Biology subjects

Esposito, U.

Publications and source records attributed to Esposito, U..

3 recordsLinked to original sources

bioRxiv2019

A genomic dating tool for ancient genomes resolves the origins of hundreds of Eurasian genomes

Radiocarbon dating is the gold-standard in archaeology to estimate the age of skeletons, a key to studying their origins. Nearly half of all published ancient human genomes lack reliable and direct dates, which results in obscure and contradictory reports. Here, we developed the Temporal Population Structure (TPS), the first DNA-based dating method for ancient genomes ranging from the Upper Palaeolithic to modern-day samples and applied it to 1559 ancient Europeans, Asians, and Caucasus individuals and to 2117 modern worldwide individuals. We show that TPS predictions for dated skeletons align with their known dates and correctly account for kin relationships. The TPS-dating of poorly dated Eurasian samples resolves conflicts and sheds new light on disputed findings, as illustrated by four test cases. We discuss the phenotypic traits of the Time Informative Markers (TIMs) that underlie TPS. SummaryTPS is a novel method to date humans from the Upper Palaeolithic to modern time from their DNA sequences. Accurate dating is essential to the interepretation of paleogemonic data.. The gold-standard method in archaeology is radiocarbon dating1. However, a major limitation of radiocarbon dating is the high amount of collagen extraction (500 mg) involved in the process2. Consequently, half of all published ancient human genomes lack reliable and direct dates, which results in obscure and contradictory reports. Here, we present the Temporal Population Structure (TPS), the first genomic dating method for ancient genomes ranging from the Upper Palaeolithic to modern-day samples. We show that TPS predictions for 961 radiocarbon-dated Eurasian skeletons align with their known dates. We replicate these findings on 598 other Europeans, Asians and Caucasus individuals. Using kin-pairs, we demonstrate that TPS has produced more accurate results than radiocarbon and other dating. We show how our findings resolve conflicts and sheds new light on disputed findings as illustrated by four test cases. Finally, we discuss the phenotypic traits of the Time Informative Markers (TIMs) that underlie TPS. TPS is a novel dating technique, which can be used when radiocarbon dating is unfeasible or uncertain or to develop alternative hypotheses. TPS cannot be used for older (<14,000 years ago) samples, and its accuracy depends on the temporal and geographical breadth of radiocarbon-dated samples in the training dataset, though this limitation can be improved over time. Overall, TPS can improve the accuracy of archeological and paleogenomic studies.

genomics↗

bioRxiv2019

Regulation of neuron-specific gene transcription by stress hormone signalling requires synaptic activity in zebrafish

The Glucocorticoid Receptor (GR) co-ordinates metabolic and behavioural responses to stressors. We hypothesised that GR influences behaviour by modulating specific epigenetic and transcriptional processes in the brain. Using the zebrafish as a model organism, the brain methylomes of wild-type and grs357 mutant adults were analysed and GR-sensitive, differentially methylated regions (GR-DMRs) were identified. Two genes with GR-DMRs exhibited distinct methylation and transcriptional sensitivities to GR: the widely expressed direct GR target fkbp5 and neuron-specific aplp1. In larvae, neural activity is required for GR-mediated transcription of aplp1, but not for that of fkbp5. GR regulates metabotropic glutamate receptor gene expression, the activities of which also modulated aplp1 expression, implicating synaptic neurotransmission as an effector of GR function upstream of aplp1. Our results identify two distinct routes of GR-regulated transcription in the brain, including a pathway through which GR couples endocrine signalling to synaptic activity-regulated transcription by modulating metabotropic glutamate receptor expression.

developmental biology↗

bioRxiv2018

Ancient ancestry informative markers for identifying fine-scale ancient population structure in Eurasians

The rapid accumulation of ancient human genomes from various areas and time periods potentially allows the expansion of studies of biodiversity, biogeography, forensics, population history, and epidemiology into past populations. However, most ancient DNA (aDNA) data were generated through microarrays designed for modern-day populations known to misrepresent the population structure. Past studies addressed these problems using ancestry informative markers (AIMs). However, it is unclear whether AIMs derived from contemporary human genomes can capture ancient population structure and whether AIM finding methods are applicable to ancient DNA (aDNA) provided that the high missingness rates in ancient, oftentimes haploid, DNA can also distort the population structure. Here, we define ancient AIMs (aAIMs) and develop a framework to evaluate established and novel AIM-finding methods in identifying the most informative markers. We show that aAIMs identified by a novel principal component analysis (PCA)-based method outperforms all competing methods in classifying ancient individuals into populations and identifying admixed individuals. In some cases, predictions made using the aAIMs were more accurate than those made with a complete marker set. We discuss the features of the ancient Eurasian population structure and strategies to identify aAIMs. This work informs the design of population microarrays and the interpretation of aDNA results.

genetics↗