Biology subjects

Kwakye, A.

Publications and source records attributed to Kwakye, A..

4 recordsLinked to original sources

bioRxiv2026

Variable jackpot individuals provide most alleles for repeated, rapid adaptation to freshwater by anadromous Threespine Stickleback

Experimental introductions of anadromous stickleback into freshwater habitats lacking this species allow analysis of the process of adaptation to freshwater forward-in-time. We examined the population genomic dynamics during early stages of adaptation in three replicate lakes that were experimentally founded, each using [~]3000 anadromous ancestors. We replicated earlier results that rare individuals carrying large haploblocks of freshwater-adaptive alleles (jackpot carriers) provide most of the allelic variation for adaptation of anadromous Threespine Stickleback to freshwater within only a few generations in each lake. There were population bottlenecks two to three generations after founding in each lake, after which jackpot carriers dramatically increased in frequency and came to dominate the populations. Individuals lacking large adaptive haploblocks experienced low fitness in their new freshwater environments, consistent with our previous report based on a single lake population. Despite similarities of the demographic responses to selection, the alleles that were most common among jackpot carriers were different in each population, suggesting that each lake population likely adapted to conditions in freshwater environments through different genes. These results provide direct evidence for the genomic mechanisms underlying the rapid adaptation of anadromous sticklebacks to freshwater environments, a process that can occur within just a few generations.

evolutionary biology↗

bioRxiv2026

Genomic signatures of selection are enriched in differentially expressed genes in sticklebacks adapting to contrasting environments

Whole genome scans have identified numerous adaptive alleles in many species; however, linking these alleles to specific phenotypes remains a major challenge. A promising alternative to direct genotype-phenotype mapping, particularly given the complexities introduced by epistasis, pleiotropy, and environmental variability, is to assess whether differentially expressed genes are enriched in regions of genetic divergence between populations adapted to contrasting environments. Here, we study gene expression patterns in threespine stickleback populations adapting to contrasting environments (marine vs freshwater) and investigate how signatures of selection interact with patterns of gene expression. We performed transcriptomic experiments of the brain and gill tissues of wild-caught sticklebacks sampled from one marine and two freshwater environments using TagSeq. We found that differentially expressed genes in the freshwater environments are enriched for single nucleotide polymorphisms (SNPs) previously identified to be involved in rapid adaptation and FST outliers. A majority of these SNPs were located in cis-regulatory regions with predicted low to moderate effects on protein function and structure, although we found a high-impact SNP in the gene col8a1b. Genes such as pvalb4 and acsl4a, involved in calcium regulation in the gill and fatty acid metabolism in the brain, respectively, were enriched with SNPs showing signatures of selection. By linking signatures of selection to tissue-specific gene expression patterns, our study bridges the gap between genomic divergence and the molecular mechanisms underlying physiological adaptation to new environments. Significance StatementUnderstanding how genetic variation translates into adaptive traits remains a central challenge in evolutionary biology. While whole-genome scans routinely identify candidate adaptive alleles, connecting these variants to functional phenotypes is complicated by epistasis, pleiotropy, and environmental effects. Here, we integrate signatures of selection with tissue-specific gene expression in threespine stickleback adapting to contrasting environments (marine and freshwater). We demonstrate that differentially expressed genes in freshwater populations are enriched for previously identified adaptive SNPs and FST outliers, many of which are located in cis-regulatory regions with predicted low to moderate functional effects. Notably, we identify a high-impact variant leading to a premature stop codon in col8a1b and highlight genes such as pvalb4 and acsl4a that link selection to key physiological processes, including ion regulation in gills and fatty acid metabolism in the brain. By connecting genomic divergence to regulatory and tissue-specific expression changes, this work provides a mechanistic framework for understanding how natural selection shapes complex physiological adaptation.

evolutionary biology↗

bioRxiv2025

Rare Jackpot Individuals Drive Rapid Adaptation in Threespine Stickleback

Recombination has long been considered the primary mechanism to bring beneficial alleles together, which can increase the speed of adaptation from standing genetic variation. Recombination is fundamental to the transporter hypothesis proposed to explain precise parallel adaptation in Threespine Stickleback. We studied an instance of freshwater adaptation in the Threespine Stickleback system using whole genomic data from an evolutionary time series to observe the genomic dynamics underlying rapid parallel adaptation. Our experiment showed that rapid adaptation to a freshwater environment depended on a few individuals with large haploblocks of freshwater-adaptive alleles (jackpot carriers) present among the anadromous (i.e., sea-run) founders at low frequencies. Biological kinship analyses indicate that mating among jackpot carriers and between jackpot carriers and non-jackpot individuals led to a rapid increase in freshwater-adaptive alleles within the first few generations. This process allowed the population to overcome a substantial bottleneck likely caused by the low fitness of first-generation stickleback with a few freshwater-adaptive alleles born in the lake. Additionally, we found evidence that the genetic load that emerged from population growth after the bottleneck may have been reduced through an increase in homozygosity by inbreeding, ultimately purging deleterious alleles. Recombination likely played a limited role in this case of very rapid adaptation.

evolutionary biology↗

bioRxiv2021

Integrative genomic and epigenomic analyses identified IRAK1 as a novel target for chronic inflammation-driven prostate tumorigenesis

The impacts of many inflammatory genes in prostate tumorigenesis remain understudied despite the increasing evidence that associates chronic inflammation with prostate cancer (PCa) initiation, progression, and therapy resistance. The overarching goal of this study was to identify dysregulated inflammatory genes that correlate with PCa progression and decipher their molecular mechanisms as well as clinical significance in PCa using integrative genomics, transcriptomics, and epigenomics approach. Our Weighted Gene Co-expression Analysis (WGCNA) and multivariate analysis identified 10 inflammatory genes: IRAK1, PPIL5/LRR1, HMGB3, HMGB2, TRAIP, IL1F5/IL36RN, ILF2, TRIM59, NFKBIL2/TONSL, and TRAF7 that were significantly associated with PCa progression. We explored the potentials of IRAK1 and other inflammatory genes as diagnostic and/or prognostic biomarkers by performing both KM survival and AUROC curve analyses. Our results indicate the clinical significance of these inflammatory genes in predicting the development and progression of PCa. IRAK1 was found to be overexpressed and hypomethylated in most PCa samples. A significantly high percentage of castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC) samples display copy number variations, especially amplification of the IRAK1 gene compared to the indolent prostate adenocarcinoma (PRAD) samples. Furthermore, we identified missense and frameshift mutations of IRAK1 in a few PRAD samples with potential functional implications. In conclusion, the results from this study suggest that IRAK1 dysregulation may be an important contributor to chronic prostatitis (inflammation) and PCa progression.

cancer biology↗