scholarly journals The dynamics of adaptive genetic diversity during the early stages of clonal evolution

2018 ◽  
Vol 3 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Jamie R. Blundell ◽  
Katja Schwartz ◽  
Danielle Francois ◽  
Daniel S. Fisher ◽  
Gavin Sherlock ◽  
...  
2017 ◽  
Author(s):  
Jamie R. Blundell ◽  
Katja Schwartz ◽  
Danielle Francois ◽  
Daniel S. Fisher ◽  
Gavin Sherlock ◽  
...  

The dynamics of genetic diversity in large clonally-evolving cell populations are poorly understood, despite having implications for the treatment of cancer and microbial infections. Here, we combine barcode lineage tracking, sequencing of adaptive clones, and mathematical modelling of mutational dynamics to understand diversity changes during experimental evolution. We find that, despite differences in beneficial mutational mechanisms and fitness effects between two environments, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages. However, a crash in diversity follows, caused by highly-fit double-mutants fed from exponentially growing single-mutants, a process closely related to the classic Luria-Delbruck experiment. The diversity crash is likely to be a general feature of clonal evolution, however its timing and magnitude is stochastic and depends on the population size, the distribution of beneficial fitness effects, and patterns of epistasis.


2019 ◽  
Author(s):  
Christian Sailer ◽  
Jürg Stöcklin ◽  
Ueli Grossniklaus

AbstractApomixis, the asexual reproduction through seeds, is thought to provide reproductive assurance when ploidy is not even and/or when population density is low. Therefore, apomicts are expected to be more abundant, and the frequency of apomictic offspring higher, at early stages of primary succession when mates are rare.To test this hypothesis, we sampled facultative apomictic Hieracium pilosella L. along the successional gradient on a glacier forefield and determined their ploidy, the level of apomixis in their offspring, and the genetic diversity of the entire meta-population and within subpopulations.We found that apomixis is more common in odd- and aneuploid cytotypes, which are more frequent at early stages of primary succession. However, apomixis was uncommon at all successional stages and sexual hexaploids were dominating throughout. Reproductive assurance was reflected in the higher fertility of all odd-ploid apomictic plants (3x, 5x) by avoiding meiosis, illustrating that apomixis provides an escape from sterility, as proposed by Darlington. Odd-ploid plants are supposedly better colonizers (Baker’s law), which is supported by their higher occurrence close to the glacier snout. Independent of succession, we found gene flow between apomicts and sexuals, which allows for the continuous creation of new apomictic and sexual genotypes.We conclude that apomixis in H. pilosella does indeed provide an escape from sterility, and therefore reproductive assurance, in aneuploid cytotypes. We further propose that apomixis preserves beneficial combinations of unlinked alleles in every generation for as long as apomictic genotypes persist in the population.


2016 ◽  
Vol 26 (7) ◽  
pp. 2254-2266 ◽  
Author(s):  
Isabel Rodríguez-Quilón ◽  
Luis Santos-del-Blanco ◽  
María Jesús Serra-Varela ◽  
Jarkko Koskela ◽  
Santiago C. González-Martínez ◽  
...  

2016 ◽  
Vol 12 (3) ◽  
Author(s):  
Carl Vangestel ◽  
Alejandra Vázquez-Lobo ◽  
Pedro J. Martínez-García ◽  
Irina Calic ◽  
Jill L. Wegrzyn ◽  
...  

2017 ◽  
Author(s):  
Veronica Gonzalez-Pena ◽  
Matthew MacKay ◽  
Iwijn De Vlaminck ◽  
John Easton ◽  
Charles Gawad

AbstractEnsemble-averaged genome profiling of diagnostic samples suggests that acute leukemias harbor few somatic genetic alterations. We used single-cell exome and error-corrected sequencing to survey the genetic diversity underlyingETV6-RUNX1acute lymphoblastic leukemia (ALL) at high resolution. The survey uncovered a vast range of low-frequency genetic variants that were undetected in conventional bulk assays, including additional clone-specific “driver” RAS mutations. Single-cell exome sequencing revealed APOBEC mutagenesis to be important in disease initiation but not in progression and identified many more mutations per cell than previously found. Using this data, we created a branching model ofETV6-RUNX1ALL development that recapitulates the genetic features of patients. Exposure of leukemic populations to chemotherapy selected for specific clones in a dose-dependent manner. Together, these data have important implications for understanding the development and treatment response of childhood leukemia, and they provide a framework for using population genetics to deeply interrogate cancer clonal evolution.One-Sentence SummaryAPOBEC and replication-associated mutagenesis contribute to the development of ETV6-RUNX1 ALL, creating massive leukemic population genetic diversity that results in clonal differences in susceptibilities to chemotherapy.


PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0232282
Author(s):  
José G. Ham-Dueñas ◽  
Ricardo Canales-del-Castillo ◽  
Gary Voelker ◽  
Irene Ruvalcaba-Ortega ◽  
Carlos E. Aguirre-Calderón ◽  
...  

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