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Science Papers Examine Baboon Gut Microbiomes, RNAi Role in Mammals

By studying the gut microbiomes of baboons, a team led by researchers from the University of Minnesota finds that most microbiome phenotypes in the animals are heritable to some degree, countering previous studies, including ones in humans, that indicate a limited role for genetics in the gut microbiome. In the study, which appears in this week's Science, the scientists analyzed 16,234 RNA sequencing-based microbiome profiles generated using fecal samples collected from 585 wild baboons over 14 years. They find that host genetic effects on the gut microbiome are nearly universal; controlling for diet, age, and socioecological variation, 97 percent of microbiome phenotypes were significantly heritable. Notably, they also find that a larger proportion of variation in microbiome data is attributable to environmental factors rather than host genetic factors, which aligns with studies conducted in other animals. Estimates of microbiome heritability also varied between dry and wet seasons, as well as with the baboons' diet and age. The scientists suggest that studies finding few heritable gut microbiome taxa in humans may have been limited because they were all cross-sectional and lacked data on environmental variables that can mask or modify heritability levels. "Future work will help to refine our understanding of these environmental influences, including whether they mediate and/or interact with the effects of host genotype," they write. Overall, the study argues that host genetics play a consistent and sometimes appreciable role in the microbial landscape and that microbiome traits are therefore visible to natural selection on the host genome, they conclude.

RNAi is known to be an antiviral defense mechanism employed by plants and invertebrates, with the protein Dicer targeting and cleaving double-stranded RNA produced during infection to create small interfering RNAs that degrade viral RNAs. Whether RNAi contributes to antiviral immunity in mammals, however, is controversial. In a paper appearing in Science this week, researchers from the Francis Crick Institute report the discovery of a Dicer isoform that is used by tissue stem cells to combat RNA viruses, including Zika virus and SARS-CoV-2, by cutting viral dsRNA to orchestrate antiviral RNAi. The finding "sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells," the authors write.

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