Polyploidy, the result of whole-genome duplication (WGD), is a major driver of eukaryote evolution. Yet WGDs are hugely disruptive mutations, and we still lack a clear understanding of their fitness consequences. Here, we study whether WGDs result in greater diversity of genomic structural variants (SVs) and how they influence evolutionary dynamics in a plant genus, Cochlearia (Brassicaceae). By using long-read sequencing and a graph-based pangenome, we find both negative and positive interactions between WGDs and SVs. Masking of recessive mutations due to WGDs leads to a progressive accumulation of deleterious SVs across four ploidal levels (from diploids to octoploids), likely reducing the adaptive potential of polyploid populations. However, we also discover putative benefits arising from SV accumulation, as more ploidy-specific SVs harbor signals of local adaptation in polyploids than in diploids. Together, our results suggest that SVs play diverse and contrasting roles in the evolutionary trajectories of young polyploids.
Understanding the genetic basis of reproductive isolation is a central issue in the study of speciation. Structural variants (SVs); that is, structural changes in DNA, including inversions, translocations, insertions, deletions, and duplications, are common in a broad range of organisms and have been hypothesized to play a central role in speciation. Recent advances in molecular and statistical methods have identified structural variants, especially inversions, underlying ecologically important traits; thus, suggesting these mutations contribute to adaptation. However, the contribution of structural variants to reproductive isolation between species-and the underlying mechanism by which structural variants most often contribute to speciation-remain unclear. Here, we review (i) different mechanisms by which structural variants can generate or maintain reproductive isolation; (ii) patterns expected with these different mechanisms; and (iii) relevant empirical examples of each. We also summarize the available sequencing and bioinformatic methods to detect structural variants. Lastly, we suggest empirical approaches and new research directions to help obtain a more complete assessment of the role of structural variants in speciation.
- Klíčová slova
- hybridization, reproductive isolation, suppressed recombination,
- MeSH
- biologická evoluce MeSH
- druhová specificita * MeSH
- fenotyp MeSH
- fyziologická adaptace MeSH
- lidé MeSH
- molekulární evoluce MeSH
- reprodukční izolace MeSH
- strukturální variace genomu genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
- MeSH
- dítě MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- lidé MeSH
- lidské chromozomy, pár 9 genetika MeSH
- meduloblastom klasifikace genetika patologie MeSH
- myši MeSH
- onkogeny genetika MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- strukturální variace genomu genetika MeSH
- transkripční faktory genetika metabolismus MeSH
- zesilovače transkripce genetika MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- GFI1 protein, human MeSH Prohlížeč
- GFI1B protein, human MeSH Prohlížeč
- protoonkogenní proteiny MeSH
- represorové proteiny MeSH
- transkripční faktory MeSH
