Domain mobility in proteins: functional and evolutionary implications

Abstract

A substantial fraction of eukaryotic proteins contains multiple domains, some of which show a tendency to occur in diverse domain architectures and can be considered mobile (or 'promiscuous'). These promiscuous domains are typically involved in protein-protein interactions and play crucial roles in interaction networks, particularly those contributing to signal transduction. They also play a major role in creating diversity of protein domain architecture in the proteome. It is now apparent that promiscuity is a volatile and relatively fast-changing feature in evolution, and that only a few domains retain their promiscuity status throughout evolution. Many such domains attained their promiscuity status independently in different lineages. Only recently, we have begun to understand the diversity of protein domain architectures and the role the promiscuous domains play in evolution of this diversity. However, many of the biological mechanisms of protein domain mobility remain shrouded in mystery. In this review, we discuss our present understanding of protein domain promiscuity, its evolution and its role in cellular function.

Figure 1:

Power-law distribution of domains in human genome. (A) Rank of a domain after sorting according the frequency in the genome on X-axis is plotted against the frequency on the Y-axis. (B) Log–log plot of the ranks of domain on X-axis is plotted against the frequency on the Y-axis.

Figure 2:

The partial domain co-occurrence graph of promiscuous domains, PH, SH3 and S_TKC in human genome. The nodes represent domains; two nodes are connected by an edge only when the connecting domains are present next to each other on the same protein sequence.

Figure 3:

Increase in promiscuous domains in 28 eukaryotic organisms (see [28] for detailed list of the organisms). The organisms are sorted with the increasing number of domain types in the genome and plotted on the X-axis. The number of promiscuous domains belonging to the five major categories in each organism is plotted on the Y-axis. Each plot represents one category; the category is mentioned on top of each plot. The goodness-of-fit measures for both linear and non-linear fit are also mentioned on top of each plot.

Figure 4:

Ancestral reconstruction of domain promiscuity in 28 eukaryotes. The tree topology is from unikont–opisthokont tree [60], and the ancestral reconstruction was created using parsimony with binary character of promiscuity for each domain. Each node is marked with a pie diagram containing gain of promiscuity in black, and loss of promiscuity in white; the gain and loss are relative to the parent node. Each pie diagram shows the fraction of domains that gained or lost promiscuity status. Additionally, each branch is colored according to the overall gain or loss in that branch; thick black lines indicate branches that gained promiscuous domains, and thick grey lines indicate branches that lost promiscuous domains.