Volume 228, Issue 3, November 2024

In this review, Watteyne et al. focus on functional insights on neuropeptide signaling gained from comprehensive mapping of the neuropeptide signaling network and behavioral studies in the nematode Caenorhabditis elegans. The authors summarize recent discoveries on the evolutionary conservation of neuropeptide systems, the structure of the peptide signaling network, as well as functional knowledge and peptidergic circuit motifs emerging for behavioral studies in C. elegans.

A gross chromosomal rearrangement (GCR) is an abnormal structural change of a native chromosome. Examples of GCRs include deletions, duplications, inversions, and translocations. GCRs can lead to genetic diseases such as cancer. A previous study implicated the spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during cell division, in facilitating the formation of GCRs. In this study, Yao et al. show that this is not the case; the SAC does not promote GCR.

Variants in cytochrome P450s (CYPs) can alter metabolism, causing dosing issues and adverse reactions. Moreover, it is unclear why nearly identical CYP homologs have distinct properties. Boyle et al. used mutational scanning to measure the protein abundance of 7,660 CYP2C19 variants in human cells. Joint analysis of CYP2C19 and CYP2C9 scans showed differing abundances in substrate recognition sites. Abundances of amino acid swaps between the homologs indicated differing thermodynamic stability properties. The authors also annotated 368 CYP2C19 variants in the gnomAD database, finding that 43% had decreased abundance. This study provides foundational insight into the structure and function of these versatile enzymes.

In this study, Lyulina et al. analyze a new class of linkage disequilibrium metrics that quantify the homoplasy produced by recombination. The authors introduce a mathematical framework for predicting how these homoplasy measures depend on the rates of recombination and recurrent mutation, the strength of negative selection and genetic drift, and the present-day frequencies of the mutant alleles. These results expand our toolbox for understanding the patterns of genetic linkage in large genomic datasets.