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Karageorgiou, C.

Publications and source records attributed to Karageorgiou, C..

5 recordsLinked to original sources

Convergent evolution through independent rearrangements in the primate amylase locus

Structurally complex genomic regions can foster evolutionary convergence by repeatedly generating gene duplications that yield similar expression patterns and traits across lineages. Focusing on the primate amylase locus, we leveraged high-quality genome assemblies from 53 primate species and multi-tissue transcriptomes from Old World monkeys to reconstruct the evolutionary history of recurrent duplications. We show that lineage-specific long terminal repeat retrotransposon insertions may be associated with initial structural instability, while subsequent duplications are primarily driven by non-allelic homologous recombination. Independent duplications in rhesus macaques, olive baboons, and great apes produced distinct amylase copies with convergent expression in pancreas and salivary glands and signals of episodic diversifying selection, consistent with emerging functional divergence. Our analyses indicate that a ancestral gene with dual pancreas and salivary expression in Catarrhini duplicated in great apes, facilitating subfunctionalization and regulatory rewiring. These findings illuminate how modular structural and regulatory variation drives evolutionary innovation and molecular convergence.

evolutionary biology↗

Adaptive Increase of Amylase Gene Copy Number in Peruvians Driven by Potato-rich Diets

Summary/AbstractThe salivary amylase gene (AMY1) exhibits remarkable copy number variation linked to dietary shifts in human evolution. While global studies highlight its structural complexity and association with starch-rich diets, localized selection patterns remain under explored. Here, we analyzed AMY1 copy number in 3,723 individuals from 85 populations, revealing that Indigenous Peruvian Andean populations possess the highest AMY1 copy number globally. A genome-wide analysis showed significantly higher amylase copy numbers in Peruvian Andean genomes compared to closely related populations. Further, we identified positive selection (selection coefficient of 0.0124, log likelihood ratio of 11.1543) at the nucleotide level on a haplotype harboring at least five haploid AMY1 copies, with a Peruvian Andean-specific expansion coinciding with potato domestication ([~]6-10 kya). Using ultra-long-read sequencing, we demonstrated that previously described recombination-based mutational mechanisms drive the formation of high-copy AMY1 haplotypes observed in Andean population. Our study provides a framework for investigating structurally complex loci and their role in human dietary adaptation.

genetics↗

Transcriptomics effects of per- and polyfluorinated alkyl substances in differentiated neuronal cells

Per- and polyfluorinated alkyl substances (PFAS) are pervasive environmental contaminants that bioaccumulate in tissues and pose risks to human health. Increasing evidence links PFAS to neurodegenerative and behavioral disorders, yet the underlying mechanisms of their effects on neuronal function remain largely unexplored. In this study, we utilized SH-SY5Y neuroblastoma cells, differentiated into neuronal-like cells, to investigate the impact of six PFAS compounds-- perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfonate (8:2 FTS), and 8:2 fluorotelomer alcohol (8:2 FTOH)--on neuronal health. Following a 30 M exposure for 24 hours, PFAS accumulation ranged from 100-7500 ng/mg of protein. Transcriptomic analysis revealed 721 differentially expressed genes (DEGs) across treatments (padj < 0.05), with 11 DEGs shared among all PFAS exposures, indicating potential biomarkers for neuronal PFAS toxicity. PFOA-treated cells showed downregulation of genes involved in synaptic growth and neural function, while PFOS, PFDS, 8:2 FTS, and 8:2 FTOH exposures resulted in upregulation of genes related to hypoxia response and amino acid metabolism. Lipidomic profiling further demonstrated significant fatty acid upregulation with PFDA, PFDS, and 8:2 FTS, alongside triacylglycerol downregulation with 8:2 FTOH. These findings suggest that the neurotoxic effects of PFAS are structurally dependent, offering insights into the molecular processes that may drive PFAS-induced neuronal dysfunction. SynopsisPer- and poly fluorinated alkyl substances (PFAS) have been shown to bioaccumulate in human tissues and affect health. This study aims to provide insights into the specific biological processes through which PFAS exposure affects neuronal cells.

pharmacology and toxicology↗

Ancient AMY1 gene duplications primed the amylase locus for adaptive evolution upon the onset of agriculture

Starch digestion is a cornerstone of human nutrition. The amylase genes code for the starch-digesting amylase enzyme. Previous studies suggested that the salivary amylase (AMY1) gene copy number increased in response to agricultural diets. However, the lack of nucleotide resolution of the amylase locus hindered detailed evolutionary analyses. Here, we have resolved this locus at nucleotide resolution in 98 present-day humans and identified 30 distinct haplotypes, revealing that the coding sequences of all amylase gene copies are evolving under negative selection. The phylogenetic reconstruction suggested that haplotypes with three AMY1 gene copies, prevalent across all continents and constituting about 70% of observed haplotypes, originated before the out-of-Africa migrations of ancestral modern humans. Using thousands of unique 25 base pair sequences across the amylase locus, we showed that additional AMY1 gene copies existed in the genomes of four archaic hominin genomes, indicating that the initial duplication of this locus may have occurred as far back 800,000 years ago. We similarly analyzed 73 ancient human genomes dating from 300 - 45,000 years ago and found that the AMY1 copy number variation observed today existed long before the advent of agriculture ([~]10,000 years ago), predisposing this locus to adaptive increase in the frequency of higher amylase copy number with the spread of agriculture. Mechanistically, the common three-copy haplotypes seeded non-allelic homologous recombination events that appear to be occurring at one of the fastest rates seen for tandem repeats in the human genome. Our study provides a comprehensive population-level understanding of the genomic structure of the amylase locus, identifying the mechanisms and evolutionary history underlying its duplication and copy number variability in relation to the onset of agriculture.

evolutionary biology↗

Genomic Analysis of Two Phlebotomine Sand Fly Vectors of Leishmania from the New and Old World

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the devastating kinetoplastid parasites of the genus Leishmania, the causative agents of diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. As no approved efficacious vaccine exists, available drugs are expensive and/or toxic, and resistance is emerging, management of sand fly populations to break transmission is currently the most effective disease control strategy. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two of the most important sand fly species: Phlebotomus papatasi, a cutaneous leishmaniasis vector, (distributed in the Middle East and North Africa) and Lutzomyia longipalpis, a visceral leishmaniasis vector (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites. Author SummaryThe leishmaniases are a group of neglected tropical diseases caused by protist parasites from the Genus Leishmania. Different Leishmania species present a wide clinical profile, ranging from mild, often self-resolving cutaneous lesions that can lead to protective immunity, to severe metastatic mucosal disease, to visceral disease that is ultimately fatal. Leishmania parasites are transmitted by the bites of sand flies, and as no approved vaccine exists, available drugs are toxic and/or expensive and resistance is emerging, new dual control strategies to combat these diseases must be developed, combining interventions on human infections and integrated sand fly population management. Effective vector control requires a good understanding of the biology of sand flies. To this end, we sequenced and annotated the genomes of two sand fly species that are important leishmaniasis vectors from the Old and New Worlds. These genomes allow us to better understand, at the genetic level, processes important in the vector biology of these species, such as finding hosts, blood-feeding, immunity, and detoxification. These genomic resources highlight the driving forces of evolution of two major Leishmania vectors and provide foundations for future research on how to better prevent leishmaniasis by control of the sand fly vectors.

genomics↗