The conditions that led to the formation of the first organisms and the ways that life originates from a lifeless chemical soup are poorly understood. The recent hypothesis of “RNA-peptide coevolution” suggests that the current close relationship between amino acids and nucleobases may well have extended to the origin of life. We now show how the interplay between these compound classes can give rise to new self-replicating molecules using a dynamic combinatorial approach. We report two strategies for the fabrication of chimeric amino acid/nucleobase self-replicating macrocycles capable of exponential growth. The first one relies on mixing nucleobase- and peptide-based building blocks, where the ligation of these two gives rise to highly specific chimeric ring structures. The second one starts from peptide nucleic acid (PNA) building blocks in which nucleobases are already linked to amino acids from the start. While previously reported nucleic acid-based self-replicating systems rely on presynthesis of (short) oligonucleotide sequences, self-replication in the present systems start from units containing only a single nucleobase. Self-replication is accompanied by self-assembly, spontaneously giving rise to an ordered one-dimensional arrangement of nucleobase nanostructures.

The ability of molecules and systems to make copies of themselves and the ability of molecules to fold into stable, well-defined three-dimensional conformations are of considerable importance in the formation and persistence of life. The question of how, during the emergence of life, oligomerization reactions become selective and channel these reactions toward a small number of specific products remains largely unanswered. Herein, we demonstrate a fully synthetic chemical system where structurally complex foldamers and self-replicating assemblies emerge spontaneously and with high selectivity from pools of oligomers as a result of forming noncovalent interactions. Whether foldamers or replicators form depends on remarkably small differences in building block structures and composition and experimental conditions. We also observed the dynamic transformation of a foldamer into a replicator. These results show that the structural requirements/design criteria for building blocks that lead to foldamers are similar to those that lead to replicators. What determines whether folding or replication takes place is not necessarily the type of noncovalent interaction, but only whether they occur intra- or intermolecularly. This work brings together, for the first time, the fields of replicator and foldamer chemistry.

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present.

The russet mite, Aceria anthocoptes (Nalepa), is the only eriophyoid that has been recorded on Cirsium arvense (L.) Scop. It has been noted in several European countries and recently in the USA. In this study we explored the geographic and host-related variability of Aceria spp. inhabiting different Cirsium spp. We applied landmark-based geometric morphometric methods to study morphological variability of three body regions (ventral, coxigenital and prodorsal) of 13 Aceria spp. populations inhabiting five Cirsium spp. in Serbia (Europe) and four Cirsium spp. in Colorado (North America). Analyses of size and shape variation revealed statistically significant differences between Aceria spp. living on European native and North American native Cirsium spp., as well as between A. anthocoptes s.s. inhabiting European C. arvense and North American C. arvense. The coxigenital region was the most informative when considering inter-population shape differences. European Aceria spp. dwelling on Cirsium spp., including A. anthocoptes s.s. from C. arvense, are characterized by higher inter-population size and shape variability than their North American counterparts. This finding supports a Eurasian origin of A. anthocoptes, presumed to consist of a complex of cryptic taxa probably coevolved with host plants in the native environment. Morphological similarity among Aceria spp. inhabiting North American native Cirsium spp. may indicate that speciation of A. anthocoptes started relatively soon after the host shift to plants different from C. arvense in the invaded region.

Dynamic covalent chemistry (DCC) has proven to be a valuable tool in creating fascinating molecules, structures, and emergent properties in fully synthetic systems. Here we report a system that uses two dynamic covalent bonds in tandem, namely disulfides and hydrazones, for the formation of hydrogels containing biologically relevant ligands. The reversibility of disulfide bonds allows fiber formation upon oxidation of dithiol‐peptide building block, while the reaction between NH−NH2 functionalized C‐terminus and aldehyde cross‐linkers results in a gel. The same bond‐forming reaction was exploited for the “decoration” of the supramolecular assemblies by cell‐adhesion‐promoting sequences (RGD and LDV). Fast triggered gelation, cytocompatibility and ability to “on‐demand” chemically customize fibrillar scaffold offer potential for applying these systems as a bioactive platform for cell culture and tissue engineering.