Biology subjects

Eriksson, A.

Publications and source records attributed to Eriksson, A..

16 recordsLinked to original sources

bioRxiv2026

Massively parallel characterization reveals context-dependent and non-additive regulatory effects of closely spaced variant pairs

Precise control of gene expression relies in part on cis-regulatory elements (CREs), including enhancers. Genetic variation within enhancers can alter their regulatory activity and contribute to variation in gene expression, yet the effects of multiple nearby variants within the same enhancer remain poorly understood. To address this, we designed a massively parallel reporter assay (MPRA) to test the regulatory effect of 7,285 pairs of close-proximity single-nucleotide variants (SNVs) selected from blood-specific and broadly active enhancers. To enrich for functionality, we required at least one variant in each pair to be annotated as an eQTL in eQTLGen dataset. We measured the regulatory activity of all four haplotypes in K562 leukemia cells, where 57% of tested variant pairs had at least one derived haplotype that differed significantly in activity from the ancestral haplotype. The effects of individual variants frequently depended on the allelic background provided by the neighboring variant, with some variants showing opposite effects in different allelic backgrounds. Among a smaller, high-confidence subset selected for analysis of additivity, 59% (105/178) of variant pairs showed non-additive effects, and non-additive pairs were located closer together than additive pairs. Among pairs in which both single-derived haplotypes increased activity, the double-derived haplotype generally showed a smaller effect than expected under additivity. Together, our results demonstrate that nearby variants within the same enhancer can jointly shape regulatory activity and highlight the importance of considering local allelic context when interpreting the functional effects of regulatory variation.

genomics↗

bioRxiv2024

Resolving out of Africa event for Papua New Guinean population using neural network

The demographic history of the Papua New Guinean population is a subject of significant interest due to its early settlement in New Guinea, at least 50 thousand years ago, and its relative isolation compared to other out of Africa populations. This isolation, combined with substantial Denisovan ancestry, contributes to the unique genetic makeup of the Papua New Guinean population. Previous research suggested the possibility of admixture with an early diverged modern human population, but the extent of this contribution remains debated. This study re-examines the demographic history of the Papua New Guinean population using newly published samples and advanced analytical methods. Our findings demonstrate that the observed shifts in relative cross coalescent rate curves are unlikely to result from technical artefacts or contributions from an earlier out of Africa population. Instead, they are likely due to a significant bottleneck and slower population growth rate within the Papua New Guinean population. Our analysis positions the Papua New Guinean population as a sister group to other Asian populations, challenging the notion of Papua New Guinean as an outgroup to both European and Asian populations. This study provides new insights into the complex demographic history of the Papua New Guinean population and underscores the importance of considering population-specific demographic events in interpreting relative cross coalescent rate curves.

evolutionary biology↗

bioRxiv2023

The genetic legacy of the expansion of Bantu-speaking peoples in Africa

With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started [~]4000 years ago in western Africa. We have genotyped 1,740 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals. Our results show that Bantu speakers received significant gene-flow from local groups in regions they expanded into. We show for the first time that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the DRC as possible crossroads of interaction. Using spatially explicit methods and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial founder migration model. Finally, we discuss the utility of our dataset as an exhaustive modern-day African comparative dataset for ancient DNA studies. These new findings and data will be important to a wide range of disciplines from science and humanities as well as to the medical sector studying human genetic variation and health in African and African-descendant populations. One-sentence summaryA comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.

evolutionary biology↗

bioRxiv2022

A natural history of networks: Higher-order network modeling for paleobiology research

Paleobiologists are increasingly employing network-based methods to analyze the complex data retrieved from geohistorical records, including stratigraphic sections, sediments, and fossil collections. However, the lack of a common framework for designing, performing, evaluating, and communicating these studies, leads to issues of reproducibility and communicability. The high-dimensional geohistorical data also raises questions about the limitations of standard network approaches, which assume independent interactions between pairs of components. Higher-order network models better suited for the complex relational structure of the geohistorical data provide an opportunity to overcome these challenges. These models can represent temporal and spatial constraints inherent to the biosedimentary record and describe higher-order interactions, capturing more accurate biogeographical, biostratigraphic, and macroevolutionary patterns. Here we describe how to use the Map Equation framework for designing higher-order network models of geohistorical data, address some practical decisions involved in modeling complex dependencies, and discuss critical methodological and conceptual issues that currently make it difficult to compare results across studies in the growing body of network-based paleobiology research. We illustrate different higher-order network representations and models, including multilayers, hypergraphs, and varying Markov times models, using case studies on gradient analysis, bioregionalization, and macroevolution, and delineate future research directions for current challenges in the emerging field of network paleobiology.

paleontology↗

bioRxiv2021

Ancestral contributions to contemporary European complex traits

The contemporary European genetic makeup formed in the last 8000 years as the combination of three main genetic components: the local Western Hunter-Gatherers, the incoming Neolithic Farmers from Anatolia and the Bronze Age component from the Pontic Steppes. When meeting into the post-Neolithic European environment, the genetic variants accumulated during their three distinct evolutionary histories mixed and came into contact with new environmental challenges. Here we investigate how this genetic legacy reflects on the complex trait landscape of contemporary European populations, using the Estonian Biobank as a case study. For the first time we directly connect the phenotypic information available from biobank samples with the genetic similarity to these ancestral groups, both at a genome-wide level and focusing on genomic regions associated with each of the 27 complex traits we investigated. We also found SNPs connected to pigmentation, cholesterol, sleep, diastolic blood pressure, and body mass index (BMI) to show signals of selection following the post Neolithic admixture events. We recapitulate existing knowledge about pigmentation traits, corroborate the connection between Steppe ancestry and height and highlight novel associations. Among others, we report the contribution of Hunter Gatherer ancestry towards high BMI and low blood cholesterol levels. Our results show that the ancient components that form the contemporary European genome were differentiated enough to contribute ancestry-specific signatures to the phenotypic variability displayed by contemporary individuals in at least 11 out of 27 of the complex traits investigated here.

genomics↗

bioRxiv2021

Climate and mountains shaped human ancestral genetic lineages

Extensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.

genomics↗

bioRxiv2021

Dopamine facilitates fear memory formation in the human amygdala

Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced memory trace activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

neuroscience↗

bioRxiv2020

Windows out of Africa: A 300,000-year chronology of climatically plausible human contact with Eurasia

Whilst an African origin for Anatomically Modern Humans is well established 1, the timings of their expansions into Eurasia are the subject to heated debate, due to the scarcity of fossils and the lack of suitably old ancient DNA 2. Here, we estimate potential timings and routes out of Africa by deriving anthropologically and ecologically plausible precipitation requirements for human existence, and applying them to high-resolution palaeoclimate reconstructions for the past 300k years. We find that exit routes and timings previously suggested based on archaeological and genetic evidence coincide precisely with the presence of sufficiently wet corridors into Eurasia, while the gaps between the proposed exit timings co-occur with periods of insufficient rainfall. This demonstrates the key role that palaeoclimatic conditions played for out-of-Africa expansions. The challenging environmental conditions outside of Africa that occurred between windows of potential contact, coupled with the lack of a demographic rescue effect from migration and possible competition with other hominins, likely explain the demise of early colonists prior to the large-scale colonisation of the world beginning from [~]65kya.

evolutionary biology↗

bioRxiv2019

Regularities in species niches reveal the World's climatic regions

Although classifications of the Earths climates date back to the ancient Greeks, the climatic regions shaping the distribution of animals remain poorly resolved. Here we present a classification of global climates based on regularities in realised niches of 3657 amphibians, 7204 reptiles, 10684 birds and 4574 mammals. We found 16 main climatic regions that are mostly consistent across groups and previous plant expert-based classifications, confirming the existence of major climatic restrictions for life. The results also suggest that differences among groups likely relate to their particular adaptations and dispersal capabilities. We further show how the integration of species niche classifications with geographical information provides valuable information on potential mechanisms shaping the climatic regions. Our climate classification has applications in several disciplines, including conservation planning and ecological and evolutionary studies.

ecology↗

bioRxiv2019

Epidemiology of human culture: parietal rock art requires high population density

Demographic models of human cultural evolution have high explanatory potential but weak empirical support. Here we use a global dataset of rock art sites and climate and genetics-based estimates of ancient population densities to test a new model based on epidemiological principles. The model focuses on the process whereby a cultural innovation becomes endemic in a population. It predicts that this cannot occur unless population density exceeds a critical value. Analysis of the data, using a Bayesian statistical framework, shows that the model has stronger empirical support than a null model, where rock art detection rates and population density are independent, or a proportional model where detection is directly proportional to population density. Comparisons between results for different geographical areas and periods yield qualitatively similar results, supporting the robustness of the model. Re-analysis of the rock art data, using a second set of independent population estimates, yields similar results. We conclude that population density above a critical threshold is a necessary condition for the maintenance of rock art as a stable part of a populations cultural repertoire. Methods similar to those described can be used to test the model for other classes of archaeological artifact and to compare it against other models.

paleontology↗

bioRxiv2019

Secondary ossification centers evolved to make endochondral bone growth possible under the weight-bearing demands of a terrestrial environment

Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modelling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.

evolutionary biology↗

bioRxiv2018

Differential dominance of an allele of the Drosophila tbetah gene defies standard genetic techniques

The biogenic amine octopamine (OA) and its precursor tyramine (TA) are involved in controlling a plethora of different physiological and behavioral processes. The tyramine-{beta}-hydroxylase (t{beta}h) gene encodes the enzyme catalyzing the last synthesis step from TA to OA. Here, we report differential dominance (from recessive to overdominant) of the putative null t{beta}hnM18 allele in two behavioral measures in Buridans paradigm (walking speed and stripe deviation) and a proboscis extension assay in the fruit fly Drosophila melanogaster. The behavioral analysis of transgenic t{beta}h expression experiments in mutant and wild type flies as well as of OA- and TA-receptor mutants revealed a complex interaction of both aminergic systems. Our analysis suggests that the different neuronal networks responsible for the three phenotypes show differential sensitivity to t{beta}h gene expression levels. The evidence suggests that this sensitivity is brought about by a TA/OA opponent system modulating the involved neuronal circuits. This conclusion entails important implications for standard transgenic techniques, commonly used in functional genetics.

genetics↗

bioRxiv2018

Using Drosophila behavioral assays to characterize terebrid venom-peptide bioactivity

The number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and Tsu1.1 from Terebra subulata. Our results indicate that Tv1 and Tsu1.1 have distinct bioactivity. Tv1 (100 M) had an antinociceptive effect in adult Drosophila using a thermal nociception assay to measure heat avoidance. Alternatively, Tsu1.1 (100 M) increased food intake. These findings describe the first functional bioactivity of terebrid venom peptides in relation to pain and diet and indicate that Tv1 and Tsu1.1 may, respectively, act as antinociceptive and orexigenic agents. Tv1 and Tsu1.1 are distinct from previously identified venom peptides, expanding the toolkit of peptides that can potentially be used to investigate the physiological mechanisms of pain and diet.

animal behavior and cognition↗

bioRxiv2018

Modern wolves trace their origin to a late Pleistocene expansion from Beringia

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that maintained a wide geographic distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single late Pleistocene population. Both the geographic origin of this ancestral population and how it became widespread remain a mystery. Here we analyzed a large dataset of novel modern and ancient mitochondrial wolf genomes, spanning the last 50,000 years, using a spatially and temporally explicit modeling framework to show that contemporary wolf populations across the globe trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum - a process most likely driven by the significant ecological changes that occurred across the Northern Hemisphere during this period. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore and provides an insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.

evolutionary biology↗

bioRxiv2018

A metapopulation model of the spread of the Devil Facial Tumour Disease predicts the long term collapse of its host but not its extinction

The Devil Facial Tumour Disease (DFTD), a unique case of a transmissible cancer, had a devastating effect on its host, the Tasmanian Devil. Current estimates of its density are at roughly 20% of the pre-disease state, and single-population epidemiological models have predicted the likely extinction of the host. Here we take advantage of extensive surveys across Tasmania providing data on the spatial and temporal spread of DFTD, and investigate the dynamics of this host-pathogen system using a spatial metapopulation model. We first confirm a most likely origin of DFTD in the north-east corner of the island, and then use the inferred dynamics to predict the fate of the species. We find that our medium-term predictions match additional data not used for fitting, and that on the longterm, Tasmanian Devils are predicted to coexist with the tumour. The key process allowing persistence is the repeated reinvasion of extinct patches from neighbouring areas where the disease has flared up and died out, resulting in a dynamic equilibrium with different levels of spatial heterogeneity. However, this dynamic equilibrium is predicted to keep this apex predator at about 9 % of its original density, with possible dramatic effects on the Tasmanian ecosystem.

ecology↗

bioRxiv2016

Neuromodulatory circuit effects on Drosophila feeding behaviour and metabolism

Animals have evolved to maintain homeostasis in a changing external environment by adapting their internal metabolism and feeding behaviour. Metabolism and behaviour are coordinated by neuromodulation; a number of the implicated neuromodulatory systems are homologous between mammals and the vinegar fly, an important neurogenetic model. We investigated whether silencing fly neuromodulatory networks would elicit coordinated changes in feeding, behavioural activity and metabolism. We employed transgenic lines that allowed us to inhibit broad cellular sets of the dopaminergic, serotonergic, octopaminergic, tyraminergic and neuropeptide F systems. The genetically-manipulated animals were assessed for changes in their overt behavioural responses and metabolism by monitoring eleven parameters: activity; climbing ability; individual feeding; group feeding; food discovery; both fed and starved respiration; fed and starved lipid content; and fed/starved body weight. The results from these 55 experiments indicate that individual neuromodulatory system effects on feeding behaviour, motor activity and metabolism are dissociated.

animal behavior and cognition↗