@article{14683,
abstract = {Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.
For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1},
author = {Amberg, Nicole and Cheung, Giselle T and Hippenmeyer, Simon},
issn = {2666-1667},
journal = {STAR Protocols},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Neuroscience},
number = {1},
publisher = {Elsevier},
title = {{Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry}},
doi = {10.1016/j.xpro.2023.102771},
volume = {5},
year = {2024},
}
@article{14826,
abstract = {The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.},
author = {Kuhn, Andre and Roosjen, Mark and Mutte, Sumanth and Dubey, Shiv Mani and Carrillo Carrasco, Vanessa Polet and Boeren, Sjef and Monzer, Aline and Koehorst, Jasper and Kohchi, Takayuki and Nishihama, Ryuichi and Fendrych, Matyas and Sprakel, Joris and Friml, Jiří and Weijers, Dolf},
issn = {1097-4172},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
pages = {130--148.e17},
publisher = {Elsevier},
title = {{RAF-like protein kinases mediate a deeply conserved, rapid auxin response}},
doi = {10.1016/j.cell.2023.11.021},
volume = {187},
year = {2024},
}
@article{15033,
abstract = {The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in gn knockouts. The functional GN mutant variant GNfewerroots, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.},
author = {Adamowski, Maciek and Matijevic, Ivana and Friml, Jiří},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery}},
doi = {10.7554/elife.68993},
volume = {13},
year = {2024},
}
@article{15257,
abstract = {Root gravitropic bending represents a fundamental aspect of terrestrial plant physiology. Gravity is perceived by sedimentation of starch-rich plastids (statoliths) to the bottom of the central root cap cells. Following gravity perception, intercellular auxin transport is redirected downwards leading to an asymmetric auxin accumulation at the lower root side causing inhibition of cell expansion, ultimately resulting in downwards bending. How gravity-induced statoliths repositioning is translated into asymmetric auxin distribution remains unclear despite PIN auxin efflux carriers and the Negative Gravitropic Response of roots (NGR) proteins polarize along statolith sedimentation, thus providing a plausible mechanism for auxin flow redirection. In this study, using a functional NGR1-GFP construct, we visualized the NGR1 localization on the statolith surface and plasma membrane (PM) domains in close proximity to the statoliths, correlating with their movements. We determined that NGR1 binding to these PM domains is indispensable for NGR1 functionality and relies on cysteine acylation and adjacent polybasic regions as well as on lipid and sterol PM composition. Detailed timing of the early events following graviperception suggested that both NGR1 repolarization and initial auxin asymmetry precede the visible PIN3 polarization. This discrepancy motivated us to unveil a rapid, NGR-dependent translocation of PIN-activating AGCVIII kinase D6PK towards lower PMs of gravity-perceiving cells, thus providing an attractive model for rapid redirection of auxin fluxes following gravistimulation.},
author = {Kulich, Ivan and Schmid, Julia and Teplova, Anastasiia and Qi, Linlin and Friml, Jiří},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism}},
doi = {10.7554/elife.91523},
volume = {12},
year = {2024},
}
@article{12158,
abstract = {Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.},
author = {Zeller, Peter and Yeung, Jake and Viñas Gaza, Helena and de Barbanson, Buys Anton and Bhardwaj, Vivek and Florescu, Maria and van der Linden, Reinier and van Oudenaarden, Alexander},
issn = {1546-1718},
journal = {Nature Genetics},
keywords = {Genetics},
pages = {333--345},
publisher = {Springer Nature},
title = {{Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis}},
doi = {10.1038/s41588-022-01260-3},
volume = {55},
year = {2023},
}
@article{12163,
abstract = {Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.},
author = {Loose, Martin and Auer, Albert and Brognara, Gabriel and Budiman, Hanifatul R and Kowalski, Lukasz M and Matijevic, Ivana},
issn = {1873-3468},
journal = {FEBS Letters},
keywords = {Cell Biology, Genetics, Molecular Biology, Biochemistry, Structural Biology, Biophysics},
number = {6},
pages = {762--777},
publisher = {Wiley},
title = {{In vitro reconstitution of small GTPase regulation}},
doi = {10.1002/1873-3468.14540},
volume = {597},
year = {2023},
}
@article{12166,
abstract = {Kerstin Johannesson is a marine ecologist and evolutionary biologist based at the Tjärnö Marine Laboratory of the University of Gothenburg, which is situated in the beautiful Kosterhavet National Park on the Swedish west coast. Her work, using marine periwinkles (especially Littorina saxatilis and L. fabalis) as main model systems, has made a remarkable contribution to marine evolutionary biology and our understanding of local adaptation and its genetic underpinnings.},
author = {Westram, Anja M and Butlin, Roger},
issn = {1365-294X},
journal = {Molecular Ecology},
keywords = {Genetics, Ecology, Evolution, Behavior and Systematics},
number = {1},
pages = {26--29},
publisher = {Wiley},
title = {{Professor Kerstin Johannesson–winner of the 2022 Molecular Ecology Prize}},
doi = {10.1111/mec.16779},
volume = {32},
year = {2023},
}
@article{13989,
abstract = {Characterizing and controlling entanglement in quantum materials is crucial for the development of next-generation quantum technologies. However, defining a quantifiable figure of merit for entanglement in macroscopic solids is theoretically and experimentally challenging. At equilibrium the presence of entanglement can be diagnosed by extracting entanglement witnesses from spectroscopic observables and a nonequilibrium extension of this method could lead to the discovery of novel dynamical phenomena. Here, we propose a systematic approach to quantify the time-dependent quantum Fisher information and entanglement depth of transient states of quantum materials with time-resolved resonant inelastic x-ray scattering. Using a quarter-filled extended Hubbard model as an example, we benchmark the efficiency of this approach and predict a light-enhanced many-body entanglement due to the proximity to a phase boundary. Our work sets the stage for experimentally witnessing and controlling entanglement in light-driven quantum materials via ultrafast spectroscopic measurements.},
author = {Hales, Jordyn and Bajpai, Utkarsh and Liu, Tongtong and Baykusheva, Denitsa Rangelova and Li, Mingda and Mitrano, Matteo and Wang, Yao},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering}},
doi = {10.1038/s41467-023-38540-3},
volume = {14},
year = {2023},
}
@article{14077,
abstract = {The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed
so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues
and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila
melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate
crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand,
testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that
have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation
of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression
and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis
variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary
expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance
as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled
experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns.},
author = {Puixeu Sala, Gemma and Macon, Ariana and Vicoso, Beatriz},
issn = {2160-1836},
journal = {G3: Genes, Genomes, Genetics},
keywords = {Genetics (clinical), Genetics, Molecular Biology},
number = {8},
publisher = {Oxford University Press},
title = {{Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster}},
doi = {10.1093/g3journal/jkad121},
volume = {13},
year = {2023},
}
@article{14368,
abstract = {Purpose:
Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype but with limited neuroradiological data and insufficient evidence for causality of the variants.
Methods:
Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays and a zebrafish model.
Results:
We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model.
Conclusion:
We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity.},
author = {Accogli, Andrea and Lin, Sheng-Jia and Severino, Mariasavina and Kim, Sung-Hoon and Huang, Kevin and Rocca, Clarissa and Landsverk, Megan and Zaki, Maha S. and Al-Maawali, Almundher and Srinivasan, Varunvenkat M. and Al-Thihli, Khalid and Schaefer, G. Bradly and Davis, Monica and Tonduti, Davide and Doneda, Chiara and Marten, Lara M. and Mühlhausen, Chris and Gomez, Maria and Lamantea, Eleonora and Mena, Rafael and Nizon, Mathilde and Procaccio, Vincent and Begtrup, Amber and Telegrafi, Aida and Cui, Hong and Schulz, Heidi L. and Mohr, Julia and Biskup, Saskia and Loos, Mariana Amina and Aráoz, Hilda Verónica and Salpietro, Vincenzo and Keppen, Laura Davis and Chitre, Manali and Petree, Cassidy and Raymond, Lucy and Vogt, Julie and Sawyer, Lindsey B. and Basinger, Alice A. and Pedersen, Signe Vandal and Pearson, Toni S. and Grange, Dorothy K. and Lingappa, Lokesh and McDunnah, Paige and Horvath, Rita and Cognè, Benjamin and Isidor, Bertrand and Hahn, Andreas and Gripp, Karen W. and Jafarnejad, Seyed Mehdi and Østergaard, Elsebet and Prada, Carlos E. and Ghezzi, Daniele and Gowda, Vykuntaraju K. and Taylor, Robert W. and Sonenberg, Nahum and Houlden, Henry and Sissler, Marie and Varshney, Gaurav K. and Maroofian, Reza},
issn = {1098-3600},
journal = {Genetics in Medicine},
keywords = {Genetics (clinical)},
number = {11},
publisher = {Elsevier},
title = {{Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder}},
doi = {10.1016/j.gim.2023.100938},
volume = {25},
year = {2023},
}
@article{14639,
abstract = {Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship.
Methods: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity.
Results: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy.
Conclusions: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as “OGDHL-related disorders”.},
author = {Lin, Sheng-Jia and Vona, Barbara and Lau, Tracy and Huang, Kevin and Zaki, Maha S. and Aldeen, Huda Shujaa and Karimiani, Ehsan Ghayoor and Rocca, Clarissa and Noureldeen, Mahmoud M. and Saad, Ahmed K. and Petree, Cassidy and Bartolomaeus, Tobias and Abou Jamra, Rami and Zifarelli, Giovanni and Gotkhindikar, Aditi and Wentzensen, Ingrid M. and Liao, Mingjuan and Cork, Emalyn Elise and Varshney, Pratishtha and Hashemi, Narges and Mohammadi, Mohammad Hasan and Rad, Aboulfazl and Neira, Juanita and Toosi, Mehran Beiraghi and Knopp, Cordula and Kurth, Ingo and Challman, Thomas D. and Smith, Rebecca and Abdalla, Asmahan and Haaf, Thomas and Suri, Mohnish and Joshi, Manali and Chung, Wendy K. and Moreno-De-Luca, Andres and Houlden, Henry and Maroofian, Reza and Varshney, Gaurav K.},
issn = {1756-994X},
journal = {Genome Medicine},
keywords = {Genetics (clinical), Genetics, Molecular Biology, Molecular Medicine},
publisher = {Springer Nature},
title = {{Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity}},
doi = {10.1186/s13073-023-01258-4},
volume = {15},
year = {2023},
}
@article{14742,
abstract = {Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics.
While an important role for CRs in speciation has been suggested, evidence primarily stems
from theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon
pairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at
a macroevolutionary level has been supported by associations between species diversity and
rates of evolution of CRs across phylogenies, these findings are limited to a restricted range of
CRs and taxa. Now that more broadly applicable and precise CR detection approaches have
become available, we address the challenges in filling some of the conceptual and empirical
gaps between micro- and macroevolutionary studies on the role of CRs in speciation. We
synthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life.},
author = {Lucek, Kay and Giménez, Mabel D. and Joron, Mathieu and Rafajlović, Marina and Searle, Jeremy B. and Walden, Nora and Westram, Anja M and Faria, Rui},
issn = {1943-0264},
journal = {Cold Spring Harbor Perspectives in Biology},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {11},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{The impact of chromosomal rearrangements in speciation: From micro- to macroevolution}},
doi = {10.1101/cshperspect.a041447},
volume = {15},
year = {2023},
}
@misc{12949,
abstract = {The classical infinitesimal model is a simple and robust model for the inheritance of quantitative traits. In this model, a quantitative trait is expressed as the sum of a genetic and a non-genetic (environmental) component and the genetic component of offspring traits within a family follows a normal distribution around the average of the parents’ trait values, and has a variance that is independent of the trait values of the parents. Although the trait distribution across the whole population can be far from normal, the trait distributions within families are normally distributed with a variance-covariance matrix that is determined entirely by that in the ancestral population and the probabilities of identity determined by the pedigree. Moreover, conditioning on some of the trait values within the pedigree has predictable effects on the mean and variance within and between families. In previous work, Barton et al. (2017), we showed that when trait values are determined by the sum of a large number of Mendelian factors, each of small effect, one can justify the infinitesimal model as limit of Mendelian inheritance. It was also shown that under some forms of epistasis, trait values within a family are still normally distributed.},
author = {Barton, Nicholas H},
keywords = {Quantitative genetics, infinitesimal model},
publisher = {Institute of Science and Technology Austria},
title = {{The infinitesimal model with dominance}},
doi = {10.15479/AT:ISTA:12949},
year = {2023},
}
@article{14781,
abstract = {Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency.},
author = {Westerich, Kim Joana and Tarbashevich, Katsiaryna and Schick, Jan and Gupta, Antra and Zhu, Mingzhao and Hull, Kenneth and Romo, Daniel and Zeuschner, Dagmar and Goudarzi, Mohammad and Gross-Thebing, Theresa and Raz, Erez},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {17},
pages = {1578--1592.e5},
publisher = {Elsevier},
title = {{Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1}},
doi = {10.1016/j.devcel.2023.06.009},
volume = {58},
year = {2023},
}
@article{14787,
abstract = {Understanding the phenotypic and genetic architecture of reproductive isolation is a long‐standing goal of speciation research. In several systems, large‐effect loci contributing to barrier phenotypes have been characterized, but such causal connections are rarely known for more complex genetic architectures. In this study, we combine “top‐down” and “bottom‐up” approaches with demographic modelling toward an integrated understanding of speciation across a monkeyflower hybrid zone. Previous work suggests that pollinator visitation acts as a primary barrier to gene flow between two divergent red‐ and yellow‐flowered ecotypes ofMimulus aurantiacus. Several candidate isolating traits and anonymous single nucleotide polymorphism loci under divergent selection have been identified, but their genomic positions remain unknown. Here, we report findings from demographic analyses that indicate this hybrid zone formed by secondary contact, but that subsequent gene flow was restricted by widespread barrier loci across the genome. Using a novel, geographic cline‐based genome scan, we demonstrate that candidate barrier loci are broadly distributed across the genome, rather than mapping to one or a few “islands of speciation.” Quantitative trait locus (QTL) mapping reveals that most floral traits are highly polygenic, with little evidence that QTL colocalize, indicating that most traits are genetically independent. Finally, we find little evidence that QTL and candidate barrier loci overlap, suggesting that some loci contribute to other forms of reproductive isolation. Our findings highlight the challenges of understanding the genetic architecture of reproductive isolation and reveal that barriers to gene flow other than pollinator isolation may play an important role in this system.},
author = {Stankowski, Sean and Chase, Madeline A. and McIntosh, Hanna and Streisfeld, Matthew A.},
issn = {1365-294X},
journal = {Molecular Ecology},
keywords = {Genetics, Ecology, Evolution, Behavior and Systematics},
number = {8},
pages = {2041--2054},
publisher = {Wiley},
title = {{Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone}},
doi = {10.1111/mec.16849},
volume = {32},
year = {2023},
}
@article{12802,
abstract = {Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.},
author = {Knaus, Lisa and Basilico, Bernadette and Malzl, Daniel and Gerykova Bujalkova, Maria and Smogavec, Mateja and Schwarz, Lena A. and Gorkiewicz, Sarah and Amberg, Nicole and Pauler, Florian and Knittl-Frank, Christian and Tassinari, Marianna and Maulide, Nuno and Rülicke, Thomas and Menche, Jörg and Hippenmeyer, Simon and Novarino, Gaia},
issn = {0092-8674},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {9},
pages = {1950--1967.e25},
publisher = {Elsevier},
title = {{Large neutral amino acid levels tune perinatal neuronal excitability and survival}},
doi = {10.1016/j.cell.2023.02.037},
volume = {186},
year = {2023},
}
@article{12521,
abstract = {Differentiated X chromosomes are expected to have higher rates of adaptive divergence than autosomes, if new beneficial mutations are recessive (the “faster-X effect”), largely because these mutations are immediately exposed to selection in males. The evolution of X chromosomes after they stop recombining in males, but before they become hemizygous, has not been well explored theoretically. We use the diffusion approximation to infer substitution rates of beneficial and deleterious mutations under such a scenario. Our results show that selection is less efficient on diploid X loci than on autosomal and hemizygous X loci under a wide range of parameters. This “slower-X” effect is stronger for genes affecting primarily (or only) male fitness, and for sexually antagonistic genes. These unusual dynamics suggest that some of the peculiar features of X chromosomes, such as the differential accumulation of genes with sex-specific functions, may start arising earlier than previously appreciated.},
author = {Mrnjavac, Andrea and Khudiakova, Kseniia and Barton, Nicholas H and Vicoso, Beatriz},
issn = {2056-3744},
journal = {Evolution Letters},
keywords = {Genetics, Ecology, Evolution, Behavior and Systematics},
number = {1},
publisher = {Oxford University Press},
title = {{Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution}},
doi = {10.1093/evlett/qrac004},
volume = {7},
year = {2023},
}
@article{12159,
abstract = {The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relationship between haplotype blocks and ancestral structure, emphasizing the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical data set. While the advent of new, computationally efficient methods makes it possible to apply these concepts broadly, they (and additional new methods) could benefit from adding features to explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.},
author = {Shipilina, Daria and Pal, Arka and Stankowski, Sean and Chan, Yingguang Frank and Barton, Nicholas H},
issn = {1365-294X},
journal = {Molecular Ecology},
keywords = {Genetics, Ecology, Evolution, Behavior and Systematics},
number = {6},
pages = {1441--1457},
publisher = {Wiley},
title = {{On the origin and structure of haplotype blocks}},
doi = {10.1111/mec.16793},
volume = {32},
year = {2023},
}
@article{14613,
abstract = {Many insects carry an ancient X chromosome - the Drosophila Muller element F - that likely predates their origin. Interestingly, the X has undergone turnover in multiple fly species (Diptera) after being conserved for more than 450 MY. The long evolutionary distance between Diptera and other sequenced insect clades makes it difficult to infer what could have contributed to this sudden increase in rate of turnover. Here, we produce the first genome and transcriptome of a long overlooked sister-order to Diptera: Mecoptera. We compare the scorpionfly Panorpa cognata X-chromosome gene content, expression, and structure, to that of several dipteran species as well as more distantly-related insect orders (Orthoptera and Blattodea). We find high conservation of gene content between the mecopteran X and the dipteran Muller F element, as well as several shared biological features, such as the presence of dosage compensation and a low amount of genetic diversity, consistent with a low recombination rate. However, the two homologous X chromosomes differ strikingly in their size and number of genes they carry. Our results therefore support a common ancestry of the mecopteran and ancestral dipteran X chromosomes, and suggest that Muller element F shrank in size and gene content after the split of Diptera and Mecoptera, which may have contributed to its turnover in dipteran insects.},
author = {Lasne, Clementine and Elkrewi, Marwan N and Toups, Melissa A and Layana Franco, Lorena Alexandra and Macon, Ariana and Vicoso, Beatriz},
issn = {1537-1719},
journal = {Molecular Biology and Evolution},
keywords = {Genetics, Molecular Biology, Ecology, Evolution, Behavior and Systematics},
number = {12},
publisher = {Oxford University Press},
title = {{The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome}},
doi = {10.1093/molbev/msad245},
volume = {40},
year = {2023},
}
@article{11447,
abstract = {Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.},
author = {Saona Urmeneta, Raimundo J and Kondrashov, Fyodor and Khudiakova, Kseniia},
issn = {1522-9602},
journal = {Bulletin of Mathematical Biology},
keywords = {Computational Theory and Mathematics, General Agricultural and Biological Sciences, Pharmacology, General Environmental Science, General Biochemistry, Genetics and Molecular Biology, General Mathematics, Immunology, General Neuroscience},
number = {8},
publisher = {Springer Nature},
title = {{Relation between the number of peaks and the number of reciprocal sign epistatic interactions}},
doi = {10.1007/s11538-022-01029-z},
volume = {84},
year = {2022},
}