Biology subjects

Diuk-Wasser, M.

Publications and source records attributed to Diuk-Wasser, M..

2 recordsLinked to original sources

bioRxiv2020

The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

evolutionary biology↗

bioRxiv2020

Lactobacilli and other gastrointestinal microbiota of Peromyscus leucopus, reservoir host for agents of Lyme disease and other zoonoses in North America

The cricetine rodent Peromyscus leucopus is an important reservoir for several human zoonoses, including Lyme disease, in North America. Akin to hamsters, the white-footed deermouse has been unevenly characterized in comparison to the murid Mus musculus. To further understanding of P. leucopus total genomic content, we investigated gut microbiomes of an outbred colony of P. leucopus, inbred M. musculus, and a natural population of P. leucopus. Metagenome and whole genome sequencing were combined with microbiology and microscopy approaches. A focus was the genus Lactobacillus, four diverse species of which were isolated from forestomach and feces of colony P. leucopus. Three of the species--L. animalis, L. reuteri, and provisionally-named species "L. peromysci"--were identified in fecal metagenomes of wild P. leucopus but not discernibly in samples from M. musculus. L. johnsonii, the fourth species, was common in M. musculus but absent or sparse in wild P. leucopus. Also identified in both colony and natural populations were a Helicobacter sp. in feces but not stomach, and a Tritrichomonas sp. protozoan in cecum or feces. The gut metagenomes of colony P. leucopus were similar to those of colony M. musculus at the family or higher level and for major subsystems. But there were multiple differences between species and sexes within each species in their gut metagenomes at orthologous gene level. These findings provide a foundation for hypothesis-testing of functions of individual microbial species and for interventions, such as bait vaccines based on an autochthonous bacterium and targeting P. leucopus for transmission-blocking.

microbiology↗