The evolution of essential biological functions driven by new genes that reshape

由重塑的新基因驱动的基本生物功能的进化

• 批准号: 8812734
• 负责人: Grace Yuh Chwen Lee
• 金额: $ 5.42万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812734
• 关键词: Age; Alternative Splicing; Amino Acid Sequence; Binding; Biological Models; Biological Process; Birth; Code; Complex; Disease; Drosophila genus; Drosophila melanogaster; Essential Genes; Evolution; Exhibits; Fertility; Gene Expression Profile; Gene-Modified; Genes; Genome; Human; Lead; Mediating; Mutation; Nucleic Acid Binding; Nucleic Acids; Organism; Orthologous Gene; Pan Genus; Peptide Sequence Determination; Phenotype; Phylogeny; Process; Proteins; RNA Interference; RNA Splicing; Recording of previous events; Regulation; Reporting; Research; Role; Staging; Tertiary Protein Structure; Testing; Time; Tissues; fitness; gene interaction; genome-wide analysis; human disease; mRNA Precursor; novel; protein protein interaction; public health relevance

Project Summary New genes are those that originated relatively recently and are only present in a subset of species in a phylogeny. Evidence from humans and other species has demonstrated that, despite their young age, new genes can exhibit novel functions that are essential for the survival of an organism. One potential mechanism by which new genes gain essential functions is through the acquisition of many new interactions with pre-existing genes. This hypothesis is consistent with well-established observations that genes with many interaction partners are more likely to have essential functions. However, the accumulation of gene-gene interactions is, on average, a slow evolutionary process. This raises the question of how, in a short evolutionary time, new genes can acquire multiple novel interactions and how this might lead to their essential roles in the survival of an organism. The aim of this proposal is to formally test the hypothesis that new genes become essential through the acquisition of novel gene-gene interactions, and to elucidate the underlying evolutionary process. This proposed research will use Drosophila as a model system and focus on characterizing the functional importance and evolutionary history of a young gene (CG7804) that is less than four million years old and is essential for the survival of Drosophila melanogaster. CG7804 duplicated from TBPH, which is known to regulate the alternative splicing of a large set of genes in Drosophila. Unlike the evolutionarily highly conserved TBPH, CG7804 has been under strong positive selection since its origination, especially in protein domains mediating protein-nucleic acid interactions. This suggests that CG7804 likely has evolved novel essential functions through the acquisition of new interaction partners by regulating the alternative splicing of a distinct set of genes from that of TBPH. In order to test test whether CG7804 has evolved novel functions that are divergent from TBPH, this project will use tissue-specific RNA interference to compare the functional impacts of CG7804 and TBPH on D. melanogaster fitness, transcriptome regulation and alternative splicing. Nucleic acid binding profiling will identify direct functional targets of CG7804 and TBPH, enabling a formal test of the hypothesis that the acquisition of new interaction partners of new genes has led to their essentiality. Finally, ancestral CG7804 sequences will be reconstructed and functionally tested in order to identify the sequential formation of new gene-gene interactions and elucidate the dynamic process by which CG7804 became essential. This proposed research will provide a detailed functional analysis of a young gene essential for survival and, more importantly, be the first to directly characterize the underlying evolutionary processes leading to new genes' novel essential functions.

Project Summary New genes are those that originated relatively recently and are only present in a subset of species in a phylogeny. Evidence from humans and other species has demonstrated that, despite their young age, new genes can exhibit novel functions that are essential for the survival of an organism. One potential mechanism by which new genes gain essential functions is through the acquisition of many new interactions with pre-existing genes. This hypothesis is consistent with well-established observations that genes with many interaction partners are more likely to have essential functions. However, the accumulation of gene-gene interactions is, on average, a slow evolutionary process. This raises the question of how, in a short evolutionary time, new genes can acquire multiple novel interactions and how this might lead to their essential roles in the survival of an organism. The aim of this proposal is to formally test the hypothesis that new genes become essential through the acquisition of novel gene-gene interactions, and to elucidate the underlying evolutionary process. This proposed research will use Drosophila as a model system and focus on characterizing the functional importance and evolutionary history of a young gene (CG7804) that is less than four million years old and is essential for the survival of Drosophila melanogaster. CG7804 duplicated from TBPH, which is known to regulate the alternative splicing of a large set of genes in Drosophila. Unlike the evolutionarily highly conserved TBPH, CG7804 has been under strong positive selection since its origination, especially in protein domains mediating protein-nucleic acid interactions. This suggests that CG7804 likely has evolved novel essential functions through the acquisition of new interaction partners by regulating the alternative splicing of a distinct set of genes from that of TBPH. In order to test test whether CG7804 has evolved novel functions that are divergent from TBPH, this project will use tissue-specific RNA interference to compare the functional impacts of CG7804 and TBPH on D. melanogaster fitness, transcriptome regulation and alternative splicing. Nucleic acid binding profiling will identify direct functional targets of CG7804 and TBPH, enabling a formal test of the hypothesis that the acquisition of new interaction partners of new genes has led to their essentiality. Finally, ancestral CG7804 sequences will be reconstructed and functionally tested in order to identify the sequential formation of new gene-gene interactions and elucidate the dynamic process by which CG7804 became essential. This proposed research will provide a detailed functional analysis of a young gene essential for survival and, more importantly, be the first to directly characterize the underlying evolutionary processes leading to new genes' novel essential functions.

项目成果

The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster.

• DOI: 10.1371/journal.pgen.1005269
• 发表时间: 2015-06
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Lee YC