RESUMEN
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, the pattern and rate of their evolution in protein structure over time remain unclear. Here, we addressed these issues within a surprisingly short evolutionary timescale (<1 million years for 97% of Oryza de novo genes) with comparative approaches to gene duplicates. We found that de novo genes evolve faster than gene duplicates in the intrinsically disordered regions (such as random coils), secondary structure elements (such as α helix and ß strand), hydrophobicity, and molecular recognition features. In de novo proteins, specifically, we observed an 8% to 14% decay in random coils and intrinsically disordered region lengths and a 2.3% to 6.5% increase in structured elements, hydrophobicity, and molecular recognition features, per million years on average. These patterns of structural evolution align with changes in amino acid composition over time as well. We also revealed higher positive charges but smaller molecular weights for de novo proteins than duplicates. Tertiary structure predictions showed that most de novo proteins, though not typically well folded on their own, readily form low-energy and compact complexes with other proteins facilitated by extensive residue contacts and conformational flexibility, suggesting a faster-binding scenario in de novo proteins to promote interaction. These analyses illuminate a rapid evolution of protein structure in de novo genes in rice genomes, originating from noncoding sequences, highlighting their quick transformation into active, protein complex-forming components within a remarkably short evolutionary timeframe.
Asunto(s)
Evolución Molecular , Oryza , Proteínas de Plantas , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/química , Duplicación de Gen , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
New genes (or young genes) are structural novelties pivotal in mammalian evolution. Their phenotypic impacts on humans, however, remain elusive due to the technical and ethical complexities in functional studies. Through combining gene age dating with Mendelian disease phenotyping, our research reveals a steady integration of new genes with biomedical phenotypes into the human genome over macroevolutionary timescales (~0.07% per million years). Despite this stable pace, we observe distinct patterns in phenotypic enrichment, pleiotropy, and selective pressures shaped by different gene ages. Notably, young genes show significant enrichment in the male reproductive system, indicating strong sexual selection. Young genes also exhibit functions in tissues and systems potentially linked to human phenotypic innovations, such as increased brain size, musculoskeletal phenotypes, and color vision. Our findings further reveal increasing levels of pleiotropy over evolutionary time, which accompanies stronger selective constraints. We propose a "pleiotropy-barrier" model that delineates different potentials for phenotypic innovation between young and older genes subject to natural selection. Our study demonstrates that evolutionary new genes are critical in influencing human reproductive evolution and adaptive phenotypic innovations driven by sexual and natural selection, with low pleiotropy as a selective advantage.
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T cells are a type of white blood cell that play a critical role in the immune response against foreign pathogens through a process called T Cell Adaptive Immunity (TCAI). However, the evolution of the genes and nucleotide sequences involved in TCAI is not well understood. To investigate this, we performed comparative studies of gene annotations and genome assemblies of 28 vertebrate species and identified sets of human genes that are involved in TCAI, carcinogenesis, and ageing. We found that these gene sets share interaction pathways which may have contributed to the evolution of longevity in the vertebrate lineage leading to humans. Our human gene age dating analyses revealed that there was rapid origination of genes with TCAI-related functions prior to the Cretaceous eutherian radiation and these new genes mainly encode negative regulators. We identified no new TCAI-related genes after the divergence of placental mammals, but we did detect an extensive number of amino acid substitutions under strong positive selection in recently evolved human immunity genes suggesting they are co-evolving with adaptive immunity. More specifically, we observed that antigen processing and presentation and checkpoint genes are significantly enriched among new genes evolving under positive selection. These observations reveal an evolutionary process of T Cell Adaptive Immunity that were associated with rapid gene duplication in the early stages of vertebrates and subsequent sequence changes in TCAI-related genes. These processes together suggest an early genetic construction of the vertebrate immune system and subsequent molecular adaptation to diverse antigens.
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Gene duplication is increasingly recognized as an important mechanism for the origination of new genes, as revealed by comparative genomic analysis. However, how new duplicate genes contribute to phenotypic evolution remains largely unknown, especially in plants. Here, we identified the new gene EXOV, derived from a partial gene duplication of its parental gene EXOVL in Arabidopsis thaliana. EXOV is a species-specific gene that originated within the last 3.5 million years and shows strong signals of positive selection. Unexpectedly, RNA-sequencing analyses revealed that, despite its young age, EXOV has acquired many novel direct and indirect interactions in which the parental gene does not engage. This observation is consistent with the high, selection-driven substitution rate of its encoded protein, in contrast to the slowly evolving EXOVL, suggesting an important role for EXOV in phenotypic evolution. We observed significant differentiation of morphological changes for all phenotypes assessed in genome-edited and T-DNA insertional single mutants and in double T-DNA insertion mutants in EXOV and EXOVL. We discovered a substantial divergence of phenotypic effects by principal component analyses, suggesting neofunctionalization of the new gene. These results reveal a young gene that plays critical roles in biological processes that underlie morphological evolution in A. thaliana.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Duplicación de Gen , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cromosomas de las Plantas , Regulación de la Expresión Génica de las Plantas , Genes Duplicados , Genética de Población , Mutación , Fenotipo , Plantas Modificadas Genéticamente , Análisis de Componente Principal , Selección GenéticaRESUMEN
Young, or newly evolved, genes arise ubiquitously across the tree of life, and they can rapidly acquire novel functions that influence a diverse array of biological processes. Previous work identified a young regulatory duplicate gene in Drosophila, Zeus that unexpectedly diverged rapidly from its parent, Caf40, an extremely conserved component in the CCR4-NOT machinery in post-transcriptional and post-translational regulation of eukaryotic cells, and took on roles in the male reproductive system. This neofunctionalization was accompanied by differential binding of the Zeus protein to loci throughout the Drosophila melanogaster genome. However, the way in which new DNA-binding proteins acquire and coevolve with their targets in the genome is not understood. Here, by comparing Zeus ChIP-Seq data from D. melanogaster and D. simulans to the ancestral Caf40 binding events from D. yakuba, a species that diverged before the duplication event, we found a dynamic pattern in which Zeus binding rapidly coevolved with a previously unknown DNA motif, which we term Caf40 and Zeus-Associated Motif (CAZAM), under the influence of positive selection. Interestingly, while both copies of Zeus acquired targets at male-biased and testis-specific genes, D. melanogaster and D. simulans proteins have specialized binding on different chromosomes, a pattern echoed in the evolution of the associated motif. Using CRISPR-Cas9-mediated gene knockout of Zeus and RNA-Seq, we found that Zeus regulated the expression of 661 differentially expressed genes (DEGs). Our results suggest that the evolution of young regulatory genes can be coupled to substantial rewiring of the transcriptional networks into which they integrate, even over short evolutionary timescales. Our results thus uncover dynamic genome-wide evolutionary processes associated with new genes.
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Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Endopeptidasas/genética , Células Eucariotas/metabolismo , Evolución Molecular , Retroelementos , Ribonucleasas/genética , Animales , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Redes Reguladoras de Genes , MasculinoRESUMEN
This paper has been retracted.
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Type VI secretion systems (T6SSs) translocate effector proteins, such as Rhs toxins, to eukaryotic cells or prokaryotic competitors. All T6SS Rhs-type effectors characterized thus far contain a PAAR motif or a similar structure. Here, we describe a T6SS-dependent delivery mechanism for a subset of Rhs proteins that lack a PAAR motif. We show that the N-terminal Rhs domain of protein RhsP (or VP1517) from Vibrio parahaemolyticus inhibits the activity of the C-terminal DNase domain. Upon auto-proteolysis, the Rhs fragment remains inside the cells, and the C-terminal region interacts with PAAR2 and is secreted by T6SS2; therefore, RhsP acts as a pro-effector. Furthermore, we show that RhsP contributes to the control of certain "social cheaters" (opaR mutants). Genes encoding proteins with similar Rhs and PAAR-interacting domains, but diverse C-terminal regions, are widely distributed among Vibrio species.