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Cited by 38Chromosomal and Genetic VariationsGenomics and Phylogenetic StudiesEvolution and Genetic Dynamics

De Novo Genes

Open access
Zhao, Li, Svetec, Nicolas, Begun, David J.·2024·Annual Review of Genetics
DOI 10.1146/annurev-genet-111523-102413PMC PMC12051474
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Abstract

Although the majority of annotated new genes in a given genome appear to have arisen from duplication-related mechanisms, recent studies have shown that genes can also originate de novo from ancestrally nongenic sequences. Investigating de novo–originated genes offers rich opportunities to understand the origin and functions of new genes, their regulatory mechanisms, and the associated evolutionary processes. Such studies have uncovered unexpected and intriguing facets of gene origination, offering novel perspectives on the complexity of the genome and gene evolution. In this review, we provide an overview of the research progress in this field, highlight recent advancements, identify key technical and conceptual challenges, and underscore critical questions that remain to be addressed.

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Integrity signals

Registry

Crossref · 10.1146/annurev-genet-111523-102413

Cites

170 of 170 references verified0 citation errors · 0 not checkable

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  • A gene that initially does not confer a selective advantage may become more common simply by chance.

    “A gene that initially does not confer a selective advantage may become more common simply by chance, and if it later acquires a useful function, it may become subject to positive selection [61].”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [61]

    The Population Genetic Approaches section (page unavailable) reports evidence suggestive of positive selection on the spread of de novo genes. It does not say that a gene lacking an initial selective advantage can become more common by chance and later acquire a useful function. The De Novo Gene Loss section discusses drift as a possible cause of gene loss, not the increase described here. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Genetic drift can lead to the fixation of "passive" genes, which may later acquire important functions or become subject to selection.

    “This stochastic process can lead to the fixation of “passive” genes, which may later acquire important functions or become subject to selection.”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [61]

    The Functions of De Novo Genes section says de novo genes may become fixed, and the Comparative Approaches section reports evidence of function and selection in older de novo genes. But our copy does not say that genetic drift fixes “passive” genes that later acquire functions or become subject to selection; the fixation passage instead discusses genomic conflict. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Genetic drift can be particularly significant in isolated or small populations, where the effect of random sampling is more pronounced.

    “Genetic drift can be particularly significant in isolated or small populations, where the effect of random sampling is more pronounced.”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [61]

    The section on Population Genetic Effects on De Novo Gene Dynamics says selection may be less effective in species with smaller effective population sizes, and De Novo Gene Loss discusses loss by drift. Neither passage states that drift is particularly significant in small or isolated populations because random sampling has a stronger effect there; the paper supports only part of the attributed point. Page numbers were not available in our copy. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • If a gene that initially does not confer a selective advantage later acquires a useful function, it may become subject to positive selection.

    “A gene that initially does not confer a selective advantage may become more common simply by chance, and if it later acquires a useful function, it may become subject to positive selection [61].”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [61]

    The Population Genetic Approaches section (page unavailable) says that patterns among segregating Drosophila de novo genes suggest positive selection can contribute to their spread. It does not describe the claimed sequence in which a gene initially lacks a selective advantage, spreads by chance, and later acquires a useful function that brings it under positive selection. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • In some circumstances, especially in small populations, a neutral or nearly neutral gene can fix even in the absence of selective advantages through genetic drift.

    “In some circumstances, especially in small populations, a neutral or nearly neutral gene can fix even in the absence of selective advantages through genetic drift.”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [61]

    The Population Genetic Effects on De Novo Gene Dynamics section says smaller effective populations may have higher de novo gene birth rates and less effective selection for fixing slightly beneficial genes. The De Novo Gene Loss section discusses loss by drift, not fixation by drift. Searches for neutral or nearly neutral gene fixation found no passage stating that such genes can fix without a selective advantage, especially in small populations; page numbers were unavailable. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cites

Flagged first, then by citations

Research works printed but not linked: 6

  1. [51]Gubala AM, Schmitz JF, Kearns MJ, Vinh TT, Bornberg-Bauer E, 2017. The Goddard and Saturn genes are essential for Drosophila male fertility and may have arisen de novo. Mol. Biol. Evol. 34(5): 1066– 82 28104747 PMC5400382
  2. [63]Kelley M, Wu D, Fay RR. 2006. Development of the Inner Ear. New York: Springer
  3. [67]Knopp M, Gudmundsdottir JS, Nilsson T, König F, Warsi O, 2019. De novo emergence of peptides that confer antibiotic resistance. MBio 10(3): e00837– 19 31164464 PMC6550523
  4. [101]Ohno S 1970. Evolution by Gene Duplication. Berlin/Heidelberg, Ger.: Springer
  5. [152]Wang Y, Tang X, Lu J. 2023. Convergent and divergent evolution of microRNA-mediated regulation in metazoans. Biol. Rev. Camb. Philos. Soc. 99(2): 525– 45 37987240
  6. [175]Zhou Q, Zhang GG-J, Zhang Y, Xu S, Zhao R, 2008. On the origin of new genes in Drosophila. Genome Res. 182007: 1446– 55 PMC2527705 18550802

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Authors
Zhao, L., Svetec, N., & Begun, D. J.
Affiliations
  • Rockefeller University (US)
  • University of California, Davis (US)
ORCID
Venue
Annual Review of Genetics
Publisher
Annual Reviews
Published
2024-11-25
Volume
58
Issue
1
Pages
211-232
ISSN
  • 0066-4197 (ISSN-L)
  • 1545-2948
DOI
10.1146/annurev-genet-111523-102413
PMC
PMC12051474
OpenAlex
W4401206157
Cited by
38
References
170
Citations by year
2026: 15 · 2025: 22 · 2024: 1
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Annual Review of Genetics (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by)
Funders
National Institute of General Medical Sciences (R35GM134930, R35GM133780)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
de novo genes, gene origin, gene evolution, gene duplication, regulatory mechanisms, genome complexity
MeSH terms
Animals, Humans, Genome, Evolution, Molecular, Gene Duplication, Genomics

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