Choi, J.-P. | Search bioRxiv

bioRxiv2024

Dokdo sea lion Zalophus japonicus genome reveals its evolutionary trajectory before extinction

BackgroundThe Dokdo sea lion (Zalophus japonicus), commonly referred to as Gangchi in Korea and known as the Japanese sea lion, was endemic to the Northwest Pacific coast before becoming extinct in the 1950s. Little is known about its origins, speciation compared to other Otariidae species or how the rapid decline affected the species genetic diversity. ResultsTo raise the Dokdo sea lion from this relative obscurity, we sequenced DNA from 16 Z. japonicus bone fragments, obtained from Dokdo and Ulleungdo islands in Korea. Our analysis establishes Z. japonicus as the earliest diverged species within its genus, significantly redefining its evolutionary relationship with the California (Z. californianus) and Galapagos (Z. wollebaeki) sea lions. This genome-scale analysis clarifies the phylogeny of Z. japonicus, shedding light on its speciation and the evolutionary pathways that shaped its genetic diversity before its extinction. In addition, we discovered, population decline of the Z. japonicus started already 1,000 years ago, however, Z. japonicus genome maintained a relatively high heterozygosity despite, nearing extinction. ConclusionsOur genome-scale analysis eliminated ambiguity in Z. japonicus phylogeny, and shed light on the evolutionary pathways underlying its speciation. This study highlights the importance of the genome-scale analysis for extinct species to understand their complex evolutionary histories and conservation status.

genomics↗

bioRxiv2023

De novo fatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness

AbstractInvariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in iNKT cells is very limited. It is also not clear whether such metabolic regulation of iNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediated de novo fatty-acid synthesis is required for the survival of iNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung iNKT cells from WT mice that were developing asthma. Cd4-CreAcc1fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, iNKT cell-deficient mice that were reconstituted with ACC1-deficient iNKT cells failed to develop asthma, unlike when WT iNKT cells were transferred. ACC1 deficiency in iNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR){gamma}, but increased glycolytic capacity that promoted iNKT-cell death. Furthermore, circulating iNKT cells from allergic-asthma patients expressed higher ACC1 and PPARG levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus, de novo fatty-acid synthesis prevents iNKT-cell death via an ACC1-FABP-PPAR{gamma} axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.

immunology↗