Trends in Genetics
Subfunction partitioning, the teleost radiation and the annotation of the human genome
Section snippets
A genome duplication in the lineage of ray-finned fish
Pioneering studies revealed that zebrafish often has two orthologs (see Glossary) of human genes 4, 5 (for recent lists see Refs 6, 7). Genetic mapping studies showed that zebrafish co-orthologs (special types of paralogs) of human genes generally occupy duplicated segments on different zebrafish chromosomes 8, 9, 10, 11, 12, 13, 14, 15, 16, 17. Did most zebrafish duplicated chromosome segments arise by segmental duplication as in the human genome [18], or by genome duplication [19]? Consider,
When did genome duplication occur in the lineage of ray-finned fish?
The same early work that provided a mechanism for the expansion of zebrafish gene families also provided evidence as to when the duplication event took place 8, 9. Amores et al. [8] showed that among the four pufferfish (Fugu: Takifugu rubripes) Hox clusters known at the time [26], one was orthologous to the zebrafish hoxaa cluster, one to the hoxab cluster and the other two to the hoxba and hoxca clusters. This implied that the event that produced duplicate copies of zebrafish hox clusters
Evolution of gene duplicates in teleost fish
The teleost genome duplication presents previously unanticipated advantages for the analysis of gene function because of principles that govern the evolution of gene duplicates. After genome duplication, each gene copy can follow a separate evolutionary trajectory, little affected by unequal recombination or gene conversion, which homogenize tandem duplicates [48]. In the classical model [2], new gene duplicates face one of two fates: either one copy mutates to a pseudogene (called
Evidence for subfunction partitioning
Although it can be difficult to demonstrate that any particular pair of gene duplicates was retained by subfunctionalization, subfunction partitioning is common among duplicated genes arising from the preteleost genome duplication event. Subfunction partitioning can involve regulatory and/or structural subfunctions and has important evolutionary consequences. Assume, for instance, that an ancestral gene is expressed in liver and brain from independently mutable regulatory elements, and that
Nonfunctionalization, subfunction partitioning and lineage divergence
What has been the role of duplicate gene evolution in the teleost radiation? Different genes could have experienced nonfunctionalization in different teleost lineages (called divergent resolution in Ref. [73]). For example, the zebrafish lineage maintained two copies of the hoxc complex, but the pufferfish and medaka lineage retained just a single copy of the hoxccomplex, whereas the reverse is true for the hoxd complex 8, 29, 30, 45. An open question is to what extent such lineage-specific
Has subfunction partitioning occurred differently in various teleost lineages?
To evaluate the extent to which diverse teleost lineages have actually partitioned ancestral subfunctions differentially, we must examine the functions of both co-orthologs in more than one teleost. Gene expression patterns can serve as surrogates for regulatory subfunctions, but unfortunately, we know the detailed expression patterns of both duplicates in two different teleosts in very few cases. For MITF, most subfunctions appear to have partitioned before the divergence of zebrafish and
Subfunction partitioning can help identify genetic regulatory elements
Subfunction partitioning of teleost genes provides a special opportunity to identify tissue-specific regulatory elements. Because of the antiquity of their divergence, teleosts and tetrapod genome sequences have randomized except where function constrains sequence. Thus, conserved noncoding (CNC) sequences suggest functional genomic elements [78], and these sequences can be verified in functional tests [79]. Convenient computer programs are now available to identify CNC elements 80, 81. When
Subfunction partitioning in teleosts can facilitate analysis of gene function
Besides providing fundamental insights into the evolution of gene function, the origin of biodiversity, and analysis of conserved noncoding DNA, subfunction partitioning provides distinct advantages for functional genetic analyses. These include the identification of gene functions obscured in mammals by either pleiotropy or haploinsufficiency.
Many genes are essential at several developmental stages. Null mutations in such genes will block development at the stage of the earliest essential
Conclusions
Recent evidence converges on the conclusion that a genome duplication event preceded the grand radiation of teleosts into the most species-rich group of vertebrates. Subfunction partitioning could be a universal evolutionary pathway followed by co-orthologs resulting from this event, and perhaps by duplicated genes in general. It is still unclear how often teleost co-orthologs have partitioned subfunctions and how often they have evolved novel functions. A consequence of subfunction
Glossary
- Allotetraploid:
- a hybrid individual with two haploid genomes from one species and two haploid genomes from a different species.
- Autotetraploid:
- an individual with four haploid genomes all from the same species.
- Co-orthologs:
- a set of at least three genes in two species that are derived from a single gene in the last common ancestor of the two species, followed by gene duplication in the lineage of at least one of the species after the two species diverged. Co-orthology represents a special case of
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