Biology subjects

Frantz, L.

Publications and source records attributed to Frantz, L..

12 recordsLinked to original sources

bioRxiv2026

The Genomic Landscape of Post-Black Death Epidemics in Northern Europe and the Caucasus

One of the most devastating events in human history, the Black Death (c.1347-1353), marked the beginning of the Second Plague Pandemic. After initially receding, plague returned in intermittent outbreaks throughout Europe, beginning with the pestis secunda. Despite its significance, the post-Black Death epidemiology of Yersinia pestis remains poorly understood. Here, we report 23 new Y. pestis genomes recovered from Second Plague Pandemic contexts across Scandinavia, the Netherlands, Iceland, and Armenia, spanning approximately 270 years. Applying a reproducible mutation-filtering pipeline to assess genetic diversity, we report both Black Death and post-Black Death lineages and document multiple waves of plague at individual cemetery sites. We identify four pestis secunda genomes, including three from Armenia, supporting the eastward dissemination of this lineage prior to its disappearance from Europe. We also resolve a previously under-characterised Branch 1A sub-lineage of Y. pestis and provide the first genomic evidence of plague in Iceland, resolving longstanding uncertainty over its presence on the island. Finally, by calling variants against a reconstructed ancestral reference, we identify clade-defining mutations, including nonsynonymous changes in metabolic and biofilm-related genes with predicted structural effects that may have contributed to shaping the epidemiological dynamics of the Second Plague Pandemic.

genetics↗

bioRxiv2026

The population structure and genetic health of European wolves

Once nearly eradicated from Europe, grey wolves (Canis lupus) have recently undergone a remarkable demographic recovery, but their long-term survival remains precarious. By analyzing 1,001 genomes, we uncover a mosaic of distinct evolutionary lineages, not a single recovering population. Northern populations exhibit Asian wolf ancestry, while southern populations preserve ancient Holocene lineages, with dog introgression varying by region. Isolated wolves from the Scandinavian, Italian, and Iberian peninsulas harbored particularly high levels of inbreeding and fixed deleterious mutations. Signatures of genome erosion were widespread across Europe, with many populations falling well short of the minimum size recommended for long-term survival. Our study reveals the complex tapestry of wolf ancestry and variation across Europe, which calls for nuanced, regional conservation plans founded in genetic monitoring.

genomics↗

bioRxiv2026

The enhanced multi-tissue atlas of regulatory effects in cattle

Cattle are integral to global food security, yet the molecular architecture of their complex traits remains poorly understood. Here, we present the Cattle Genotype-Tissue Expression (CattleGTEx) Phase 1 resource (https://cattlegtex.farmgtex.org/), a substantial expansion of the pilot study. By leveraging 12,422 RNA-seq profiles across 43 tissues and 82 breeds, we characterized 433,972 primary and 161,428 non-primary regulatory effects spanning seven molecular phenotypes. This high-resolution atlas resolves 75% of GWAS signals for 44 complex traits, significantly addressing the "missing regulation" in livestock. We propose a genetic regulatory model demonstrating how variants across multiple biological layers interact with specific biological contexts to shape phenotypic variation. Furthermore, CattleGTEx elucidates mechanisms underlying adaptive evolution between Bos taurus and Bos indicus, as well as artificial selection in dairy and beef breeds. Finally, by mapping evolutionary constraints on these regulatory effects, we demonstrate the translational value of this resource for prioritizing causal variants in human complex diseases. Together, Phase 1 of CattleGTEx provides a transformative framework for functional genomics, precision breeding, and comparative genetics.

genetics↗

bioRxiv2025

Brain size reduction in dogs was already established at least by the Late Neolithic of western Europe, 5,000 years ago

The timing and causes of brain size reduction in domestic dogs remain uncertain. Using endocasts volume as a proxy for brain size, this study provides a first insight into long-term brain size evolution in the wolf-dog lineage. We compared endocranial volumes of 185 modern and 22 prehistoric wolves and dogs ranging from Western Europe to Australia, and spanning the Pleniglacial (35 Ky BP) to the Late Neolithic (5 Ky BP). Our results reveal that Pleistocene so called "protodogs" show no brain size reduction compared to coeval Pleistocene wolves. Instead, we observed a slightly larger relative endocranial volume in the 35,000-year-old protodog from Goyet, which could suggest increased behavioural flexibility in the presence of humans. This hypothesis needs to be tested further. In contrast, Late Neolithic dogs show a drastic 46% brain size reduction with an endocranial volumes comparable to modern small terrier and toy breeds. The anxious and wary temperaments of these Late Neolithic dogs, induced by the brain tissue reorganization associated with such a size reduction, could have served an alerting purpose, among the many other potential roles dogs could have played within this Late Neolithic socio-ecosystems.

zoology↗

bioRxiv2025

An atlas of cell type specific regulatory effects in cattle

Understanding the genetic and molecular architecture of complex traits and artificial selection is crucial for advancing sustainable precision breeding in cattle and other livestock. Yet, how genetic variation affects cellular gene expression remains elusive in cattle. Here, by integrating 8,866 bulk RNA-seq samples and 999,192 single cells of 81 cell types in 22 bovine tissues, we presented a comprehensive atlas of regulatory variants at the cell type resolution in cattle. By colocalizing with bulk-tissue expression quantitative trait loci (beQTL), we detected 57,043 novel cell-type stratified eQTL and cell-type/state interaction eQTL in 18,153 genes, which also exhibited a stronger tissue/cell-type specificity than beQTL. By examining genome-wide associations (GWAS) of 44 complex traits, these cell-resolved eQTL were colocalized with 505 (24%) additional GWAS loci compared to beQTL. Through integrating this resource with selection signatures between dairy and beef cattle, we provided tissue/cell-specific regulatory insights into cattle breeding. Overall, the current atlas of cell-type-specific regulatory variants will serve as an invaluable resource for cattle genomics and selective breeding.

genetics↗

bioRxiv2024

The importance of small island populations for the long term survival of endangered large-bodied insular mammals

Island populations of large vertebrates have experienced higher extinction rates than mainland populations over long timescales due to demographic stochasticity, genetic drift and inbreeding. Conversely, small island populations often experience relatively less anthropogenic habitat degradation than populations on larger islands, making them potential targets for conservation interventions such as genetic rescue to improve their overall genetic diversity. Here we determine the consequences and conservation implications of long-term isolation and recent human activities on genetic diversity of island populations of two forest-dependent mammals endemic to the Wallacea archipelago: the anoa (Bubalus spp.) and babirusa (Babyrousa spp.). Using genomic analyses and habitat suitability models, we show that, compared to closely related species, populations on mainland Sulawesi exhibit low heterozygosity, high inbreeding, and a high proportion of deleterious alleles. In contrast, populations on smaller islands possess fewer deleterious mutations despite exhibiting lower heterozygosity and higher inbreeding. Site frequency spectra indicate that these patterns reflect stronger, long-term purging in smaller island populations. Our results thus suggest that conservation efforts should focus on protecting small island habitats and avoiding translocations from mainland populations. This study highlights the crucial role of small offshore islands for the long-term survival of Wallaceas iconic and indigenous mammals in the face of development on the mainland. Significance statementWithin tropical archipelagos, such as the Wallacea biodiversity hotspot, larger islands experience greater resource exploitation compared to smaller ones, highlighting the potential of smaller islands as refuges for conservation. To investigate the genetic health of populations on small islands, we used genomic, occurrence, and environmental data from a system of replicated populations of anoa and babirusa across islands of varying sizes. In contrast to larger islands like Sulawesi, our results demonstrate that smaller offshore islands not only provide higher-quality habitats but also support populations that have efficiently purged harmful mutations. Thus, despite their known vulnerability over geological time-frames, small island populations can provide long term insurance against human-driven extinction and conservation efforts should prioritise habitat management over translocations.

evolutionary biology↗

bioRxiv2023

The ChickenGTEx pilot analysis: a reference of regulatory variants across 28 chicken tissues

Chicken is a valuable model for understanding fundamental biology, vertebrate evolution and diseases, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional impacts of genetic variants. Here, through integrating 7,015 RNA-Seq and 2,869 whole-genome sequence data, the Chicken Genotype- Tissue Expression (ChickenGTEx) project presents the pilot reference of regulatory variants in 28 chicken tissue transcriptomes, including millions of regulatory effects on primary expression (including protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3 untranslated region alternative polyadenylation). We explored the tissue-sharing and context-specificity of these regulatory variants, their underlying molecular mechanisms of action, and their utility in interpreting adaptation and genome-wide associations of 108 chicken complex traits. Finally, we illustrated shared and lineage-specific features of gene regulation between chickens and mammals, and demonstrated how the ChickenGTEx resource can further assist with translating genetic findings across species. One-Sentence SummaryThe ChickenGTEx provides a multi-tissue reference of regulatory variants for chicken genetics and genomics, functional genomics, precision breeding, veterinary medicine, vertebrate evolution and even human biomedicine.

genetics↗

bioRxiv2022

Genomes of the extinct Sicilian wolf reveal a complex history of isolation and admixture with ancient dogs

The Sicilian wolf represented the only population of wolves living on a Mediterranean island until the first half of the twentieth century (1930s-1960s) 1-7. Previous studies hypothesised that they remained isolated from mainland wolves from the end of the Last Glacial Maximum (LGM) 8,9, until human persecutions led them to extinction 1-7. There are only seven known Sicilian wolf specimens from the 19th and 20th century preserved in museums in Italy and recent morphometric analyses assigned them to the new subspecies Canis lupus cristaldii 10. To better understand the origins of the Sicilian wolf, and its relationship to other wolf populations, we sequenced four whole genomes (3.8x-11.6x) and five mitogenomes. We investigated the relationship between Sicilian wolves and other modern breeds to identify potential admixture. Furthermore, considering that the last land-bridge between Sicily and Italy disappeared after the LGM 11, around 17 kya, we explored the possibility that the Sicilian wolf retained ancestry from ancient wolf and dog lineages. Additionally, we explored whether the long-term isolation might have affected the genomic diversity, inbreeding levels and genetic load of the Sicilian wolf. Our findings show that the Sicilian wolves shared most ancestry with the modern Italian wolf population but are better modelled as admixed with European dog breeds, and shared traces of Eneolithic and Bronze age European dogs. We also find signatures of severe inbreeding and low genomic diversity at population and individual levels due to long-term isolation and drift, suggesting also low effective population size.

genomics↗

bioRxiv2022

ifCNV: a novel isolation-forest-based package to detect copy number variations from NGS datasets

Copy number variations (CNVs) are an essential component of genetic variation distributed across large parts of the human genome. CNV detection from next-generation sequencing data and artificial intelligence algorithms has progressed in recent years. However, only a few tools have taken advantage of machine learning algorithms for CNV detection, and none propose using artificial intelligence to automatically detect probable CNV-positive samples. Furthermore, in general, most CNV software that is developed for specific data types has sub-optimal reliability for routine practice. In addition, the most developed approach is to use a reference or normal dataset to compare with the samples of interest, and it is well known that selecting appropriate normal samples represents a challenging task which dramatically influences the precision of results in all CNV-detecting tools. With careful consideration of these issues, we propose here ifCNV, a new software based on isolation forests that creates its own reference, available in R and python with customisable parameters. ifCNV combines artificial intelligence using two isolation forests and a comprehensive scoring method to faithfully detect CNVs among various samples. It was validated using datasets from diverse origins (capture and amplicon, germline and somatic), and it exhibits high sensitivity, specificity and accuracy. ifCNV is a publicly available open-source software that allows the detection of CNVs in many clinical situations. Key pointsO_LICopy number variation detection C_LIO_LIMachine learning C_LIO_LILocalisation scoring C_LIO_LIBenchmark on various clinical situations and on various datasets C_LIO_LIEasy-to-use R and Python open-source Package C_LI

bioinformatics↗

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

Predicting the viability of archaic human hybrids using a mitochondrial proxy

Ancient DNA evidence has confirmed hybridization between humans and Neanderthals and revealed a complex pattern of admixture between hominin lineages. Many segments of the modern human genome are devoid of Neanderthal ancestry, however, and this non-random distribution has raised questions regarding the frequency and success of hybridisation between ancient human lineages. Here, we examine the hypothesis that hominin hybrid offspring suffered a reduction in fertility by comparing patterns of sequence divergence of mitochondrial and nuclear DNA from numerous hybridising pairs of mammals. Our results reveal a threshold separating species pairs whose divergence values fall within two categories: those whose hybrid offspring can successfully reproduce without backcrossing with their parent species, and those whose hybrid offspring cannot. Using this framework, we predict that the potential hybrid offspring of Neanderthals, Denisovans, the ancient individuals from the Sima de los Huesos and anatomically modern humans would not have suffered a reduction in fertility.

evolutionary biology↗

bioRxiv2018

Synchronous diversification of Sulawesi’s iconic artiodactyls driven by recent geological events

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back 40 Myr ago. Recent studies, however, suggest that much of Sulawesis fauna assembled over the last 15 Myr. Here, we test the hypothesis that recent uplift of previously submerged portions of land on Sulawesi promoted diversification, and that much of the its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric data sets derived from Sulawesis three largest mammals: the Babirusa, Anoa, and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Myr ago to 2-3 Myr ago), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that recent emergence of land on Sulawesi (~1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicates that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.

evolutionary biology↗