Posttranslational regulation impacts the fate of duplicated genes

Abstract

Gene and genome duplications create novel genetic material on which evolution can work and have therefore been recognized as a major source of innovation for many eukaryotic lineages. Following duplication, the most likely fate is gene loss; however, a considerable fraction of duplicated genes survive. Not all genes have the same probability of survival, but it is not fully understood what evolutionary forces determine the pattern of gene retention. Here, we use genome sequence data as well as large-scale phosphoproteomics data from the baker's yeast Saccharomyces cerevisiae, which underwent a whole-genome duplication approximately 100 mya, and show that the number of phosphorylation sites on the proteins they encode is a major determinant of gene retention. Protein phosphorylation motifs are short amino acid sequences that are usually embedded within unstructured and rapidly evolving protein regions. Reciprocal loss of those ancestral sites and the gain of new ones are major drivers in the retention of the two surviving duplicates and in their acquisition of distinct functions. This way, small changes in the sequences of unstructured regions in proteins can contribute to the rapid rewiring and adaptation of regulatory networks.

Fig. 1.

The number of protein phosphorylation sites in the pre-WGD ancestor affects the probability of gene retention in the four post-WGD yeast lineages. (A) Species tree showing the evolutionary relationships of the yeast species discussed. (B) The number of ancestral p-sites affects the fate of duplicate retention in four post-WGD lineages (S. cerevisiae, C. glabrata, S. castellii, and K. polysporus). The graph shows that the ancestors of the “retained-in-majority” bins had more p-sites than the ancestors of the “lost-in-majority” bins (S1.9) (see text for details).

Fig. 2.

Protein phosphorylation and the retention of duplicated genes. Subfunctionalization is the partitioning of p-sites among the duplicates via point mutations and stochastic reciprocal loss. A parallel or (more likely) subsequent event is neofunctionalization, the emergence of new p-sites, again via point mutations. Open boxes refer to ancestral p-sites, and solid boxes refer to recently emerged p-sites.

Fig. 3.

Inference of p-sites in the pre-WGD orthologous ancestral protein. The inference is based on alignment with pre-WGD orthologs (and ohnolog, whenever appropriate). Here, the threshold for inference is no more than two amino acid mismatches in the window of six amino acids, surrounding the p-site.