Model organisms: Fish

29/8/02. By Richard Twyman

Two species of fish are widely used as model organisms: the zebrafish primarily because of its experimental and genetic amenability, and the pufferfish because of its extraordinarily compact genome.

Zebrafish (Danio reiro)

The zebrafish comes close to being the ideal model organism for vertebrate development because it appears to combine the best features of all the other models.

Like the frog , zebrafish embryos develop externally and can be viewed and manipulated at all stages. However, zebrafish development is more rapid than in the frog, the organisation of the embryo is simpler and (like worms and fruit flies ) the embryo is transparent. Like the mouse , the zebrafish is amenable to genetic analysis and has a similar generation interval (2-3 months). However, zebrafish are smaller than mice and they produce more offspring in a shorter time. A female zebrafish can lay up to 200 eggs per week, while a mouse may produce a litter of up to 15 embryos in 21 days.

It is easy to induce new mutations in zebrafish and large-scale screens have been carried out to identify mutations causing defects in particular biological processes, such as the developing nervous system. The technology for gene transfer to zebrafish is highly advanced (also Transgenic mice ).

These advantages have allowed the creation of dense genetic maps in the zebrafish, which have been useful for the comparative mapping of human genes (see Comparative genomics ). There is extensive similarity between the zebrafish and human genomes so many human developmental and disease genes have counterparts in the zebrafish. The zebrafish genome is 1700 million base pairs in length, about half the size of the human genome.

A number of zebrafish mutants have been produced that are good models of human diseases, and can therefore be used to test candidate drugs. These include models of Alzheimer's disease, congenital heart disease, polycystic kidney disease and cancer.

The zebrafish (Danio reiro) is amenable to genetic analysis and has a generation interval of 2 to 3 months.

The Japanese medaka (Oryzias latipes) has similar properties to the zebrafish and is preferred in some laboratories.

Japanese pufferfish (Fugu rubripes)

The Japanese pufferfish has become a model organism because it has the shortest genome of any known vertebrate – just 400 million base pairs, representing about 25 per cent of the zebrafish genome or 10-15 per cent of the human genome. Despite its brevity, the pufferfish genome contains a similar number of genes to the human genome. However, the genes are organised differently, with smaller introns, less spacer DNA between the genes and an almost total absence of repetitive DNA. The compactness of the pufferfish genome simplifies the detection and analysis of genes and their regulatory elements.

The pufferfish genome sequence was published in 2002 and was only the second vertebrate genome to be completed (the human genome was the first). The entire genome was assembled using the shotgun sequencing method, over 30 000 genes were identified, and comparative genomics helped to reveal more than 1000 human genes that had not previously been recognised. As for the mouse and zebrafish genomes, there are large regions of synteny (conserved gene order) between pufferfish and human beings.

Further reading

Feature: Why the fish?

Aparicio S et al. Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 2002 Aug 23;297(5585):1301-10. Abstract