Biology subjects

Hansen, M. M.

Publications and source records attributed to Hansen, M. M..

3 recordsLinked to original sources

bioRxiv2024

Leveraging whole genomes, mitochondrial DNA, and haploblocks to decipher complex demographic histories: an example from a broadly admixed arctic fish

The study of phylogeography has transitioned from mitochondrial haplotypes to genome-wide analyses, blurring the line between this field and population genomics. Whole-genome sequencing offers the opportunity to join use both and provides the density of markers necessary to investigate genetic linkage and recombination along the genome. This facilitates the unraveling of complex demographic histories of admixture between divergent lineages, as is often the case in species evolving in recently deglaciated habitats. In this study, we sequenced 1120 Arctic Char genomes from 33 populations across Canada and Western Greenland to characterize patterns of genetic variation and diversity, and how they are shaped by hybridization between the Arctic and Atlantic glacial lineages. Several lines of evidence supported mito-nuclear discordance in lineage distribution, with all Canadian populations under the 66th parallel being characterized by introgression from the Atlantic lineage, leading to higher nuclear genetic diversity. By scanning the genome using local PCAs, we identified putative low-recombining haploblocks as local ancestry tracts from either lineage and described the impacts of recombination on the introgression landscape in admixed populations. Finally, we inferred conflicting origins of recolonization using whole genomes vs. ancestry tracts for the Arctic lineage, suggesting that haplotypes sheltered from introgression by low recombination could enlighten complex post-glacial histories. Overall, we argue that Whole-Genome Sequencing, even at low depths of coverage, provides a versatile approach to the study of phylogeographic dynamics.

evolutionary biology↗

bioRxiv2024

Bridging species boundaries: eDNA and genetic analysis reveal hybrid settlement at the very end of American eel distribution

Documenting species distributions and hybridization patterns is paramount for elucidating biogeography and understanding speciation processes. Here we combined genetic specimen analysis and environmental DNA (eDNA) to investigate the presence of American eel (Anguilla rotrata) and American x European eel (Anguilla anguilla) hybrids in Greenland freshwater. We further tested the use of eDNA to document hybridization by using European eel mtDNA as a proxy for hybrid occurrence. Overall, eDNA analysis detected mainly American eel but also European eel mtDNA. This finding was validated by DNA sequencing, which identified 3 out of 26 captured eels (14.3%) carrying European eel mtDNA. Five eels (19.2%), including all three with European mtDNA, were heterozygous for species-specific nuclear gene variants, supporting a hybrid ancestry. Further, eDNA successfully identified eels in lakes where they were caught by fyke net fishing, extending their confirmed northern range by 40 km, and indicated eel presence >200km further north. The study provides an empirical demonstration of the use of eDNA to document hybrid occurrence and extends the reported northern distribution of eels in Greenland significantly beyond previous observations. Further, the existence of hybrid eels in Greenland may be key for understanding the complex mechanisms of hybridization between American and European eels.

genetics↗

bioRxiv2020

Phenotypic distribution of the stem-like melanoma initiating state depends on CDKN2A status

Human cancers can exhibit phenotype switching, resulting in cells that are more metastatic or that are more tolerant to treatment. However, the relationship between these aggressive states is not well understood. We investigated the dynamics of phenotypic switching in human melanoma cells by monitoring the fluorescent activity from a transgenic reporter of BRN2 promoter activation. Melanoma cells exhibit heterogeneous BRN2 expression patterns that are reestablished upon isolation and clonal outgrowth. Specifically, stable BRN2 expression was generally inherited over multiple generations while undergoing occasional bidirectional interconversion. We found that BRN2 low cells were required for tumor initiation and metastasis in animal engraftment assays but were more sensitive to targeted BRAF inhibition. In contrast, the BRN2 high state was not tumorigenic, but entry into this state was uniform and persistent among cells tolerant to targeted BRAF therapy. Single-cell RNA sequencing analyses revealed core programs exclusive to either the BRN2 high or low cells, each of which is present in ex vivo tumors, demonstrating the physiological relevance of these states. Our findings emphasize that one challenge of effectively targeting phenotype switching in melanoma as a therapeutic strategy could be balancing distinct aggressive phenotypes so that sensitizing tumors to BRAF inhibition does not inadvertently lead to further dissemination. TeaserUnraveling melanomas shape-shifting behavior: insights into how cancer cells swap between metastasis and drug evasion.

cancer biology↗