| 1. |
- Nik-Zainal, Serena, et al.
(author)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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Journal article (peer-reviewed)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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| 2. |
- Enge, Swantje, et al.
(author)
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A supergene in seaweed flies modulates male traits and female perception
- 2023
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In: Proceedings of the Royal Society B: Biological Sciences. - 0962-8452 .- 1471-2954. ; 290:2008
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Journal article (peer-reviewed)abstract
- Supergenes, tightly linked sets of alleles, offer some of the most spectacular examples of polymorphism persisting under long-term balancing selection. However, we still do not understand their evolution and persistence, especially in the face of accumulation of deleterious elements. Here, we show that an overdominant supergene in seaweed flies, Coelopa frigida, modulates male traits, potentially facilitating disassortative mating and promoting intraspecific polymorphism. Across two continents, the Cf-Inv(1) supergene strongly affected the composition of male cuticular hydrocarbons (CHCs) but only weakly affected CHC composition in females. Using gas chromatography-electroantennographic detection, we show that females can sense male CHCs and that there may be differential perception between genotypes. Combining our phenotypic results with RNA-seq data, we show that candidate genes for CHC biosynthesis primarily show differential expression for Cf-Inv(1) in males but not females. Conversely, candidate genes for odorant detection were differentially expressed in both sexes but showed high levels of divergence between supergene haplotypes. We suggest that the reduced recombination between supergene haplotypes may have led to rapid divergence in mate preferences as well as increasing linkage between male traits, and overdominant loci. Together this probably helped to maintain the polymorphism despite deleterious effects in homozygotes.
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| 3. |
- Jahnke, Marlene, et al.
(author)
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Seascape genomics identify adaptive barriers correlated to tidal amplitude in the shore crab Carcinus maenas
- 2022
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In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 31:7, s. 1980-94
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Journal article (peer-reviewed)abstract
- Most marine invertebrates disperse during a planktonic larval stage that may drift for weeks with ocean currents. A challenge for larvae of coastal species is to return to coastal nursery habitats. Shore crab (Carcinus maenas L.) larvae are known to show tidal rhythmicity in vertical migration in tidal areas and circadian rhythmicity in micro-tidal areas, which seems to increase successful coastal settlement. We studied genome-wide differentiation based on 24,000 SNPs of 12 native populations of shore crab sampled from a large tidal amplitude gradient from macro-tidal (ca. 8 m) to micro-tidal (ca. 0.2 m). Dispersal and recruitment success of larvae was assessed with a Lagrangian biophysical model, which showed a strong effect of larval behavior on long-term connectivity, and dispersal barriers that partly coincided with different tidal environments. The genetic population structure showed a subdivision of the samples into three clusters, which represent micro-, meso- and macro-tidal areas. The genetic differentiation was mostly driven by 0.5% outlier loci, which showed strong allelic clines located at the limits between the three tidal areas. Demographic modelling suggested that the two genetic barriers have different origins. Differential gene expression of two clock genes (cyc and pdp1) further highlighted phenotypic differences among genetic clusters that are potentially linked to the differences in larval behaviour. Taken together, our seascape genomic study suggest that tidal regime acts as a strong selection force on shore crab population structure, consistent with larval behaviour affecting dispersal and recruitment success.
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