Biology subjects

Le Goff, M.

Publications and source records attributed to Le Goff, M..

6 recordsLinked to original sources

bioRxiv2026

Adaptive introgression in subdivided populations leaves distinct genomic footprints under global and local selection: a case study in Ciona intestinalis

Adaptive introgression, the transfer of beneficial alleles between species through hybridization, is increasingly recognized as an important source of adaptation to novel environments. However, the theory of adaptive introgression has primarily been developed for a single panmictic population, whereas many empirical examples involve spatially subdivided populations. In such systems, a low-frequency adaptive allele may either represent the leading edge of an adaptive travelling wave or occur in a subpopulation where the introgressed allele is locally selected against. We developed a simple prediction based on the relationship between adaptive allele frequency and introgressed tract length. Simulations predict a positive correlation during an ongoing sweep of an unconditionally beneficial allele, but no correlation under local adaptation. Tract erosion provides a recombination clock for time since introgression, which also determines the distance travelled by the adaptive wave and hence allele frequency in the former, whereas allele frequency is determined by local selection in the latter. We tested this prediction in a well-characterized case of adaptive introgression, in the sea squirt Ciona intestinalis, using haplotagging to reconstruct phased genomes and local ancestry. We found no relationship between adaptive allele frequency and introgressed tract length, providing additional support for a model of local adaptation rather than ongoing global selective sweep.

genetics↗

bioRxiv2026

A 23-copy tandem repeat of a cytochrome P450 gene underlies an adaptive introgression breakthrough in Ciona intestinalis

Introgression between highly divergent species is generally selected against, yet some foreign alleles can break through species barriers when they provide a sufficient selective advantage, a process known as adaptive introgression. Here, we characterize the structural variant underlying adaptive introgression from Ciona robusta into C. intestinalis, two species separated by 14.5% net molecular divergence. Previous work identified a narrow peak of C. robusta ancestry on chromosome 5 that reached high frequency in several C. intestinalis populations despite otherwise restricted introgression. Using whole-genome Nanopore sequences from 15 C. intestinalis and three C. robusta individuals, together with short-read datasets including parent-offspring trios, we narrowed down the core introgressed segment from 16 to three genes and characterized copy-number variation affecting the cytochrome P450 gene CYP2U1c. The introgressed haplotype carries a tandem amplification of a 5,173-bp segment containing CYP2U1c, with 23 consecutive copies and conserved repeat boundaries. The nearly 120-kb array could not be fully resolved by long-read sequencing, but coverage consistently supported approximately 23 copies per introgressed haplotype. Despite its extreme size and repetitive structure, the allele showed Mendelian inheritance. CYP2U1c copy number was also polymorphic in C. robusta. Long reads fully resolved two structurally distinct haplotypes in one individual, carrying either a duplication encompassing adjacent CYP2U1b and CYP2U1c genes or five CYP2U1c copies. Their distinct breakpoints indicate independent origins. Our results reveal independently arising CYP2U1c amplifications in the donor species and show that an extreme high-copy-number allele was subsequently favoured following introgression into C. intestinalis.

evolutionary biology↗

bioRxiv2026

Interplay of NuA4/TIP60 and PRC2 Complex Activities in Fusion Driven Endometrial Stromal Sarcoma

Low-grade endometrial stromal sarcoma (LGESS) exhibits frequent chromosomal translocations that fuse various subunits of the NuA4/TIP60 co-activator complex to subunits of the Polycomb Repressive Complex 2 (PRC2) complex. LGESS fusion proteins, such as the commonly occurring JAZF1-SUZ12, have been shown to upregulate genes through mislocalization of NuA4/TIP60 activity to Polycomb target genes. In this study, we characterized an interesting recurrent fusion protein in LGESS that fused a NuA4/TIP60 component, MBTD1, to EZHIP. EZHIP is a recently described vertebrate protein that enzymatically inhibits methyltransferase activity of the PRC2 complex and is a potent oncogene. The MBTD1-EZHIP fusion protein forms a chimeric TIP60-PRC2.1 complex and drastically reduces H3K27me3 levels at Polycomb target genes, similar to EZHIP-overexpressing cancers. However, unlike EZHIP overexpression, MBTD1-EZHIP requires mislocalization of NuA4/TIP60 activity through the MBTD1 protein to upregulate oncogenes. Despite differences in the finer molecular mechanisms, MBTD1-EZHIP and the common JAZF1-SUZ12 fusion protein upregulated similar sets of genes in cell lines, showing a convergence of oncogenic gene expression. Surprisingly, unlike in cellular models, JAZF1-SUZ12 translocated patient samples showed not only upregulation of genes driven by increased H4K8ac and decreased H3K27me3 but also downregulation of specific genes due to accumulated H3K27me3, revealing an additional oncogenic mechanism in LGESS.

cancer biology↗

bioRxiv2022

Environmental, social, and morphological drivers of fission-fusion dynamics in a social ungulate

Social groups exist because individuals within the group accrue a net benefit from sharing space. The profitability of sociality, however, varies with ecological context. As ecological context varies, tension emerges among the costs and benefits of social grouping. Fission-fusion societies are fluid in their group dynamics across spatial and temporal contexts, permitting insights into how context affects whether animals choose to join or depart a group. We tested four non-mutually exclusive hypotheses driving variation in fission and fusion in caribou: the risky places, environment heterogeneity, activity budget, and social familiarity hypotheses. The risky places hypothesis predicts animals are unlikely to diffuse when habitats are open and risk of predation is elevated. The habitat heterogeneity hypothesis predicts that fission is more likely in a heterogeneous landscape due to the rising conflicts of interest between group members. The activity budget hypothesis predicts dyads associate by body size due to similar food passage rates. The social cohesion hypothesis predicts that familiar individuals are less likely to fission. We tested the hypotheses using time-to-event (time before fission) analyses and a linear model that assesses spatial, social, and body size relationships among female caribou (n = 22) on Fogo Island, Newfoundland, Canada. Contrary to our prediction for risky places, probability of fission was not influenced by habitat openness. The hypothesis of environmental heterogeneity was partially supported, as caribou remained less cohesive in environments with a higher richness of habitats. No direct evidence emerged to support the activity budget hypothesis. However, it appears that caribou maintain the strongest social bonds among variably sized individuals and these social bonds do decrease the propensity to split. Collectively, our findings showed that social interactions may depend not only on individual identity and characteristics, but also the spatial context in which these interactions occur.

animal behavior and cognition↗

bioRxiv2018

Confinement-induced transition between wave-like collective cell migration modes

The structural and functional organization of biological tissues relies on the intricate interplay between chemical and mechanical signaling. Whereas the role of constant and transient mechanical perturbations is generally accepted, several studies recently highlighted the existence of long-range mechanical excitations (i.e., waves) at the supracellular level. Here, we confine epithelial cell mono-layers to quasi-one dimensional geometries, to force the establishment of tissue-level waves of well-defined wavelength and period. Numerical simulations based on a self-propelled Voronoi model reproduce the observed waves and exhibit a phase transition between a global and a multi-nodal wave, controlled by the confinement size. We confirm experimentally the existence of such a phase transition, and show that wavelength and period are independent of the confinement length. Together, these results demonstrate the intrinsic origin of tissue oscillations, which could provide cells with a mechanism to accurately measure distances at the supracellular level.

biophysics↗

bioRxiv2018

Extracellular Matrix acts as pressure detector in biological tissues

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1-5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6-8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9-13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.

biophysics↗