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Nature Papers on Gelada Genome, Modified Primer Editor for Plants, Variants Linked to Childlessness

By analyzing the genome of the gelada, an Old World monkey and close relative of the baboon that is found in highland areas of Ethiopia, a group led by scientists from Arizona State University have identified genetic signatures of high-altitude adaptation in the animals. In the study, which appears in this week's Nature Ecology & Evolution, the researchers sequenced and assembled the first gelada reference genome and combined it with detailed physiological, demographic, and morphological data collected from wild geladas. Through comparisons to other mammals, the researchers uncover a range of gelada-specific traits that may confer adaptation to their high-altitude environment, including evidence for increased lung capacity and positive selection in numerous hypoxia-related genes. Notably, gelada-specific amino acid substitutions in hemoglobin that were discovered did not alter oxygen-binding affinity, highlighting the need for functional assays to validate purely sequence-based finding. The work advances the current understanding of mechanisms of adaptation to extreme environments and "provides an avenue for research that may have a transformative impact on the study and treatment of hypoxia-related conditions," the researchers conclude.

A modified prime editor with improved editing efficacy in plants is described in this week's Nature Biotechnology. Despite the versatility of prime editors, their editing efficiency remains low and often variable between different target sites and cell types. To address this shortcoming, scientists from the Chinese Academy of Sciences engineered the protein component of prime editors and show that deleting the RT ribonuclease H domain and adding a viral nucleocapsid protein stimulate much higher prime editing efficiency in plants with no significant increase in byproducts or off-target editing. They demonstrate their approach by using the modified prime editor to generate rice with tolerance to two herbicides.

An analysis of hundreds of thousands of individuals of European descent appearing in Nature this week reveals that damaging mutations in selectively constrained genes are associated with a small but significantly increased likelihood of being childless. In the study, investigators from the Wellcome Sanger Institute looked at genomic and phenotypic data from more than 340,000 UK Biobank participants, aged between 39 and 73 years and deemed to be in the post-reproductive stage of life. They find a high burden of damaging variation in a group of roughly 3,000 loss-of-function-intolerant genes is associated with childlessness, primarily in males. The researchers note that although this genetic association accounts for less than 1 percent of the overall likelihood of being childless, especially when compared with more influential sociodemographic factors, it may influence how genes evolve over time. "We anticipate future studies that integrate genome-wide sequencing data on large population samples from a range of ancestries to more fully characterize the nature of selection pressures acting on damaging genetic variation in our species," the authors write.

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