Williams, W. | bioRxiv Science

bioRxiv2018

Genomic evidence for the degradation of terrestrial organic matter by pelagic Arctic Ocean Chloroflexi bacteria

The Arctic Ocean currently receives a large supply of global river discharge and terrestrial dissolved organic matter. Moreover, an increase in freshwater runoff and riverine transport of organic matter to the Arctic Ocean is a predicted consequence of thawing permafrost and increased precipitation. The fate of the terrestrial humic-rich organic material and its impact on the marine carbon cycle are largely unknown. Here, the first metagenomic survey of the Canada Basin in the Western Arctic Ocean showed that pelagic Chloroflexi from the Arctic Ocean are replete with aromatic compound degradation genes, acquired in part by lateral transfer from terrestrial bacteria. Our results imply marine Chloroflexi have the capacity to use terrestrial organic matter and that their role in the carbon cycle may increase with the changing hydrological cycle.

microbiology↗

bioRxiv2018

Functional Improbable Antibody Mutations Critical for HIV Broadly Neutralizing Antibody Development

HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID) catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, implying their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We outline a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs with key improbable mutations required for bnAb development. Our analysis suggests that through generations of viral escape, Env trimers evolved to hide in low probability regions of antibody sequence space.

immunology↗