Evolution of domain promiscuity in eukaryotic genomes--a perspective from the inferred ancestral domain architectures

Abstract

Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution.

Fig. 1

The phylogenetic tree of eukaryotes used in this study adopted from ref. . Ancestral architectures were reconstructed for all nodes except for EukaryotaAME and EukUnikonts.

Fig. 2

Histogram of domain promiscuity rates averaged over domain families. Each bar represents a branch, and is labeled with the symbol corresponding to the descendant node on this branch. The rate of promiscuity change is the mean difference between the promiscuity of the descendant and the promiscuity of the ancestral node, divided by the corresponding branch length. Ancestral and contemporary genomes are colored with green and blue, correspondingly. The expected values and standard errors obtained from the permutation test are plotted in red and those branches which had p-value estimated from the permutation test less than 0.01 are marked by the asterisk.

Fig. 3

Evolution of domain promiscuity along the pathway leading to H. sapiens. X-axis represents cumulative time from the root. Y-axis represents the domain promiscuity in the corresponding ancestral genome. Shown are top tenth percentile of domains with significant correlation between promiscuity and evolution time. Functional analysis reveals that these domains are enriched in signal transduction and regulatory functions. (A) Abundance and (B) bigram network number of adjacent domains. See Table S2 (ESI†) for functional enrichment of these domains.

Fig. 4

Evolution of promiscuity for domains participating in the formation of embryonic body pattern for bilaterian subtree. For each genome, the domain promiscuity values of two different measures are presented. Empty bars correspond to domain promiscuity measures equal to zero. Small stars show that the domain’s promiscuity had the highest rate on the branch leading to the marked genome.