The evolution of gene duplications: classifying and distinguishing between models

Key Points

  • Models of gene duplication can be classified into four major categories according to the mode of selection in the early phases of the evolution of the duplicated copies.

  • The evolutionary and population genetic assumptions for each model are described in this Review.

  • Many models show that under certain conditions, a newly arisen duplicated copy of a coding gene can be stably maintained by selection after it is fixed in the population.

  • Summaries of several models for the evolution and maintenance of gene duplications are provided. They have different evolutionary predictions in the phases before the final fate of the duplicated copy is determined.

  • The necessary data and the experimental designs to obtain such data that are needed to distinguish between the different models are described. The synonymous–non-synonymous ratio of divergence between duplicated copies is not informative for distinguishing between different models.

  • A pertinent issue in the evolution of gene duplications is the role of selection in their fixation. To resolve this issue, it is necessary to obtain polymorphisms in and around copy-number variants.

  • Gene conversion between duplicates plays an important part in the early stages of the evolution of duplicated genes, depending on the model in question, and can promote or inhibit the maintenance of the gene copy.

Abstract

Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications.

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Figure 1: Phases leading to the stable preservation of a duplicated gene.
Figure 2: Illustration of the models in categories I, II and III for gene-duplication evolution.

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Acknowledgements

We thank M. Lynch for insightful comments on the manuscript.

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Glossary

Gene duplication

The emergence of a heritable copy of a gene.

Neofunctionalization

The random acquisition of a new function in the course of the accumulation of neutral mutations in duplicated genes.

Subfunctionalization

The process of the accumulation of degenerate mutations in gene copies that subdivides gene function among the duplicated genes. This term has been introduced to describe the mechanism of the duplication–degeneration–complementation model, but it is often used indiscriminately to describe any subdivision of function.

Specialization

A process of improvement of different aspects of gene function in each gene copy, which is driven by positive selection.

Non-functionalization

The process of the accumulation of neutral mutations in a duplicated gene that renders the gene copy non-functional. Also known as pseudogenization.

Degenerate mutation

A mutation that does not affect fitness but is damaging to gene function.

Promiscuous function

A secondary, possibly neutral function that is performed by a protein with another primary function. It is an example of gene sharing.

Gene sharing

An early term describing situations in which a gene has more than one function. Modern studies describe such genes as multifunctional.

Gene dosage

The amount of product produced from a gene; broadly equivalent to gene expression.

Gene amplification

The emergence of a non-heritable extra copy of a gene in a somatic tissue. In microorganisms this term can be used interchangeably with gene duplication.

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Innan, H., Kondrashov, F. The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11, 97–108 (2010). https://doi.org/10.1038/nrg2689

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