Evolutionary genetics: When duplicated genes don't stick to the rules

Abstract

A common assumption among biologists, and one that we teach our students, is that orthologous genes (ie homologous genes in two different species) have identical or highly similar functions, while paralogs (ie genes created by duplication within a species) will evolve different functions. However, in a recent paper in Current Biology, Causier et al (2005) describe exceptions to this pattern, which provide a challenge to our understanding of the evolution of multigene families. Recent analyses of genome sequences have revealed that gene duplication has been rampant. The creation of extra gene copies can occur by unequal crossing over, reverse transcription, or even the duplication of entire genomes. It has now been generally accepted that such duplication events have been crucial for adaptive radiations of species and the general increase of genetic and biological complexity (Maere et al, 2005). The consequence of all these duplications is that, in many eukaryotes, the majority of genes occur in more than one copy and so form gene families, some comprising tens or even hundreds of genes. It is important to decide on the correct homology relationships when comparing gene families in different species. In simple models of gene family evolution, after a duplication event, one of the gene copies is assumed to be redundant and freed from functional constraints, and therefore able to evolve a new function (Ohno, 1970). So whereas orthologs tend to have the same function in different species, paralogs can evolve different functions (see Figure 1a). An exception to this rule, described in this new paper, comes from C-function genes in two model plants: the thale cress, Arabidopsis thaliana, and the snapdragon, Antirrhinum majus. In the generally accepted ABC model of flower development (Coen and Meyerowitz, 1991), the C-function genes are responsible for the specification of male and female reproductive organs. Mutants in the C-function genes cause reproductive organs to develop into nonreproductive perianth organs. In Arabidopsis, the classical C-function gene encodes a homeotic MADS-box transcription factor called AGAMOUS (AG). Previous analyses based on phylogenetic tree construction have shown that a gene called FARINELLI (FAR) is the ortholog of AGAMOUS in Antirrhinum. The orthologous relationship between both genes was again confirmed in this new study based on genome colinearity, that is, by comparing the gene content and order of the two genomes. However, although both genes are unambiguously orthologs, they have clearly different functions. Nevertheless, a functional homolog of AGAMOUS in Antirrhinum does exist; a gene called PLENA (PLE), which is actually a paralog of FARINELLI that originated through a gene duplication event that occurred about 125 million years ago in a common ancestor of Arabidopsis and Antirrhinum. In turn, PLE has an ortholog in Arabidopsis, called SHATTERPROOF (SHP) (Figure 1b), which, like FAR, has a different function from its ortholog. Thus, although FAR is the ortholog of AG, and SHP is the ortholog of PLE, the functional homolog of AG is PLE, and not, as would be expected, FAR. Duplicated genes can diverge in function in at least two different ways. The first way is through the accumulation of amino-acid changes in the protein-coding domain itself. Although such changes can indeed lead to genes with new functions or subfunctions, clear examples of such functional divergence are still quite rare. A second way is through changes in the noncoding regulatory elements of the duplicate. One model that describes such changes and that has become increasingly popular in the last few years is the subfunctionalization model proposed by Force et al (1999). This model starts