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Hernandez, C. E.

Publications and source records attributed to Hernandez, C. E..

2 recordsLinked to original sources

Global drivers of diversification in a marine species complex

Investigating historical gene flow in species complexes can indicate how environmental and reproductive barriers shape genome divergence before speciation. The processes influencing species diversification under environmental change remain one of the central focal points of evolutionary biology, particularly for marine organisms with high dispersal potential. We investigated genome-wide divergence, introgression patterns and inferred demographic history between species pairs of all extant rock lobster species (Jasus spp.), a complex with long larval duration, that has populated continental shelf and seamount habitats around the globe at approximately 40{degrees}S. Genetic differentiation patterns revealed the effects of the environment and geographic isolation. Species associated with the same habitat structure (either continental shelf or seamount/island) shared a common ancestry, even though the habitats were not adjacent. Differences in benthic temperature explained a significant proportion (41.3%) of the genetic differentiation. The Eastern Pacific species pair of J. caveorum and J. frontalis retained a signal of strict isolation following ancient migration, whereas species pairs from Australia and Africa and seamounts in the Indian and Atlantic oceans included events of introgression after secondary contact. Parameters estimated for time in isolation and gene flow were congruent with genetic differentiation metrics suggesting that the observed differentiation patterns are the product of migration and genetic drift. Our results reveal important effects of habitat and demographic processes on the divergence of species within the genus Jasus providing the first empirical study of genome-wide drivers of diversification that incorporates all extant species in a marine genus with long pelagic larval duration.

evolutionary biology

ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell survival

Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, and new molecular insights are necessary for prognostic and therapeutic advances. Here we demonstrate in orthotopic mouse models that dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its N-terminally truncated splice variant t-DARPP promote SCLC growth through increased proliferation, Akt/Erk-mediated survival and anti-apoptotic signaling. DARPP-32 and t-DARPP proteins are overexpressed in SCLC patient-derived tumor tissue, but virtually undetectable in physiologically normal lung. RNA sequencing analysis reveals a subset of SCLC patients with high tumoral t-DARPP expression and upregulated Notch signaling genes, including achaete-scute homologue 1 (ASCL1). We show that DARPP-32 isoforms are transcriptionally activated by ASCL1 in human SCLC cells. Taken together, we demonstrate new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.

cancer biology