Turning a hobby into a job: How duplicated genes find new functions

Key Points

  • Natural selection uses duplicated genes as raw material for functional innovation, co-opting their existing features to new functions.

  • Understanding genetic innovation requires two questions to be addressed: which gene was involved in the duplication; and how has natural selection acted on that duplication to optimize the novel function?

  • Genes with functions such as enzymes, transporters and transcription factors often survive in duplicate. However, the mechanism of duplication is important: genes that are part of complex cellular networks are more easily duplicated by whole-genome duplication (WGD) than by small-scale duplication (SSD).

  • In order to have the potential to acquire a new function, a duplicate gene must come under the protection of natural selection so that it is not eliminated by degenerative mutations. At least three mechanisms can allow natural selection to preserve a duplicate gene pair: neofunctionalization, subfunctionalization and selection for gene dosage.

  • Strikingly, all three of the above mechanisms have been involved in the appearance of novel functions. For instance, dosage selection can maintain a gene duplication in order to provide sufficient expression of a gene product with a weak but beneficial new activity.

  • Such existing minor activities in genes might or might not be related to the gene's evolved function. Examples include enzymes with minor activities for substrates related to their primary substrate, and receptors with affinities for several ligands.

  • Subfunctionalization can also be involved in the process of generating novelty. An example is the GAL1GAL3 gene duplication in Saccharomyces cerevisiae, in which a single gene first gained a novel function that was then optimized by duplication and adaptive subfunctionalization.

Abstract

Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes can originate in several different ways, including mutations that directly impart new functions, subdivision of ancestral functions and selection for changes in gene dosage. Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.

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Figure 1: Potential fates of duplicate genes.
Figure 2: Hypothetical example of network evolution following a genome duplication.
Figure 3: The isoleucine and valine biosynthetic pathways in Saccharomyces cerevisiae.
Figure 4: Divergence of the aldosterone and cortisol receptors in tetrapods.
Figure 5: Subfunctionalization of a galactose catabolism gene regulatory circuit in Saccharomyces cerevisiae.

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Acknowledgements

We thank K. Byrne, B. Cusack, J. Gordon, N. Khaldi, and J. Mower for discussions regarding the fates of duplicated genes. We would also like to thank three anonymous reviewers for critical comments. This work was supported by Science Foundation Ireland.

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Correspondence to Kenneth H. Wolfe.

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Glossary

Subfunctionalization

A pair of duplicate genes are said to be subfunctionalized if each of the two copies of the gene performs only a subset of the functions of the ancestral single copy gene.

Genetic drift

Random fluctuations through time in the allele frequencies of a population, caused by a sampling effect in small populations. Drift can overcome the effects of natural selection if the selective differences between alleles are small.

Neofunctionalization

A pair of duplicate genes in a population are said to be neofunctionalized if one of the two genes possesses a new, selectively beneficial function that was absent in the population before the duplication.

Retrotransposed

Describes a gene that has undergone duplication through a process that involves an mRNA intermediate. It occurs when a reverse transcriptase enzyme synthesizes DNA from an mRNA template and the DNA is then integrated into the genome. Because retrotransposition usually uses mature mRNAs as a substrate, the resulting duplicate genes often lack introns.

Degree distribution

The degree of a node in a network (in this case, a gene) is the number of interactions it has with other nodes in the network. Thus, in a protein–protein interaction network, the degree of a gene is the number of proteins that the product of the gene interacts with. The degree distribution of a network describes the frequency of nodes in that network with a given degree: many networks of biological interest show a power-law degree distribution.

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Conant, G., Wolfe, K. Turning a hobby into a job: How duplicated genes find new functions. Nat Rev Genet 9, 938–950 (2008). https://doi.org/10.1038/nrg2482

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