How do proteins gain new domains?

Abstract

A study of the contributions of different mechanisms of domain gain in animal proteins suggests that gene fusion is likely to be most frequent.

Figure 1

Possible mechanisms for the gain of protein domains. Colored blocks represent exons, with red, blue and green indicating exons coding for different domains. Solid black lines represent introns and red lines indicate intergenic regions. (a) Gene fusion. The noncoding region between two genes is modified so that the exons of the first gene become spliced with the second. (b) Exon extension. The noncoding region following an exon becomes part of the exon and codes for a new domain. (c) Exon recombination. The exons of two genes become directly joined. (d) Intron recombination. An exon from one gene is inserted into the intron of another. (e) Retroposition. A retrotransposon sequence (RT, purple) mediates the copying of itself and a neighboring gene region via an mRNA intermediate, followed by insertion into another gene.

Figure 2

Hypothetical model of a multidomain protein gaining an intrinsically disordered region via a carboxy-terminal exon extension. This protein has three folded domains (based on Protein Data Bank entry 1BIB), colored yellow, blue and red, and a 40-residue disordered extension at its carboxyl terminus, colored green. The folded domains are shown as a surface representation, and the disordered region is shown as an ensemble model with multiple distinct structures representing its substantial conformational heterogeneity.