scholarly journals Oncogenic allelic interaction inXiphophorushighlights hybrid incompatibility

2020 ◽  
Vol 117 (47) ◽  
pp. 29786-29794
Author(s):  
Yuan Lu ◽  
Angel Sandoval ◽  
Sarah Voss ◽  
Zhao Lai ◽  
Susanne Kneitz ◽  
...  
Keyword(s):  
Single Gene ◽  
Growth Factor Receptor ◽  
Cancer Etiology ◽  
Hybrid Incompatibility ◽  
Interspecies Hybridization ◽  
Species Population ◽  
Active Research ◽  
Progeny Ratio ◽  
Allelic Interaction ◽  
Species Specific

Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails leads to lethal melanocyte tumorigenesis. This occurs in hybrids with tumor incidence following progeny ratio that is consistent with two-locus interaction, suggesting melanoma development is a result of negative epistasis. Such observations makeXiphophorusone of the only two vertebrate hybrid incompatibility examples in which interacting genes have been identified. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over five decades of active research. Here we report the localization of the melanoma regulatory locus to a single gene,rab3d, which shows all expected features of the long-sought oncogene interacting locus. Our findings provide insights into the role ofegfrregulation in regard to cancer etiology. Finally, they provide a molecular explainable example of hybrid incompatibility.

scholarly journals A Case Report of Primary Resistance to EGFR TKI in Lung Adenocarcinoma Due to Coexisting MET Exon 14 Skipping Mutation with Excellent Response to Combination of Gefitinib and Capmatinib

2021 ◽  
Author(s):  
Nirmal Vivek Raut ◽  
Siddharth Srivastava ◽  
Guarav Dilip Gangwani ◽  
Heena Sajid Ali
Keyword(s):  
Kinase Inhibitors ◽  
Single Gene ◽  
Growth Factor Receptor ◽  
Nonsmall Cell Lung Cancer ◽  
Primary Resistance ◽  
Gene Testing ◽  
Comprehensive Genomic Profiling ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Next Generation Sequencing Ngs ◽  
Egfr Tki

AbstractTreatment of nonsmall cell lung cancer (NSCLC) carrying an epidermal growth factor receptor (EGFR) mutation depends on EGFR tyrosine kinase inhibitors (TKIs). However, all patients treated with EGFR TKI eventually develop progressive disease. Approximately, 20% of patients do not respond to EGFR TKIs, which is defined as primary resistance. The prognosis of these patients is similar to NSCLC with nondriver mutations. We report a case of a patient with EGFR exon 21 mutation who rapidly progressed in 15 days on Gefitinib. Next-generation sequencing (NGS) showed a MET exon 14 skip mutation coexisting with EGFR exon 21 mutation, causing primary resistance to EGFR TKI. Based on NGS reports, a treatment combining Gefitinib and Capmatinib, a MET inhibitor, induced a rapid response in the patient, which was sustained at the end of 8 months. This clearly emphasizes the need for comprehensive genomic profiling using NGS over single gene testing.

scholarly journals Genome-wide markers reveal differentiation between and within the cryptic sister species, sunset and vermilion rockfish

2021 ◽  
Author(s):  
Gary C. Longo ◽  
John Harms ◽  
John R. Hyde ◽  
Matthew T. Craig ◽  
Ana Ramón-Laca ◽  
...  
Keyword(s):  
Management Strategies ◽  
Cost Effective ◽  
Sister Species ◽  
Nucleotide Polymorphisms ◽  
Relative Contribution ◽  
Genetic Groups ◽  
Cost Effective Method ◽  
Species Population ◽  
Single Complex ◽  
Species Specific

AbstractThe vermilion rockfish complex, which consists of the cryptic sister species vermilion and sunset rockfish, is one of the most valuable recreational fisheries on the U.S. West Coast. These species are currently managed as a single complex, and because of uncertainty surrounding the relative contribution of each species within existing data sources, the stock status of each species is not fully known. A reliable and cost-effective method is needed to disentangle these species that will allow for the development of abundance indices, life history profiles, and catch histories that may potentially support species-specific stock assessments. Using restriction-site associated DNA sequence (RADseq) markers we generated 10,003 polymorphic loci to characterize the vermilion rockfish complex. PCA and Bayesian clustering approaches based on these loci clearly distinguished between sunset and vermilion rockfishes and identified hybrid individuals. These loci included 203 highly differentiated (FST ≥ 0.99) single nucleotide polymorphisms, which we consider candidates in the planned development of a diagnostic assay capable of distinguishing between these cryptic species. In addition to clearly delineating to species, subsets of the interspecific markers allowed for insight into intraspecific differentiation in both species. Population genetic analyses for sunset rockfish identified two weakly divergent genetic groups with similar levels of genetic diversity. Vermilion rockfish, however, were characterized by three distinct genetic groups with much stronger signals of differentiation and significantly different genetic diversities. Collectively, these data will contribute to well-informed, species-specific management strategies to protect this valuable species complex.

scholarly journals Why and how might genetic and phylogenetic diversity be reflected in the identification of key biodiversity areas?

2015 ◽  
Vol 370 (1662) ◽  
pp. 20140019 ◽  
Author(s):  
T. M. Brooks ◽  
A. Cuttelod ◽  
D. P. Faith ◽  
J. Garcia-Moreno ◽  
P. Langhammer ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Threatened Species ◽  
Phylogenetic Diversity ◽  
Species Population ◽  
Threatened Taxa ◽  
Conservation Actions ◽  
Ecosystem Diversity ◽  
Species Specific ◽  
A Site ◽  
Specific Conservation

‘Key biodiversity areas' are defined as sites contributing significantly to the global persistence of biodiversity. The identification of these sites builds from existing approaches based on measures of species and ecosystem diversity and process. Here, we therefore build from the work of Sgró et al. (2011 Evol. Appl. 4 , 326–337. ( doi:10.1111/j.1752-4571.2010.00157.x )) to extend a framework for how components of genetic diversity might be considered in the identification of key biodiversity areas. We make three recommendations to inform the ongoing process of consolidating a key biodiversity areas standard: (i) thresholds for the threatened species criterion currently consider a site's share of a threatened species' population; expand these to include the proportion of the species' genetic diversity unique to a site; (ii) expand criterion for ‘threatened species' to consider ‘threatened taxa’ and (iii) expand the centre of endemism criterion to identify as key biodiversity areas those sites holding a threshold proportion of the compositional or phylogenetic diversity of species (within a taxonomic group) whose restricted ranges collectively define a centre of endemism. We also recommend consideration of occurrence of EDGE species (i.e. threatened phylogenetic diversity) in key biodiversity areas to prioritize species-specific conservation actions among sites.

Sexual Selection, Timing and an X–Y Homologous Gene: Did Homo Sapiens Speciate on the Y Chromosome?

2004 ◽  
Author(s):  
Tim J. Crow
Keyword(s):  
Sexual Selection ◽  
Sex Chromosome ◽  
Homo Sapiens ◽  
Single Gene ◽  
Critical Role ◽  
Hominid Evolution ◽  
Homologous Gene ◽  
Chromosomal Change ◽  
Species Specific ◽  
Sex Chromosome Aneuploidies

This chapter provides a theory of the speciation of modern Homo sapiens, that a single gene played a critical role in the transition from a precursor species. The theory is founded upon the following: firstly, the premise that hemispheric asymmetry is the defining feature of the human brain and the only plausible correlate of language; secondly, an argument for a specific candidate region (the Xq21.3/Yp11.2 region of homology) based upon the reciprocal deficits associated with the sex chromosome aneuploidies, and the course of chromosomal change in hominid evolution; and thirdly, a particular evolutionary mechanism (sexual selection acting on an X-Y-linked gene) to account for species-specific modification of what initially was a saltational change. These postulates relate to the case of modern Homo sapiens. On the basis of the recent literature, the discussion argues that the third premise has general significance as a mechanism of speciation.

Some like it hot? Developmental differences in Yellow-bellied Toad (Bombina variegata) tadpoles from geographically close but different habitats

2016 ◽  
Vol 94 (2) ◽  
pp. 69-77 ◽  
Author(s):  
C. Dittrich ◽  
S. Drakulić ◽  
M. Schellenberg ◽  
J. Thein ◽  
M.-O. Rödel
Keyword(s):  
Body Condition ◽  
Common Garden ◽  
Developmental Time ◽  
Climatic Conditions ◽  
Developmental Differences ◽  
Future Climate Change ◽  
Term Survival ◽  
Species Population ◽  
Bombina Variegata ◽  
Species Specific

The key for the long-term survival of species is their potential to respond to changing conditions. These reactions are usually species-specific and may vary between populations. The Yellow-bellied Toad (Bombina variegata (L., 1758)) occurs in forested and open areas. We wanted to know whether tadpoles react plastically to different environmental conditions, and if so, whether reaction norms are species, population, or season specific. In a common garden experiment, we compared developmental traits (developmental time, size, body condition) of metamorphs from different habitats (forest vs. quarry) in close geographic proximity. Tadpoles from both habitats grew up under shaded and sunny conditions. The experiments were run during early and late breeding season. We detected different developmental strategies between populations, concerning treatments and season on a microgeographic scale. Tadpoles with quarry origin developed faster and reached larger body sizes, at the expense of lower body condition. Major risks affecting tadpole’s survival in the open habitat are high temperatures and high desiccation. Forest tadpoles were comparatively smaller in size, but showed higher plasticity and higher body condition. Under changing climatic conditions, quarry population may reach temperatures above their thermal limits. In contrast, forest conditions may mitigate increasing temperatures. Forest populations could be better adapted to future climate change.

scholarly journals Hybrid seed incompatibility in Capsella is connected to chromatin condensation defects in the endosperm

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009370
Author(s):  
Katarzyna Dziasek ◽  
Lauriane Simon ◽  
Clément Lafon-Placette ◽  
Benjamin Laenen ◽  
Cecilia Wärdig ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromatin Condensation ◽  
Hybrid Seed ◽  
Closely Related Species ◽  
Single Chromosome ◽  
Hybrid Incompatibility ◽  
Molecular Events ◽  
Interspecies Hybridization ◽  
Capsella Rubella ◽  
Related Plant

Hybridization of closely related plant species is frequently connected to endosperm arrest and seed failure, for reasons that remain to be identified. In this study, we investigated the molecular events accompanying seed failure in hybrids of the closely related species pair Capsella rubella and C. grandiflora. Mapping of QTL for the underlying cause of hybrid incompatibility in Capsella identified three QTL that were close to pericentromeric regions. We investigated whether there are specific changes in heterochromatin associated with interspecific hybridizations and found a strong reduction of chromatin condensation in the endosperm, connected with a strong loss of CHG and CHH methylation and random loss of a single chromosome. Consistent with reduced DNA methylation in the hybrid endosperm, we found a disproportionate deregulation of genes located close to pericentromeric regions, suggesting that reduced DNA methylation allows access of transcription factors to targets located in heterochromatic regions. Since the identified QTL were also associated with pericentromeric regions, we propose that relaxation of heterochromatin in response to interspecies hybridization exposes and activates loci leading to hybrid seed failure.

scholarly journals Copy number networks to guide combinatorial therapy for cancer and other disorders

2014 ◽  
Author(s):  
Andy Lin ◽  
Desmond James Smith
Keyword(s):  
Drug Treatment ◽  
Protein Interactions ◽  
Copy Number ◽  
Genetic Interaction ◽  
Single Gene ◽  
Growth Factor Receptor ◽  
Molecular Networks ◽  
Protein Protein Interactions ◽  
Gene Pairs ◽  
Cancer Networks

The dwindling drug pipeline is driving increased interest in the use of genome datasets to inform drug treatment. In particular, networks based on transcript data and protein-protein interactions have been used to design therapies that employ drug combinations. But there has been less focus on employing human genetic interaction networks constructed from copy number alterations (CNAs). These networks can be charted with sensitivity and precision by seeking gene pairs that tend to be amplified and/or deleted in tandem, even when they are located at a distance on the genome. Our experience with radiation hybrid (RH) panels, a library of cell clones that have been used for genetic mapping, have shown this tool can pinpoint statistically significant patterns of co-inherited gene pairs. In fact, we were able to identify gene pairs specifically associated with the mechanism of cell survival at single gene resolution. The strategy of seeking correlated CNAs can also be used to map survival networks for cancer. Although the cancer networks have lower resolution, the RH network can be leveraged to provide single gene specificity in the tumor networks. In a survival network for glioblastoma possessing single gene resolution, we found that the epidermal growth factor receptor (EGFR) oncogene interacted with 46 genes. Of these genes, ten (22%) happened to be targets for existing drugs. Here, we briefly review the previous use of molecular networks to design novel therapies. We then highlight the potential of using correlated CNAs to guide combinatorial drug treatment in common medical conditions. We focus on therapeutic opportunities in cancer, but also offer examples from autoimmune disorders and atherosclerosis.

scholarly journals A Fasciclin 2 functional switch controls organ size in Drosophila

2018 ◽  
Author(s):  
Emma Velasquez ◽  
Jose A. Gomez-Sanchez ◽  
Emmanuelle Donier ◽  
Carmen Grijota-Martinez ◽  
Hugo Cabedo ◽  
...  
Keyword(s):  
Imaginal Disc ◽  
Growth Factor Receptor ◽  
Tissue Growth ◽  
Organ Size ◽  
Autonomous Function ◽  
Genetic Mosaic ◽  
Binding Partners ◽  
A Cell ◽  
Epidermal Growth ◽  
Species Specific

How cell to cell interactions control local tissue growth to attain a species-specific pattern and organ size is a central question in developmental biology. The Drosophila Neural Cell Adhesion Molecule, Fasciclin 2 (Drosophila NCAM), is expressed during the development of neural and epithelial organs. Genetic mosaic analysis of Fasciclin 2 reveals two complementary and opposing functions during imaginal disc growth, a cell autonomous requirement to promote growth and an opposite non-cell autonomous function to restrain growth at high expression levels. This non-cell autonomous function is mediated by the Fasciclin 2 heterophilic-binding partners CG15630 and CG33543. We show that EGFR physically interacts with Fasciclin 2 and mediates both the cell autonomous and the non-cell autonomous function. We further show that EGFR activity in turn promotes the cell autonomous expression of Fasciclin 2. We suggest that the auto-stimulatory loop between EGFR and Fasciclin 2 operates until reaching a threshold where the Fasciclin 2 non-cell autonomous function counteracts the growth-promoting activity of the homophilic interaction to terminate imaginal disc growth. Accordingly, we have found that Fasciclin 2 limits imaginal disc growth by the end of larval development. Cellular integration of Fasciclin 2 autonomous and non-cell autonomous signaling from neighbor cells may be a key regulator component to orchestrate the rate of intercalary cell proliferation and the final size of an organ.Author SummaryOne of the key unsolved problems in Biology is how a species-specific size is attained during animal development. During development cells should compute the amount of intercalary tissue growth to stop cell proliferation when reaching a correct pattern and size. Classic studies demonstrated that local cell interactions are key in controlling organ growth to reach a correct size and pattern in vertebrates and invertebrates. We present evidence strongly suggesting that Fasciclin 2 (the ortholog of NCAM in Drosophila) functions as a growth level switch to control pattern and organ size. First, we use genetic mosaic analyses to show that Fasciclin 2 promotes organ growth in a cell autonomous manner. Then we show that Fasciclin 2 restrains growth at high expression levels in a non-cell autonomous manner, and that there is a requirement for Fasciclin 2 to limit growth by the end of larval development. This function is dependent on Fasciclin 2 heterophilic binding partners CG15630 and CG33543. The Epidermal Growth Factor receptor mediates both functional facets of Fasciclin 2 and its activity in turn increases Fasciclin 2 cell autonomous expression, suggesting the existence of a functional auto-stimulatory loop. We also show that the Epidermal Growth Factor receptor and Fasciclin 2 physically interact. Our results show that the amount of Fasciclin 2 between cells determines organ size by acting as an expression level switch for EGFR function, and suggest that other specific CAM interactions may integrate similar expression level switches acting as a code for cells to compute local growth in attaining a species-specific organ size and shape.

scholarly journals Plant speciation in the Namib Desert: origin of a widespread derivative species from a narrow endemic

2022 ◽  
Author(s):  
Joseph J Milton ◽  
Matthias Affenzeller ◽  
Richard J Abbott ◽  
Hans-Peter Comes
Keyword(s):  
Single Gene ◽  
Distinct Species ◽  
Plant Evolution ◽  
Dispersal Ability ◽  
North African ◽  
Namib Desert ◽  
Hybrid Incompatibility ◽  
Niche Divergence ◽  
Northward Expansion

Background: Parapatric (or budding) speciation is increasingly recognized as an important phenomenon in plant evolution but its role in extreme (e.g. desert) environments is poorly documented. Aims: To test this speciation model in a hypothesized sister pair, the Southwest and North African disjunct Senecio flavus and its putative progenitor, the Namibian Desert endemic S. englerianus. Methods: Phylogenetic inferences were combined with niche divergence tests, morphometrics, and experimental genetic approaches. We also evaluated the potential role of an African Dry Corridor (ADC) in promoting the hypothesized northward expansion of S. flavus (from Namibia), using palaeodistribution models. Results: Belonging to an isolated (potentially relict) clade, the two morphologically distinct species show pronounced niche divergence in Namibia and signs of digenic epistatic hybrid incompatibility (based on F2 pollen fertility). The presence of connate fluked pappus hairs in S. flavus, likely increasing dispersal ability, is controlled by a single gene locus. Conclusions: Our results provide support for a rare example of budding speciation in which a wider ranged derivative (S. flavus) originated at the periphery of a smaller ranged progenitor (S. englerianus) in the Namib Desert region. The Southwest and North African disjunction of S. flavus could have been established by dispersal across intermediate ADC areas during periods of (Late) Pleistocene aridification.

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