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- Tobler, Michael, et al.
(author)
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Convergent changes in the trophic ecology of extremophile fish occurring along replicated environmental gradients
- 2015
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In: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 60:4, s. 768-780
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Journal article (peer-reviewed)abstract
- Divergent selection along environmental gradients connecting locally restricted extreme habitats and adjacent benign habitats can shape convergent evolution of traits involved in coping with physiochemical stressors and can drive speciation. At the same time, the presence of such stressors alters aspects of the biotic environment, including resource availability and competitive regimes. However, it remains unclear whether and how the ecology of populations occurring in both extreme and benign environments varies in a predictable fashion. We investigated the trophic ecology of live-bearing fishes of the genus Poecilia that have independently colonised multiple springs containing toxic hydrogen sulphide in southern Mexico. Sulphide spring fish are adapted to the unique environmental conditions and are reproductively isolated from ancestral populations in adjacent non-sulphidic habitats. We used gut content analyses to test whether colonisation of extreme habitats was accompanied by shifts of trophic resource use and expansions of trophic niche width. Furthermore, we tested whether dietary shifts were reflected in trophic morphology by comparing intestinal tract lengths among populations using both wild-caught and common garden-raised individuals. Gut content analyses revealed that fish inhabiting toxic springs expanded their trophic niche width and changed their dietary resource use from detritus and algae to sulphide bacteria and invertebrates. This dietary shift was paralleled by changes in intestinal tract morphology, whereby sulphide spring fish had shorter intestines than fish from adjacent non-sulphidic habitats. Analysis of common garden-raised fish indicated that morphological differences between sulphidic and non-sulphidic populations are at least in part due to genetic differentiation. Both patterns of trophic resource use and differentiation in trophic morphology were consistent across replicated pairs of sulphidic and non-sulphidic populations, although the magnitude of differentiation varied among river drainages. Our results suggest that colonisation of and adaptation to sulphide springs in southern Mexico was paralleled by convergent changes in trophic ecology. This highlights the complexity of environmental gradients and the necessity of considering multiple sources of selection when studying the evolution of complex phenotypes.
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- Zivanovic, Andrej, et al.
(author)
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Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer
- 2023
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In: NAR Cancer. - : Oxford University Press. - 2632-8674. ; 5:3
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Journal article (peer-reviewed)abstract
- Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.
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