Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models—the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.

In the fight against antimicrobial resistance, bacteriophages are a promising alternative to antibiotics. However, due to their narrow spectra, phage therapy requires the careful matching between the host and bacteriophage to be effective. Despite our best efforts, nature remains as the only source of novel phage specificity. Directed evolution can potentially open an avenue for engineering phage specificity and improving qualities of phages that are not strongly selected for in their natural environments but are important for therapeutic applications. In this work, we present a strategy that generates large libraries of replication-competent phage variants directly from synthetic DNA fragments, with no restriction on their host specificity. Using the T7 bacteriophage as a proof-of-concept, we created a large library of tail fiber mutants with at least 107 unique variants. From this library, we identified mutants that have broadened specificity as evidenced by their novel lytic activity against Yersinia enterocolitica, a strain that the wildtype T7 was unable to lyse. Using the same concept, mutants with improved lytic efficiency and characteristics, such as lytic condition tolerance and resistance suppression, were also identified. However, the observed limitations in altering host specificity by tail fiber mutagenesis suggest that other bottlenecks could be of equal or even greater importance.

Ehrlichia canis (Rickettsiales; Anaplasmataceae) is one of the most prevalent tick-borne pathogens of dogs globally. The bacterium infects monocytes and is the aetiological agent of canine monocytic ehrlichiosis. For many decades Australia was thought to be free of the pathogen, but this abruptly changed in May 2020 when E. canis was detected in several dogs from Kununurra, Western Australia. Subsequent surveillance activities found unexpectedly large scale spread of E. canis throughout much of northern Australia. To gain insight into the genetic relationships of the Australian strain and its potential origin, we undertook a genomic analysis of E. canis positive domestic dog and tick (Rhipicephalus linnaei) samples from the north of Western Australia, the far north of South Australia and the Northern Territory, covering thousands of square kilometres. We obtained complete E. canis genomes from each of the three states, plus an additional 16 partial genomes, substantially increasing publicly available E. canis genetic resources. The Australian E. canis genomes were highly conserved across large geographic distances. Outside of Australia, the genomes were most similar to E. canis YZ-1 from China, although few reference sequences were available. We analysed the variable trp36 gene to obtain greater phylogenetic signal, which demonstrated that the Australian E. canis belonged to the Taiwan genotype, comprised of samples from Taiwan, China, Thailand and Turkey. Taken together, our findings suggest that E. canis in Australia may have originated from Asia or the Middle East and spread throughout northern and central Australia following its introduction.

Rates of species formation vary widely across the tree of life and contribute to massive disparities in species richness among clades. This variation can emerge from differences in metapopulation-level processes that affect the rates at which lineages diverge, persist, and evolve reproductive barriers and ecological differentiation. For example, populations that evolve reproductive barriers quickly should form new species at faster rates than populations that acquire reproductive barriers more slowly. This expectation implicitly links microevolutionary processes (the evolution of populations) and macroevolutionary patterns (the profound disparity in speciation rate across taxa). Here, leveraging extensive field sampling from the Neotropical Cerrado biome in a biogeographically controlled natural experiment, we test the role of an important microevolutionary process—the propensity for population isolation—as a control on speciation rate in lizards and snakes. By quantifying population genomic structure across a set of codistributed taxa with extensive and phylogenetically independent variation in speciation rate, we show that broad-scale patterns of species formation are decoupled from demographic and genetic processes that promote the formation of population isolates. Population isolation is likely a critical stage of speciation for many taxa, but our results suggest that interspecific variability in the propensity for isolation has little influence on speciation rates. These results suggest that other stages of speciation—including the rate at which reproductive barriers evolve and the extent to which newly formed populations persist—are likely to play a larger role than population isolation in controlling speciation rate variation in squamates.

This study describes an optimized DNA extraction protocol targeting ultrashort DNA molecules from single rootless hairs. It was applied to the oldest samples available to us: locks of hairs that were found in relics associated with the Romanov family. Published mitochondrial DNA genome sequences of Tsar Nicholas II and his wife, Tsarina Alexandra, made these samples ideal to assess this DNA extraction protocol and evaluate the types of genetic information that can be recovered by sequencing ultrashort fragments. Using this method, the mtGenome of the Tsarina’s lineage was identified in hairs that were concealed in a pendant made by Karl Fabergé for Alexandra Feodorovna Romanov. In addition, to determine if the lock originated from more than one individual, two hairs from the locket were extracted independently and converted into Illumina libraries for shotgun sequencing on a NextSeq 500 platform. From these data, autosomal SNPs were analyzed to assess relatedness. The results indicated that the two hairs came from a single individual. Genetic testing of hairs that were found in the second artifact, a framed photograph of Louise of Hesse-Kassel, Queen of Denmark and maternal grandmother of Tsar Nicholas II, revealed that the hair belonged to a woman who shared Tsar Nicholas’ maternal lineage, including the well-known point heteroplasmy at position 16169.