Spd-2 gene duplication reveals cell-type-specific pericentriolar material regulation.

Centrosomes are multi-protein organelles that function as microtubule (MT) organizing centers (MTOCs), ensuring spindle formation and chromosome segregation during cell division.1,2,3 Centrosome structure includes core centrioles that recruit pericentriolar material (PCM) that anchors γ-tubulin to nucleate MTs.1,2 In Drosophila melanogaster, PCM organization depends on proper regulation of proteins like Spd-2, which dynamically localizes to centrosomes and is required for PCM, γ-tubulin, and MTOC activity in brain neuroblast (NB) mitosis and male spermatocyte (SC) meiosis.4,5,6,7,8 Some cells have distinct requirements for MTOC activity due to differences in characteristics like cell size9,10 or whether they are mitotic or meiotic.11,12 How centrosome proteins achieve cell-type-specific functional differences is poorly understood. Previous work identified alternative splicing13 and binding partners14 as contributors to cell-type-specific differences in centrosome function. Gene duplication, which can generate paralogs with specialized functions,15,16 is also implicated in centrosome gene evolution,17 including cell-type-specific centrosome genes.18,19 To gain insight into cell-type-specific differences in centrosome protein function and regulation, we investigated a duplication of Spd-2 in Drosophila willistoni, which has Spd-2A (ancestral) and Spd-2B (derived). We find that Spd-2A functions in NB mitosis, whereas Spd-2B functions in SC meiosis. Ectopically expressed Spd-2B accumulates and functions in mitotic NBs, but ectopically expressed Spd-2A failed to accumulate in meiotic SCs, suggesting cell-type-specific differences in translation or protein stability. We mapped this failure to accumulate and function in meiosis to the C-terminal tail domain of Spd-2A, revealing a novel regulatory mechanism that can potentially achieve differences in PCM function across cell types.

Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin.

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population, and how this heterogeneity affects virus evolution. Here we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of the A/Hong Kong/45/2019 (H3N2) and A/Perth/16/2009 (H3N2) strains affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that fixed in influenza variants after 2020 cause the greatest escape from sera from younger individuals. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups, and suggest approaches to understand how this heterogeneous selection shapes viral evolution.

Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution.

Munoz-Alia and colleagues1 demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.

Ancient Coretention of Paralogs of Cid Centromeric Histones and Cal1 Chaperones in Mosquito Species.

Despite their essential role in chromosome segregation in most eukaryotes, centromeric histones (CenH3s) evolve rapidly and are subject to gene turnover. We previously identified four instances of gene duplication and specialization of Cid, which encodes for the CenH3 in Drosophila. We hypothesized that retention of specialized Cid paralogs could be selectively advantageous to resolve the intralocus conflict that occurs on essential genes like Cid, which are subject to divergent selective pressures to perform multiple functions. We proposed that intralocus conflict could be a widespread phenomenon that drives evolutionary innovation in centromeric proteins. If this were the case, we might expect to find other instances of coretention and specialization of centromeric proteins during animal evolution. Consistent with this hypothesis, we find that most mosquito species encode two CenH3 (mosqCid) genes, mosqCid1 and mosqCid2, which have been coretained for over 150 My. In addition, Aedes species encode a third mosqCid3 gene, which arose from an independent gene duplication of mosqCid1. Like Drosophila Cid paralogs, mosqCid paralogs evolve under different selective constraints and show tissue-specific expression patterns. Analysis of mosqCid N-terminal protein motifs further supports the model that mosqCid paralogs have functionally diverged. Extending our survey to other centromeric proteins, we find that all Anopheles mosquitoes encode two CAL1 paralogs, which are the chaperones that deposit CenH3 proteins at centromeres in Diptera, but a single CENP-C paralog. The ancient coretention of paralogs of centromeric proteins adds further support to the hypothesis that intralocus conflict can drive their coretention and functional specialization.