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Comparative genomics at the vertebrate extremes

Nature Reviews Genetics volume 5, pages 456–465 (2004)Cite this article

Key Points

  • Distant species comparisons reveal core vertebrate sequences that often function as enhancers.

  • Sequences that are conserved across long evolutionary distances often occur in clusters.

  • Distant species comparisons enable the analysis of a limited subset of genes in the human genome. These genes often have pivotal roles in embryonic development.

  • Comparisons of multiple primate species enable the identification of primate-specific conserved sequences.

  • Comparisons between human and chimpanzee sequences reveal sequence changes that underlie human-specific adaptations.

  • The sequences of many additional vertebrate genomes, as well as extensive information about human sequence polymorphisms, will become available in the near future, which could significantly change the approach to comparative genomics.

Abstract

Annotators of the human genome are increasingly exploiting comparisons with genomes at both the distal and proximal evolutionary edges of the vertebrate tree. Despite the sequence similarity between primates, comparisons among members of this clade are beginning to identify primate- as well as human-specific functional elements. At the distal evolutionary extreme, comparing the human genome to that of non-mammal vertebrates such as fish has proved to be a powerful filter to prioritize sequences that most probably have significant functional activity in all vertebrates.

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Figure 1: Architecture of human–Fugu rubripes conserved non-coding sequences in the human genome.
Figure 2: Sonic hedgehog expression in the limbs is regulated by an enhancer at a distance of 1 Mb.

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Acknowledgements

We would like to thank Len Pennacchio and members of the Rubin laboratory for useful discussions. Research was conducted at the E. O. Lawrence Berkeley National Laboratory, with support by a grant from the Programs for Genomic Application, NHLBI, and performed under a Department of Energy contract, University of California, USA.

Author information

Authors and Affiliations

  1. DOE Joint Genome Institute, Walnut Creek, 94598, California, USA

    Dario Boffelli, Marcelo A. Nobrega & Edward M. Rubin

  2. Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    Dario Boffelli, Marcelo A. Nobrega & Edward M. Rubin

Authors
  1. Dario Boffelli
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  2. Marcelo A. Nobrega
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  3. Edward M. Rubin
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Correspondence to Edward M. Rubin.

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Related links

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DATABASES

Entrez

DACH

even skipped

Hoxb4

LMBR1

LPA

MEF2C

Shh

FURTHER INFORMATION

Encode

Gene Ontology Consortium database

SHADOWER

VISTA Tools

Glossary

NEUTRAL RATE

Genetic variation that does not affect the fitness of the organism is not subject to selection and evolves at the neutral rate.

GENE DESERTS

Gene-poor regions in the genome that are larger than 500 kb. Gene deserts often contain sporadic evidence of transcription.

VISTA

A powerful tool for aligning the genome and visualizing the location of conserved sequences (see online links box).

PHYLOGENETIC SHADOWING

An approach that combines comparisons of sequences from multiple, closely related species with a molecular phylogenetic model of sequence evolution to identify significantly conserved elements.

POSITIVE SELECTION

A sequence change in a species that results in increased fitness is subject to positive selection. As a consequence, the change normally becomes fixed, leading to adaptive evolution of that species.

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Boffelli, D., Nobrega, M. & Rubin, E. Comparative genomics at the vertebrate extremes. Nat Rev Genet 5, 456–465 (2004). https://doi.org/10.1038/nrg1350

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