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Splitting pairs: the diverging fates of duplicated genes

Key Points

  • Genomic sequence analysis is revealing the presence of duplicated genes in all sequenced organisms.

  • Gene duplicates can arise through tandem, segmental or global duplication events.

  • In instances in which complete regulatory sequences are duplicated in concert with coding sequences, the duplicates will have highly redundant functions.

  • Classical models predict that the loss of one redundant duplicate will be the most likely evolutionary outcome, whereas the retention of two duplicates — because one takes on a new role — should happen far more rarely.

  • Sub-functionalization models might help to explain the surprising number of ancient duplicates that are retained in genomes. If each duplicate loses a complementary sub-function then both must be retained to recapitulate the complete function of the single ancestral gene.

  • Sub-functionalization relies on the inherent multifunctionality of genes, this is often provided by modular enhancers that direct specific components of gene expression patterns.

  • The duplication–degeneration–complementation (DDC) model integrates gene-level sub-functionalization with population-level evolutionary processes.

  • Species in which whole-genome duplication events have occurred, such as zebrafish and Arabidopsis, are providing useful systems to explore potential instances of degenerative complementation.

  • Sophisticated sequence analysis approaches are starting to open up the possibility of recognizing candidate cases of sub-functionalization in silico.


Many genes are members of large families that have arisen during evolution through gene duplication events. Our increasing understanding of gene organization at the scale of whole genomes is revealing further evidence for the extensive retention of genes that arise during duplication events of various types. Duplication is thought to be an important means of providing a substrate on which evolution can work. An understanding of gene duplication and its resolution is crucial for revealing mechanisms of genetic redundancy. Here, we consider both the theoretical framework and the experimental evidence to explain the preservation of duplicated genes.

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Figure 1: Phylogeny of chordates.
Figure 2: Zebrafish duplicate genes subdivide ancestral mouse Hoxb1 expression.
Figure 3: Function shuffling.
Figure 4: Mutant phenotypes of ap1 and ap1/cal plants.


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We thank A. Bruce, A. Force, R. Ho, J. Postlethwait and three reviewers for helpful comments on the manuscript. We are also grateful to D. Raible for advice on Mitf gene evolution, and to S. Santini and A. Meyer for sharing their observations before publication. Work cited from the Prince lab was funded by the National Science Foundation and that from the Pickett lab by the National Institutes of Health.

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A polyploid organism has more than two sets of chromosomes (two sets being the prevalent diploid state). For example, a tetraploid organism has four sets of chromosomes and an octaploid has eight sets.


The generation of the tetraploid state by fusion of two nuclei from different species. For example, two fertilized diploid oocytes can fuse such that the newly formed single egg has two complete sets of chromosomes.


In contrast to allotetraploidy, both sets of chromosomes are derived from the same species. This can occur in the fertilized oocyte if the nucleus divides but the cell does not.


A bony fish that belongs to the infraclass Teleostei (comprising more than 20,000 species), which includes nearly all the important food and game fish, and many aquarium fish.


When two genes can fulfil an equivalent function. Because of pleiotropy, redundancy is often partial, with two genes having overlapping rather than equivalent functions.


When one of two duplicate genes acquires a mutation in coding or regulatory sequences that ultimately renders the gene non-functional.


Selection against deleterious alleles, which will be eliminated from the population.


When one of two duplicate genes acquires a mutation in coding or regulatory sequences that allows the gene to take on a new and useful function.


(syn, same; teny, thread). Homology of gene order between two chromosomes or chromosomal segments, within or between species.


When a single gene has a role in several processes.


Any functionally discrete, independently mutable portion of a locus. For example, a cis-regulatory element, a protein domain or an alternative splice site.


A series of alleles that can be present at the same locus and that produce graded phenotypes.


The increase or decrease in allele frequencies in populations due to chance.


A protein that accumulates at high concentration in the eye and that forms the crystallin lens.


A sequence change that causes a loss of function of the affected sub-function or gene.


The capacity of the individual to survive and reproduce.


The equivalent number of breeding adults in a population after adjusting for complicating factors, such as non-random variation in family size or stochastic fluctuation in population size.


Homologous genes that are related by a duplication event. For example, mouse Hoxa2 and Hoxb2 are paralogues.


A vertebrate-specific migratory cell type that derives from the dorsal-most aspect of the neural tube and contributes to many tissues, including the peripheral nervous system and cranium.


A segment of the vertebrate hindbrain (rhombencephalon).


An antisense reagent that is able to block translation to knock down gene function.


When one chromosome in the complement is represented four times in each nucleus.


Homologous genes that are related by a speciation event. For example, mouse Hoxa1 and chick HOXA1 are orthologues.


A small dorsal region of the vertebrate gastrula-stage embryo that has the remarkable capacity to organize a complete embryonic body plan. Hilde Mangold and Hans Spemann first identified the organizer in amphibian embryos using tissue transplantation.


A highly conserved sequence motif found in a family of plant transcription factors and named after the initials of the four founder members of the family.


An undifferentiated cell population that resides at the growing tip of the roots or shoots of a plant.


An apical meristem that lies atop a shoot and that produces several, lateral flower meristems.


The male, pollen-bearing organ of the plant.


A subdivision of a species that survives as a distinct population through environmental selection and reproductive isolation.


A nucleotide change that does not alter the amino acid that is encoded.


An allele in which a mutation causes a resulting change in amino-acid identity.


A lineage of organisms or alleles that comprises an ancestor and all its descendants.

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Prince, V., Pickett, F. Splitting pairs: the diverging fates of duplicated genes. Nat Rev Genet 3, 827–837 (2002).

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