Trends in Genetics
Gene factories, microfunctionalization and the evolution of gene families
Introduction
The advent of the genomics era is bringing about a revolution in our ways of thinking about genome evolution. For the first time it is possible to perform detailed investigations of the sequence-level organization of eukaryotic genomes. This has brought about a revival of interest in several areas that were difficult to address by traditional molecular evolutionary techniques, and were therefore relatively neglected.
One such area is the process of gene duplication and its underlying mechanisms 1, 2. In this article, I discuss a particular class of duplicate genes, those that lie in close proximity to one another in the genome. I focus on the processes that might give rise to such gene clusters and suggest that they arise in ‘gene factories’ driven by recombinogenic sequences derived from transposable elements.
Section snippets
Gene duplication in gene and genome evolution
Duplication events in genomes can be divided into two broad classes: whole-genome duplications (WGD), in which the total chromosome complement of an organism is doubled, and segmental duplication, in which segments of a genome are duplicated [3]. At one extreme of segmental duplication is single gene duplication, which can give rise to local clusters of homologous genes. Gene clusters of this kind have been known for a long time; well-known examples include the globins [4], immunoglobulins [5],
Evolution of duplicate genes
The classical view of gene duplication is that it provides the opportunity for the evolution of new functions [2]. One way of conceptualizing this is that one copy of the duplicated gene retains its original function, whereas the second copy (generally considered to be the new copy, although it is not obvious that there is any mechanism to identify the ‘original’ version) diverges (neofunctionalization [15]). Divergence between the two copies might be at the level of protein sequence or
Mechanisms of duplication
As currently understood, there are two types of process that can give rise to gene duplication: unequal crossing-over (UCO) and transposition.
UCO takes place when two genetically similar, but nonhomologous, chromosome regions become aligned during chromosome pairing and undergo crossing-over. This results in the deletion of a region on one of the recombining chromosomes and its duplication on the other. The deleted or duplicated version of the chromosome can then become fixed in the population,
Gene factories?
We recently investigated the sequence organization of the Del36H region of the mouse genome. Del36H is a microscopically visible deletion of ∼20% of mouse chromosome 13 [27], 12.7 Mb in length, showing conserved synteny with human chromosome 6p22.1–6p22.3 and 6p25 [14]. The region is of potential interest genetically because it results in some observable phenotypes, and several disease loci map to the syntenic human region on chromosome 6p. Interestingly, the region contains several tandemly
Concluding remarks
Along with large-scale segmental duplication, it is becoming clear that tandem duplication of genes within restricted localities of the genome is an important force in genome evolution and, potentially, in the adaptive evolution both of species and gene families. It is important in this context to distinguish microfunctionalized gene families, such as those seen in the Del36H region, from fully adapted and homogeneous types. The association of high concentrations of TEs with tandem gene
Acknowledgements
I thank the Medical Research Council for financial support and Ann-Marie Mallon for useful discussions. I also thank an anonymous referee for suggestions in clarifying some aspects of the arguments presented in this article. This article describes research funded as part of the MRC UK Mouse Sequencing Consortium.
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