Amino acid composition within a proteome is conventionally viewed as a property of individual protein function. However, specific nutrient scarcity has been shown to reshape which amino acids are encoded in the genome of microbes. Mosquitoes have fed on blood for 200 million years, relying on blood amino acids for reproduction. We wondered whether this ancient dependency has left an imprint on the mosquito proteome. Here we show a proteome-wide shift to lower isoleucine usage in blood-feeding mosquitoes, mirroring the known isoleucine deficiency of adult human hemoglobin. In comparing amino acid composition across the proteomes of blood-feeding and non-blood-feeding mosquitoes, we found that blood feeders show systematically lower isoleucine usage and that highly expressed gut enzymes that digest the blood meal are nearly isoleucine free. Analysis of 707 vertebrate genomes reveals that isoleucine deficiency in major hemoglobin subunits is shared among mammals. Specifically, all non-Malagasy primates, including humans, lack isoleucine in their adult hemoglobin subunits while retaining it in fetal and embryonic subunits. We find that two other major blood proteins, serum albumin and immunoglobulin G, also have reduced isoleucine levels (~1.4%) compared to the human proteome-wide average of 4.38%. Finally, we reasoned that this widespread isoleucine restriction could serve to defend adult red blood cells against isoleucine-dependent blood parasites that feed on them. We tested this hypothesis with the malaria parasite Plasmodium falciparum, which is known to arrest growth in adult red blood cells when extracellular isoleucine is withdrawn. We found that neonatal red blood cells purified from umbilical cord blood, which contain isoleucine-rich fetal hemoglobin, permit growth without extracellular isoleucine. This work demonstrates that nutritional scarcity is reflected in the genomes of animals, and that amino acid depletion of host protein sequences may serve a protective function against blood parasites.

Amino acid composition within a proteome is conventionally viewed as a property of individual protein function. However, specific nutrient scarcity has been shown to reshape which amino acids are enco...

The US Department of War has awarded Flagship Pioneering up to $47 million to build AI platforms that predict viral evolution before outbreaks happen. Here's what the ONTARGET deal means for biosecuri...

AI-predicted protein complex structures for over 2,800 viruses are now openly available in the AlphaFold Database . To better understand and protect against emerging pathogens, the dataset prioritises proteomes from viral families known to infect humans. This work was made possible thanks to an international collaboration between EMBL's European Bioinformatics Institute (EMBL-EBI), Google DeepMind, NVIDIA, Seoul National University, the University of Glasgow, the Swiss Institute of Bioinformatics (SIB), the Coalition for Epidemic Preparedness Innovations (CEPI), and Sungkyunkwan University (SKKU) in South Korea. This release also includes complexes computed independently of this collaboration by colleagues at Lund University in Sweden. Viruses rely on a complex network of specialised proteins which, among other things, allow them to interact with human cells. Visualising the 3D structure of these proteins can reveal the regions on a virus's surface that are key targets for diagnostics, therapeutics, and vaccines. Such information could help scientists respond more quickly in the event of a future pandemic. "Making these data open is critical for understanding viral diagnostics and developing treatments and vaccines," said Jo McEntyre, Interim Director of EMBL-EBI. "They can support faster and more effective responses to future pandemics. They also cover lesser-studied viruses and lower the barriers...

Amino acid composition within a proteome is conventionally viewed as a property of individual protein function. However, specific nutrient scarcity has been shown to reshape which amino acids are encoded in the genome of microbes. Mosquitoes have fed on blood for 200 million years, relying on blood amino acids for reproduction. We wondered whether this ancient dependency has left an imprint on the mosquito proteome. Here we show a proteome-wide shift to lower isoleucine usage in blood-feeding mosquitoes, mirroring the known isoleucine deficiency of adult human hemoglobin. In comparing amino acid composition across the proteomes of blood-feeding and non-blood-feeding mosquitoes, we found that blood feeders show systematically lower isoleucine usage and that highly expressed gut enzymes that digest the blood meal are nearly isoleucine free. Analysis of 707 vertebrate genomes reveals that isoleucine deficiency in major hemoglobin subunits is shared among mammals. Specifically, all non-Malagasy primates, including humans, lack isoleucine in their adult hemoglobin subunits while retaining it in fetal and embryonic subunits. We find that two other major blood proteins, serum albumin and immunoglobulin G, also have reduced isoleucine levels (~1.4%) compared to the human proteome-wide average of 4.38%. Finally, we reasoned that this widespread isoleucine restriction could serve to defend adult red blood cells against isoleucine-dependent blood parasites that feed on them. We tested this hypothesis with the malaria parasite Plasmodium falciparum, which is known to arrest growth in adult red blood cells when extracellular isoleucine is withdrawn. We found that neonatal red blood cells purified from umbilical cord blood, which contain isoleucine-rich fetal hemoglobin, permit growth without extracellular isoleucine. This work demonstrates that nutritional scarcity is reflected in the genomes of animals, and that amino acid depletion of host protein sequences may serve a protective function against blood parasites.

Neuroblastoma is a heterogeneous pediatric malignancy characterized by distinct genomic subgroups and cell-state plasticity between adrenergic (ADRN) and mesenchymal (MES) phenotypes. While small extracellular vesicles (sEVs) mediate pre-metastatic niche priming, the degree to which sEV proteomes reflect parental genomic and phenotypic identity remains unresolved. Here, we isolated sEVs from six neuroblastoma cell models (IMR-5/75, BE(2)-C, GI-ME-N, CLB-GA, LAN-6, and SK-N-FI) representing three genomic subgroups (MYCN-amplified, TERT-rearranged, and unaltered) using OptiPrep density gradient centrifugation followed by size exclusion chromatography and ultrafiltration. High-resolution mass spectrometry of sEV proteomes revealed that sEVs carry highly reproducible protein signatures that tightly correlate with the parental genomic subgroups. Analyzing paired cell/sEV samples, we demonstrate cell-to-EV concordance of lineage-specific markers: ADRN sEVs selectively enriched L1CAM and dopamine {beta}-hydroxylase (DBH), whereas MES sEVs enriched SERPINE1 and type III collagen (COL3A1). These findings indicate that neuroblastoma-derived sEVs systematically preserve both the genomic landscape and the lineage transdifferentiation states of their cells of origin. This study establishes a robust molecular foundation for utilizing sEV-based proteomics as a surrogate to track cellular plasticity and for studying sEV-mediated microenvironmental remodeling.

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Author summary Archaea are the least-studied of the three domains of life, yet they matter enormously: they flourish in extreme environments, drive global nutrient cycles, and are closely tied to the ...