The origin and structural evolution of de novo genes in Drosophila

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 27, 2024

Abstract Recent studies reveal that de novo gene origination from previously non-genic sequences is a common mechanism for innovation. These young genes provide an opportunity to study the structural and functional origins of proteins. Here, we combine high-quality base-level whole-genome alignments computational modeling origination, evolution, protein structures lineage-specific genes. We identify 555 candidates in D. melanogaster originated within Drosophilinae lineage. Sequence composition, evolutionary rates, expression patterns indicate possible gradual or adaptive shifts with their ages. Surprisingly, find little overall changes several potentially well-folded structures. Ancestral sequence reconstruction analysis reveals most are often born well-folded. Single-cell RNA-seq testis shows although enriched spermatocytes, biased towards early spermatogenesis stage, indicating important but less emphasized roles germline cells testis. This provides systematic overview origin, -specific

Язык: Английский

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The hidden bacterial microproteome

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Integrating AlphaFold pLDDT Scores into CABS-flex for Enhanced Protein Flexibility Simulations

Computational and Structural Biotechnology Journal, Год журнала: 2024, Номер 23, С. 4350 - 4356

Опубликована: Ноя. 30, 2024

Язык: Английский

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The Rapid Evolution of De Novo Proteins in Structure and Complex

Genome Biology and Evolution, Год журнала: 2024, Номер 16(6)

Опубликована: Май 16, 2024

Abstract Recent studies in the rice genome-wide have established that de novo genes, evolving from noncoding sequences, enhance protein diversity through a stepwise process. However, pattern and rate of their evolution structure over time remain unclear. Here, we addressed these issues within surprisingly short evolutionary timescale (<1 million years for 97% Oryza genes) with comparative approaches to gene duplicates. We found genes evolve faster than duplicates intrinsically disordered regions (such as random coils), secondary elements α helix β strand), hydrophobicity, molecular recognition features. In proteins, specifically, observed an 8% 14% decay coils region lengths 2.3% 6.5% increase structured elements, features, per on average. These patterns structural align changes amino acid composition well. also revealed higher positive charges but smaller weights proteins Tertiary predictions showed most though not typically well folded own, readily form low-energy compact complexes other facilitated by extensive residue contacts conformational flexibility, suggesting faster-binding scenario promote interaction. analyses illuminate rapid genomes, originating highlighting quick transformation into active, complex-forming components remarkably timeframe.

Язык: Английский

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The Cryptic Bacterial Microproteome

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 18, 2024

Microproteins encoded by small open reading frames (smORFs) comprise the "dark matter" of proteomes. Although functional microproteins were identified in diverse organisms from all three domains life, bacterial smORFs remain poorly characterized. In this comprehensive study intergenic (ismORFs, 15-70 codons) 5,668 genomes family Enterobacteriaceae, we 67,297 clusters ismORFs subject to purifying selection. The mainly code for hydrophobic, potentially transmembrane, unstructured, or minimally structured microproteins. Using AlphaFold Multimer, predicted interactions some transcribed with proteins neighboring genes, revealing potential regulate activity various proteins, particularly, under stress. We compiled a catalog microprotein families different levels evidence synteny analysis, structure prediction, and transcription translation data. This offers resource investigation biological functions

Язык: Английский

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Importance of Inter-residue Contacts for Understanding Protein Folding and Unfolding Rates, Remote Homology, and Drug Design

Molecular Biotechnology, Год журнала: 2024, Номер 67(3), С. 862 - 884

Опубликована: Март 18, 2024

Язык: Английский

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High-throughput Selection of Human de novo-emerged sORFs with High Folding Potential

Genome Biology and Evolution, Год журнала: 2024, Номер 16(4)

Опубликована: Апрель 1, 2024

De novo genes emerge from previously noncoding stretches of the genome. Their encoded de proteins are generally expected to be similar random sequences and, accordingly, with no stable tertiary fold and high predicted disorder. However, structural properties whether they differ during stages emergence fixation have not been studied in depth rely heavily on predictions. Here we generated a library short human putative varying lengths ages sorted candidates according their compactness disorder propensity. Using Förster resonance energy transfer combined Fluorescence-activated cell sorting, were able screen for most compact protein structures, as well elongated flexible structures. We find that average slightly shorter contain lower than less ones. The structures least correspond expectations more secondary structure content or higher content, respectively. Our experiments indicate older propensity compared young discuss possible evolutionary scenarios implications underlying age-dependencies proteins.

Язык: Английский

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High-throughput selection of humande novo-emerged sORFs with high folding potential

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 24, 2024

Abstract De novo genes emerge from previously non-coding stretches of the genome. Their en-coded de proteins are generally expected to be similar random sequences and, accordingly, with no stable tertiary fold and high predicted disorder. However, structural properties whether they differ during stages emergence fixation have not been studied in depth rely heavily on predictions. Here we generated a library short human putative varying lengths ages sorted candidates according their compactness disorder propensity. Using Förster resonance energy transfer (FRET) combined Fluorescence-activated cell sorting (FACS) were able screen for most compact protein structures, as well elongated flexible structures. Compact average slightly shorter contain lower than less ones. The structures least correspond expectations that more secondary structure content or higher content, respectively. Our experiments indicate older propensity compared young We discuss possible evolutionary scenarios implications underlying age-dependencies proteins.

Язык: Английский

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Modeling Length Changes in De Novo Open Reading Frames during Neutral Evolution

Genome Biology and Evolution, Год журнала: 2024, Номер 16(7)

Опубликована: Июнь 16, 2024

Abstract For protein coding genes to emerge de novo from a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and ability be transcribed. The newborn gene can further evolve accumulate changes in its sequence. Consequently, it also elongate or shrink with time. Existing literature shows that older have longer ORF, but is not clear if they elongated time remained of same length since their inception. To address this question we developed mathematical model ORF elongation as Markov-jump process, show ORFs tend keep short evolutionary timescales. We change occurs likely truncation. Our genomics transcriptomics data analyses seven Drosophila melanogaster populations are agreement model’s prediction. conclude selection could facilitate extension may explain why were observed old studies analysing scales. Alternatively, shorter purged because less yield functional proteins.

Язык: Английский

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The Hidden Bacterial Microproteome

Опубликована: Янв. 1, 2024

Язык: Английский

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