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Science Papers Present Variant With Role in Human Evolution, Male Mice Pass on Depression Susceptibility Via mRNA

An analysis of a gene that is shared by modern humans and their ancient Neanderthal and Denisovan relatives but with a protein-coding difference suggests that the variant may have had a role in human evolution. The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) is key to neural development and function, and altered NOVA1 splicing activity in humans is associated with neurological disorders. It also includes a single nucleotide substitution between the modern human genome and Neanderthal and Denisovan genomes. To better understand the functional importance of this amino acid change in humans, researchers from the University of California, San Diego, and collaborators used CRISPR-Cas9 genome editing to reintroduce the archaic allele into human pluripotent stem cells that could be followed via cortical organoids. As reported in this week's Science, the modification resulted in slower development and higher surface complexity, as well as synaptic changes, in the organoids. "Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution," the study's authors write. GenomeWeb has more on this, here.

A new study appearing in Science Advances reveals that male mice who develop depression-like symptoms can pass on depression susceptibility to their offspring via microRNAs in their sperm. While it is known that parental life experiences can affect the phenotypes of their offspring, such epigenetic inheritance is poorly understood, particularly for father-to-child transmission. In the study, a group led by investigators from Nanjing University induced depression in a mouse model by subjecting the animals to mild stressors for several weeks. While the offspring of these mice initially behaved identically to control mice, they developed depression-like symptoms more rapidly when exposed to stressors. The scientists identified an miRNA in the sperm of the depressed mice with a different expression profile than that of the control animals. Introducing the miRNA into mouse embryos resulted in neuronal differences and susceptibility to depression, while neutralization of the abnormal miRNAs reduced the animal's vulnerability to depression. The findings show that "depression-like phenotypes induced by paternal stress can be inherited by the offspring through a causal role of miRNAs in the sperm," the researchers write. "Understanding the epigenetic inheritance mechanism of depression offers a crucial dimension for the development of antidepressant treatments."

The Scan

Renewed Gain-of-Function Worries

The New York Times writes that the pandemic is renewing concerns about gain-of-function research.

Who's Getting the Patents?

A trio of researchers has analyzed gender trends in biomedical patents issued between 1976 and 2010 in the US, New Scientist reports.

Other Uses

CBS Sunday Morning looks at how mRNA vaccine technology could be applied beyond SARS-CoV-2.

PLOS Papers Present Analysis of Cervicovaginal Microbiome, Glycosylation in Model Archaea, More

In PLOS this week: functional potential of the cervicovaginal microbiome, glycosylation patterns in model archaea, and more.