Liam M. Longo

Polyphosphate kinase 2 (PPK2) enzymes catalyze phosphoryl transfer from polyphosphate to nucleotides and are divided into three classes, each presumed to have different catalytic preferences. With relevance to biotechnology, medicine, and primitive biology, there is significant interest in understanding the evolutionary history of PPK2 enzymes and predicting their functional properties. We reasoned that the distribution and pairing preferences of PPK2 gene classes across the prokaryote tree of life may shed light on these questions. PPK2 was found to be a dynamic gene family, often present in only a subset of species within a clade, even when considering a single genus. Although all possible PPK2 pairs were observed, a ~2-fold enrichment for Class I enzymes in species with multiple PPK2 genes strongly shapes pairing preferences. PPK2 class preference in the absence of PPK1, which synthesizes rather than utilizes polyphosphate, indicates the potential for functional adaptation and/or promiscuity with respect to reaction directionality for all classes, a feature that has previously been associated only with Class I. Patterns of adjacent PPK2 genes revealed signatures of gene duplication, as adjacent genes overwhelmingly belonged to the same class, as well as the potential for an added layer of PPK2 dynamics: hetero-oligomerization of single-domain Class II enzymes to recapitulate the structure of two-domain Class II enzymes. Finally, an updated PPK2 tree constructed from domains instead of genes calls into question established narratives of PPK2 evolution, putting new limits on the extent to which nucleobase promiscuity can be invoked in the early evolution of this family.

In 1966, Margaret Dayhoff reasoned that duplication and fusion is a fundamental mechanism for generating protein complexity. Her insight inspired generations of scientists, several of whom would demonstrate this trajectory with short peptides that symmetrically assemble into a contemporary protein architecture. But how did these oligomerizing peptides, able to adopt complex conformations, emerge in the first place? In the present review, the evolution of an ancient and ubiquitous nucleic acid-binding element is traced from a simple, heterochiral peptide that coacervates with RNA to a folded-domain that binds with high affinity to the minor groove of double-stranded DNA.

An unresolved question in the origin and evolution of life is whether a continuous path from geochemical precursors to the majority of molecules in the biosphere can be reconstructed from modern-day biochemistry. Here we identified a feasible path by simulating the evolution of biosphere-scale metabolism, using only known biochemical reactions and models of primitive coenzymes. We find that purine synthesis constitutes a bottleneck for metabolic expansion, which can be alleviated by non-autocatalytic phosphoryl coupling agents. Early phases of the expansion are enriched with enzymes that are metal dependent and structurally symmetric, supporting models of early biochemical evolution. This expansion trajectory suggests distinct hypotheses regarding the tempo, mode and timing of metabolic pathway evolution, including a late appearance of methane metabolisms and oxygenic photosynthesis consistent with the geochemical record. The concordance between biological and geological analyses suggests that this trajectory provides a plausible evolutionary history for the vast majority of core biochemistry

Understanding the emergence and evolution of agency is one of the great challenges in both biological research and philosophy. Hiroki Kojima (University of Tokyo), Eran Agmon (University of Connecticut), and I will bring agential studies into the laboratory by constructing a real-time evolution platform in which populations of organic (B-life) and digital (A-life) organisms are under mutual control and poised to form mutualistic community structures. Will community structure promote the emergence of agential features in the A-life population? Stay tuned! Calls for two open positions in Tokyo (Longo Lab) and one open position in Connecticut (Agmon Lab with support mentorship from Co-I Kojima) will follow shortly.

After a brief stint at her home institution in Stockholm, Marina has returned to the Longo Lab to continue her research on the evolution of exon structure (and provide some much needed programming mentorship to all those around her). Welcome back, Marina!

Prof. Gruić Sovulj is an expert in the enzymology of amino-acyl tRNA synthetases, the enzymes that define the genetic code. During her 2-month visit to the Longo Lab at ELSI, she will use bioinformatic approaches to study the evolution of this most important enzyme class.

Tatsuya received a Bachelor's degree in Biological Chemistry from the University of Toronto. As a student in the ELSI Graduate Program, his research efforts will focus on the origin of life and the emergence of complex biopolymer structure. Welcome, Tatsuya!