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The origin of new genes: glimpses from the young and old

Nature Reviews Genetics volume 4, pages 865–875 (2003)Cite this article

Key Points

  • The variation in the numbers of genes in different organisms indicates a general process of the origin and evolution of new genes.

  • Examining young genes is a direct approach to study this process, whereas ancient genes reveal the antiquity of some origination mechanisms.

  • Several molecular mechanisms are involved in the creation of new gene structure, among which exon shuffling, retroposition and gene duplication have been found to be particularly important.

  • A new gene in its early stage usually undergoes rapid changes in sequence, structure and expression, which indicates a continuous evolution of function.

  • A significant role of positive Darwinian selection has been detected underlying these changes and adaptive evolution might have directed the entire origination process of new genes.

  • Direct and indirect observations of new genes in eukaryotic genomes show that genes with new functions are not as rare as was previously thought.

  • Analysis of the repeated new gene origination by retroposition in the Drosophila genome has uncovered a pattern in which new genes tend to avoid the X-chromosome linkage and most of the X-chromosome-derived autosomal new genes have evolved male-specific functions. This points to the importance of genome position in new gene origination.

Abstract

Genome data have revealed great variation in the numbers of genes in different organisms, which indicates that there is a fundamental process of genome evolution: the origin of new genes. However, there has been little opportunity to explore how genes with new functions originate and evolve. The study of ancient genes has highlighted the antiquity and general importance of some mechanisms of gene origination, and recent observations of young genes at early stages in their evolution have unveiled unexpected molecular and evolutionary processes.

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Figure 1: Two examples of the accelerated evolution of new genes with new functions.
Figure 2: The biased distribution of retroposition events in the Drosophila melanogaster genome.

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Acknowledgements

We thank J. Sporfford, J. Zhang and the referees for their helpful suggestions. We also thank all members of the M.L. laboratory, past and present, for their devoted contributions to the studies on the origin of new genes and their evolution. M.L. is funded by a David and Lucile Packard Foundation Fellowship, a National Science Foundation CAREER Award and a National Institutes of Health grant.

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Authors and Affiliations

  1. Department of Ecology and Evolution, The University of Chicago, 1101 East 57th Street, Chicago, 60637, Illinois, USA

    Manyuan Long

  2. Committee on Genetics, The University of Chicago, 920 East 58th Street, Chicago, 60637, Illinois, USA

    Manyuan Long & Kevin Thornton

  3. Biology Department, University of Texas, Arlington, 76019, Texas, USA

    Esther Betrán

  4. Chinese Academy of Sciences (CAS)–Max Planck Junior Scientist Group, Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, CAS, Kunming, 650223, China

    Wen Wang

Authors
  1. Manyuan Long
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  2. Esther Betrán
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  3. Kevin Thornton
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  4. Wen Wang
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Corresponding author

Correspondence to Manyuan Long.

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DATABASES

FlyBase

Adh

Sdic

sphinx

ymp

ynd

LocusLink

DAF

PGK1

PGK2

USP6

Saccharomyces Genome Database

HXT6

HXT7

FURTHER INFORMATION

GenBank

Institute of Experimental Pathology/Molecular Neurobiology

Manyaun Long's laboratory

Molecular Population Genetics

The Genomic Scrap Yard

Glossary

NEW GENE

A gene that has originated recently in the relevant evolutionary timescale.

ECTOPIC RECOMBINATION

Recombination between nonhomologous sequences.

ILLEGITIMATE RECOMBINATION

Nonhomologous sequence recombination at the genomic DNA level.

L1 RETRO-ELEMENT

A member of the long interspersed transposable element (LINE) family, which is a type of large repetitive DNA sequence that inserts itself throughout the genome through retroposition. L1 retro-elements are ∼6,400 base pairs long and are abundant in the human genome.

ALU ELEMENT

An interspersed DNA sequence of ∼300 base pairs (bp) that is found in the genomes of primates, which can be cleaved by the restriction enzyme AluI. They are composed of a head-to-tail dimer, with the first monomer ∼140-bp long and the second ∼170-bp long. In humans, there are 300,000–600,000 copies of Alu elements.

MOBILE ELEMENTS

Also known as transposable elements. DNA sequences in the genome that replicate and insert themselves into various positions in the genome.

SUBFUNCTIONALIZATION

The process of 'partitioning' the ancestral functions of a locus among its duplicates. For example, if a single-copy gene that is normally expressed in two tissues subsequently duplicates, and each duplicate is then expressed in a different tissue, subfunctionalization has occurred.

NEOFUNCTIONALIZATION

The evolution of a new function by a duplicate gene.

PURIFYING SELECTION

Selection against deleterious alleles.

REPLACEMENT CHANGES

(Substitutions). Changes in the nucleotide sequences of coding genes that result in changes in the peptide sequence (that is, the replacement of an amino acid). These contrast with silent (or synonymous) changes in coding sequences, which do not result in changes in the peptide.

ADAPTIVE EVOLUTION

An evolutionary process that is directed by natural selection, which makes a population better adapted to live in an environment.

KA/KS

KA is the rate of substitution at non-synonymous sites and KS is the rate of substitution at synonymous sites. The ratio between the two (KA/KS) is often used to infer selection: a KA/KS that is <1 indicates a functional constraint; a KA/KS that is equal to 1 indicates a lack of functional constraint; and a KA/KS that is >1 indicates positive Darwinian selection.

POPULATION GENETIC ANALYSIS

The process of making inferences about the evolutionary and demographic history of a gene (or organism) on the basis of data on genetic variation in a species.

SELECTIVE CONSTRAINT

A limit on evolutionary change.

MCDONALD-KREITMAN TEST

A statistical test that is commonly used for the comparison of between-species divergence and within-species polymorphism at replacement and synonymous sites to infer adaptive protein evolution.

CONVERGENT EVOLUTION

Independent evolution from different ancestors that leads to similar characteristics.

NOTOTHENIOID

The most abundant group of Antarctic fish.

TRYPSINOGEN

A large diverse protein family of serine peptidases.

INTRON PHASE

The relative position of an intron within or between codons. Phase zero, one and two are defined by the position of an intron between two codons or after the first or second nucleotide of a codon, respectively.

GERMLINE INACTIVATION

The early inactivation of the sex chromosomes in germline cells in the heterogametic sex.

DOSAGE COMPENSATION

The phenomenon whereby the expression levels of sex-linked genes are made equal in males and females of heterogametic species.

XIST TRANSCRIPT

A non-coding RNA that is transcribed by an X-linked gene known as Xist (X-inactive-specific transcription), which has a role in the somatic transcriptional inactivation of one X chromosome in female mammals. This is believed to occur through the interaction of transcripts from Xist and the related gene Tsix.

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Long, M., Betrán, E., Thornton, K. et al. The origin of new genes: glimpses from the young and old. Nat Rev Genet 4, 865–875 (2003). https://doi.org/10.1038/nrg1204

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