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Splitting pairs: the diverging fates of duplicated genes

Nature Reviews Genetics volume 3, pages 827–837 (2002)Cite this article

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.

Abstract

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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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Organismal Biology and Anatomy, The University of Chicago, 1027 East 57th Street, Chicago, 60615, Illinois, USA

    Victoria E. Prince

  2. Department of Biology, Loyola University of Chicago, 6525 North Sheridan Road, Chicago, 60626, Illinois, USA

    F. Bryan Pickett

Authors
  1. Victoria E. Prince
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  2. F. Bryan Pickett
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Corresponding author

Correspondence to Victoria E. Prince.

Related links

Related links

DATABASES

Locus Link

Abd-B

dumpy

En1

eve stripe 2

Hoxa1

Hoxa3

Hoxb1

hoxb1a

hoxb1b

Hoxb2

Hoxb3

hoxb5a

Hoxd3

Mitf

nodal

os

Sox9

SOX9

Sy

OMIM

campomelic dysplasia

Tietz syndrome

Waardenburg syndrome type 2a

The <i>Arabidopsis</i> Information Resource

AP1

CAL

FUL

ZFIN

cyc

egr2

engrailed2a

engrailed2b

mitfa

mitfb

ndr1

sox9a

FURTHER INFORMATION

F. Bryan Pickett's lab

Gene Tools LLC

PipMaker and MultiPipMaker

TRANSFAC — The Transcription Factor Database

Victoria Prince's lab

Glossary

POLYPLOIDY

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.

ALLOTETRAPLOIDY

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.

AUTOTETRAPLOIDY

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.

TELEOST

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.

REDUNDANCY

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

NON-FUNCTIONALIZATION

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

PURIFYING SELECTION

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

NEO-FUNCTIONALIZATION

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.

CONSERVED SYNTENY

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

PLEIOTROPY

When a single gene has a role in several processes.

SUB-FUNCTION

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

ALLELIC SERIES

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

GENETIC DRIFT

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

LENS CRYSTALLIN

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

DEGENERATIVE MUTATION

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

INDIVIDUAL RELATIVE FITNESS

The capacity of the individual to survive and reproduce.

EFFECTIVE POPULATION SIZE

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.

PARALOGUES

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

NEURAL CREST

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.

RHOMBOMERE

A segment of the vertebrate hindbrain (rhombencephalon).

MORPHOLINO

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

TETRASOMY

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

ORTHOLOGUES

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

ORGANIZER

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.

MADS BOX

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.

MERISTEM

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

INFLORESCENCE MERISTEM

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

STAMEN

The male, pollen-bearing organ of the plant.

ECOTYPE

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

SYNONYMOUS CHANGE

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

REPLACEMENT ALLELE

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

CLADE

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). https://doi.org/10.1038/nrg928

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