectories indicate that structural genomic changes repeatedly arise during adaptation and that their direction and persistence depend strongly on environmental conditions. Together, our results illustrate how distinct genomic routes can emerge during adaptation of genetically identical populations and highlight the importance of considering multiple classes of mutations when studying evolutionary responses to environmental change. Impact statementThis study demonstrates that copy number variations (CNVs), rather than single-nucleotide polymorphisms, dominate genome evolution during adaptation of diploid Saccharomyces cerevisiae to alternative carbon sources. By evolving genetically identical populations in glucose and galactose, the work reveals that environmental context drives strikingly opposing CNV trajectories, widespread deletions in glucose and persistent duplications in galactose, often targeting the same genomic loci in opposite directions. These findings provide direct evidence that structurally mediated gene dosage changes are a primary and environment-dependent mechanism of adaptation, reshaping metabolic networks and specialization strategies. More broadly, the study challenges the prevailing SNP-centric view of adaptive evolution and highlights CNVs as a predictable and major axis of genome remodeling in microbial systems.

evolutionary biology↗

bioRxiv2023

Rapid evolution of pre-zygotic reproductive barriers in allopatric populations.

Adaptive divergence leading to speciation is the major evolutionary process generating diversity in life forms. The most commonly observed form of speciation is allopatric speciation which requires that gene flow be prevented between populations by physical or temporal barriers, as they adapt to their respective environments. Eventually, these adaptive responses drive the populations far apart in the genotypic space such that individuals from the two populations become reproductively isolated. A widely accepted theory is that speciation simply occurs as a by-product of adaptive response of the populations1,2. Several ecological and laboratory examples of allopatric speciation exist3-6. However, we know little about the nature (pre- or post-zygotic) of barriers that arise first in this process. Understanding the first barriers that arise between populations is key, as populations diverge towards becoming distinct species. In recent years, fungi been used as model organisms to answer questions related to evolution of reproductive isolation3,7-9. Here we show rapid evolution of pre-zygotic barriers between allopatric yeast populations. We further demonstrate that these pre-zygotic barriers arise due to altered mating kinetics of the evolved population. Moreover, our non-adaptive evolution experiments with yeast under limited selection pressure also show rapid emergence of reproductive isolation. Overall, our results show that evolution of pre-zygotic reproductive barriers can occur as result of natural selection or drift. These barriers result because of altered mating kinetics or mate preference. One sentence summaryPre-zygotic barriers to gene flow can arise due to adaptation or drift.

evolutionary biology↗