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De novo genes with an lncRNA origin encode unique human brain developmental functionality.

Ni A An1, Jie Zhang1, Fan Mo2,3

  • 1Laboratory of Bioinformatics and Genomic Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.

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|January 2, 2023
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Summary
This summary is machine-generated.

New human genes emerge from non-coding RNAs via RNA nuclear export mechanisms. This process, involving U1 elements and splicing, drives functional gene origin and is crucial for unique human brain development.

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Area of Science:

  • Evolutionary genetics
  • Molecular biology
  • Neuroscience

Background:

  • Human de novo genes are evolutionarily significant but their functional origin remains unclear.
  • Long non-coding RNAs (lncRNAs) are potential precursors for new genes.
  • Understanding the transition from non-coding to functional genes is critical.

Purpose of the Study:

  • To investigate the mechanisms driving the origin of de novo genes from lncRNA loci.
  • To identify sequence elements and regulatory processes involved in de novo gene emergence.
  • To explore the role of these new genes in human brain development.

Main Methods:

  • Analysis of 74 human/hominoid-specific de novo genes.
  • Identification of U1 elements and RNA splice-related sequences.
  • Functional validation of gene ENSG00000205704 in human cells and transgenic mice.
  • Assessment of neuronal maturation in cortical organoids.

Main Results:

  • Distinctive U1 elements and splice sequences facilitate RNA nuclear export and mRNA differentiation from lncRNAs.
  • Selective constraint on polymorphic sites maintains the lncRNA-mRNA boundary, enabling pre-adaptive origin of functional genes.
  • Gene ENSG00000205704 regulates nuclear export, neuronal maturation, and brain size.

Conclusions:

  • RNA nuclear export is a key mechanism in de novo gene origin.
  • Newly originated genes contribute to the unique aspects of human brain development.
  • This study provides a framework for understanding the evolution of new genes and their functional impact.