Joined: May 2002
Nucleic Acids Res. 2003 Aug 1;31(15):4401-9.
Structural diversification and neo-functionalization during floral MADS-box gene evolution by C-terminal frameshift mutations.
Vandenbussche M, Theissen G, Van de Peer Y, Gerats T.
|Frameshift mutations generally result in loss-of-function changes since they drastically alter the protein sequence downstream of the frameshift site, besides creating premature stop codons. Here we present data suggesting that frameshift mutations in the C-terminal domain of specific ancestral MADS-box genes may have contributed to the structural and functional divergence of the MADS-box gene family. We have identified putative frameshift mutations in the conserved C-terminal motifs of the B-function DEF/AP3 subfamily, the A-function SQUA/AP1 subfamily and the E-function AGL2 subfamily, which are all involved in the specification of organ identity during flower development. The newly evolved C-terminal motifs are highly conserved, suggesting a de novo generation of functionality. Interestingly, since the new C-terminal motifs in the A- and B-function subfamilies are only found in higher eudicotyledonous flowering plants, the emergence of these two C-terminal changes coincides with the origin of a highly standardized floral structure. We speculate that the frameshift mutations described here are examples of co-evolution of the different components of a single transcription factor complex. 3' terminal frameshift mutations might provide an important but so far unrecognized mechanism to generate novel functional C-terminal motifs instrumental to the functional diversification of transcription factor families.|
From the discussion:
|Based on these observations and the results presented here, we propose a model for the functional diversification of duplicated members of transcription factor families (Fig. 5). After duplication of an ancestral gene X, one of the copies (Y) may accumulate mutations in the C-terminus, while retaining features such as DNA binding, essential for its function as a transcription factor, in the upstream coding regions. Apart from in frame insertions/deletions and single nucleotide substitutions, mutations in the coding sequence at the 3' end will also induce frameshifts, as such masking the ancestral origin of the motif at the protein level. While most frameshift mutations will be deleterious for the existing function, in specific cases they may yield novel functional C-terminal motifs. The three cases we have described are perfect examples of such a neo-functionalization process. This widens the emerging view that plant transcription factors evolve mainly by changes in cis-regulatory elements that affect their expression pattern (37,38), and that after gene duplication, mainly degeneration and selection of complementary functioning, i.e. sub-functionalization occurs (39,40). At first sight, it may seem extraordinary that in all three cases, frameshift mutations of highly conserved motifs yielded novel highly conserved motifs. However, this specific situation is the only type of motif generation that can still be recognized after millions of years of independent evolution of both copies. If the new motif had been recruited from a sequence in a non-conserved (Y3 and Y4, Fig. 5) or less conserved region of the C-terminus (e.g. Y2), it would be impossible to trace back the ancestral motif. Equally important, either the new or the ancestral motif must contain amino acid residues that are not too highly degenerate in order to be able to recognize the related motif after frameshifting. Thus, the only cases of frameshift mutations that we still can recognize are those in highly conserved motifs that yield novel highly conserved motifs. Finally, novel motifs may be acquired in an additive way downstream of existing motifs as an extra feature, with retention of the ancestral motif that in such a case becomes internal (e.g. Y3); or with subsequent loss of the ancestral motif (all other cases). |
|Figure 5. Model for the generation of novel C-terminal motifs within the MADS-box gene family. After duplication of an ancestral gene X, the Y copy accumulates mutations in the C-terminal domain, while retaining the essential MIK domain. Insertions or deletions will cause a frameshift in the coding sequence. Rarely, these frameshift mutations may yield novel functional motifs that consequently will be conserved. In cases where the novel motif is recruited from poorly conserved regions (e.g. Y 2–4) in the ancestral sequence, the sequence relation with the ancestral gene X will become unclear after a period of independent evolution. In the Y copy, new motifs may be added downstream of the ancestral motif as an extra feature, with retention of the ancestral motif which in this case becomes internal (e.g. Y3); or with subsequent loss of the ancestral motif (all other cases).|
...other good stuff in the paper too long to reproduce here.