Armbruster, J. | bioRxiv Science

bioRxiv2024

Ancient climate changes and relaxed selection shape cave colonisation in North American cavefishes

Extreme environments serve as natural laboratories for studying evolutionary processes, with caves offering replicated instances of independent colonisations. The timing, mode, and genetic underpinnings underlying cave-obligate organismal evolution remains enigmatic. We integrate phylogenomics, fossils, paleoclimatic modeling, and newly sequenced genomes to elucidate the evolutionary history and adaptive processes of cave colonisation in the study group, the North American Amblyopsidae fishes. Amblyopsid fishes present a unique system for investigating cave evolution, encompassing surface, facultative cave-dwelling, and cave-obligate (troglomorphic) species. Using 1,105 exon markers and total-evidence dating, we reconstructed a robust phylogeny that supports the nested position of eyed, facultative cave-dwelling species within blind cavefishes. We identified three independent cave colonisations, dated to the Early Miocene (18.5 Mya), Late Miocene (10.0 Mya), and Pliocene (3.0 Mya). Evolutionary model testing supported a climate-relict hypothesis, suggesting that global cooling trends since the Early-Middle Eocene may have influenced cave colonisation. Comparative genomic analyses of 487 candidate genes revealed both relaxed and intensified selection on troglomorphy-related loci. We found more loci under relaxed selection, supporting neutral mutation as a significant mechanism in cave-obligate evolution. Our findings provide empirical support for climate-driven cave colonisation and offer insights into the complex interplay of selective pressures in extreme environments.

evolutionary biology↗

bioRxiv2022

Pro-apoptotic and anti-invasive properties underscore the tumor suppressing impact of myoglobin on subset of human breast cancer cells

Expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role, by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB, at normoxia, upregulated the expression of cell cyclins and increased cell survival while it prevented apoptosis in MCF7 cells. Also, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, loss of MB enhanced partial epithelial to mesenchymal transition, thus augmenting the migratory and invasive cell behavior. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy.

cancer biology↗