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Evolutionary causes and consequences of gene duplication

Nature Reviews Genetics (2026)Cite this article

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Abstract

Gene duplication is the primary mechanism by which new genes emerge. Models and empirical studies have shown that paralogous genes are maintained because of dosage benefits, the partitioning of ancestral functions or the acquisition of new functions. However, the underlying molecular mechanisms and the relative importance of the factors driving evolution towards one fate or another have remained difficult to quantify. Recent advances in experimental and computational methods, such as gene editing, deep mutational scanning and ancestral sequence reconstruction, have enabled molecular analyses of duplicated gene evolution across timescales. Combined, these approaches are revealing how adaptive and non-adaptive evolutionary forces shape the modern fates of gene duplicates.

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Fig. 1: The fitness effect of gene duplication and thus the fixation probability of new paralogues depends on the gene’s fitness function.
Fig. 2: Absolute dosage subfunctionalization (ADS) constrains the evolution of paralogues.
Fig. 3: Role of chance and contingency in the evolution of novel specificity.
Fig. 4: Evolution of paralogues derived from duplications of genes encoding homomeric proteins.

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Acknowledgements

The authors thank the Landry lab members for discussions during the project and thank G. Bernal Astrain and P. Venkataraman for their comments on the manuscript. C.R.L. holds the Canada Research Chair in Cellular Systems and Synthetic Biology.

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Authors and Affiliations

  1. Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Simon Aubé, Pascale Lemieux & Christian R. Landry

  2. Institut de biologie intégrative et des systèmes, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Frédéric Bédard, Simon Aubé, Pascale Lemieux & Christian R. Landry

  3. PROTEO, Le regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Frédéric Bédard, Simon Aubé, Pascale Lemieux & Christian R. Landry

  4. Centre de recherche sur les données massives, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Frédéric Bédard, Simon Aubé, Pascale Lemieux & Christian R. Landry

  5. Institut intelligence et données, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Simon Aubé, Pascale Lemieux & Christian R. Landry

  6. Département de biologie, Faculté des sciences et de génie, Université Laval, Quebec City, Quebec, Canada

    Angel F. Cisneros, Soham Dibyachintan, Frédéric Bédard, Simon Aubé, Pascale Lemieux & Christian R. Landry

  7. Centre de recherche en infectiologie, Université Laval, Quebec City, Quebec, Canada

    Frédéric Bédard

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  1. Angel F. Cisneros
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  2. Soham Dibyachintan
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  5. Pascale Lemieux
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  6. Christian R. Landry
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The authors contributed equally to all aspects of the article.

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Correspondence to Christian R. Landry.

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Glossary

Absolute dosage subfunctionalization

(ADS). A model proposing that selection acts jointly on two duplicate genes to maintain their cumulative abundance close to an optimum.

Active compensation

The modulation of the expression level of a gene in response to a change in expression or loss of function of its paralogue.

Arrival biases

The preferential fixations of genotypes because they were the first to appear out of a group of equally beneficial genotypes.

Compensatory drift

The evolution of the expression levels of paralogous genes under relaxed selection, as long as the total expression stays relatively constant.

Co-translational assembly

The formation of protein complexes during the translation of at least one the subunits, typically driven by nascent N-terminal interfaces.

Deep mutational scanning

A saturation mutagenesis technique that systematically generates every possible amino acid substitution and/or indels at every position in a sequence.

Dominant-negative mutations

Mutations that cause the loss of function of a gene and are dominant over wild-type alleles, for example, because they negatively affect function by forming inactive heteromers.

Evolutionary contingencies

Referring to the sensitivity of evolution to previous states, often resulting from the fact that mutations modify the effects of subsequent mutations.

Expression levels

The amounts of functional products produced from gene copies, resulting from the combination of transcription, translation, post-transcriptional regulation and degradation.

Expression noise

Variation in gene expression among genetically identical cells in the same environment.

Fitness function

The relationship between fitness and expression level for a gene of interest, with every point along the curve indicating the fitness value corresponding to a given expression level.

Fixation

The increase in frequency of an allele in a population to 100%.

Global epistasis

Epistasis occurring at the level of biological effects even though the substitutions behave additively with respect to the physical properties of a protein, because of a nonlinear relationship between the physical properties and the biological effects, such as fitness.

Homomers

Protein complexes composed of multiple copies of a protein produced from the same locus or allelic loci. By contrast, heteromers are protein complexes composed of protein subunits produced from different loci.

Interaction specificity

The property of a protein to selectively interact with one partner and not with others.

Neofunctionalization

Process by which one gene of a duplicate pair acquires a new function.

Paralogue interference

A phenomenon by which the binding of a protein to its paralogue alters its function and thus the effects of mutations at its locus.

Permissive mutations

Mutations that reduce the deleterious effects of other mutations. Also called compensatory mutations.

Relaxed selection

The decrease in magnitude of the fitness effects of mutations in a sequence of interest, allowing it to accumulate mutations that would have otherwise been deleterious.

Specific epistasis

Epistasis occurring because the effects of two substitutions on a phenotype combine non-additively due to local interactions.

Subfunctionalization

Process by which two duplicates partition the functions of their ancestral gene.

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Cisneros, A.F., Dibyachintan, S., Bédard, F. et al. Evolutionary causes and consequences of gene duplication. Nat Rev Genet (2026). https://doi.org/10.1038/s41576-026-00935-5

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