Plausible Emergence and Self Assembly of a Primitive Phospholipid from Reduced Phosphorus on the Primordial Earth.

How life arose on the primitive Earth is one of the biggest questions in science. Biomolecular emergence scenarios have proliferated in the literature but accounting for the ubiquity of oxidized (+ 5) phosphate (PO43-) in extant biochemistries has been challenging due to the dearth of phosphate and molecular oxygen on the primordial Earth. A compelling body of work suggests that exogenous schreibersite ((Fe,Ni)3P) was delivered to Earth via meteorite impacts during the Heavy Bombardment (ca. 4.1-3.8 Gya) and there converted to reduced P oxyanions (e.g., phosphite (HPO32-) and hypophosphite (H2PO2-)) and phosphonates. Inspired by this idea, we review the relevant literature to deduce a plausible reduced phospholipid analog of modern phosphatidylcholines that could have emerged in a primordial hydrothermal setting. A shallow alkaline lacustrine basin underlain by active hydrothermal fissures and meteoritic schreibersite-, clay-, and metal-enriched sediments is envisioned. The water column is laden with known and putative primordial hydrothermal reagents. Small system dimensions and thermal- and UV-driven evaporation further concentrate chemical precursors. We hypothesize that a reduced phospholipid arises from Fischer-Tropsch-type (FTT) production of a C8 alkanoic acid, which condenses with an organophosphinate (derived from schreibersite corrosion to hypophosphite with subsequent methylation/oxidation), to yield a reduced protophospholipid. This then condenses with an α-amino nitrile (derived from Strecker-type reactions) to form the polar head. Preliminary modeling results indicate that reduced phospholipids do not aggregate rapidly; however, single layer micelles are stable up to aggregates with approximately 100 molecules.

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.