Analysis of C3 suggests three periods of positive selection events and different evolutionary patterns between fish and mammals

Abstract

Background: The third complement component (C3) is a central protein of the complement system conserved from fish to mammals. It also showed distinct characteristics in different animal groups. Striking features of the fish complement system were unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. The evidences of the involvement of complement system in the enhancement of B and T cell responses found in mammals indicated that the complement system also serves as a bridge between the innate and adaptive responses. For the reasons mentioned above, it is interesting to explore the evolutionary process of C3 genes and to investigate whether the huge differences between aquatic and terrestrial environments affected the C3 evolution between fish and mammals.

Methodology/principal findings: Analysis revealed that these two groups of animals had experienced different evolution patterns. The mammalian C3 genes were under purifying selection pressure while the positive selection pressure was detected in fish C3 genes. Three periods of positive selection events of C3 genes were also detected. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history.

Conclusions/significance: Three periods of positive selection events had happened on C3 genes during history and the fish and mammals C3 genes experience different evolutionary patterns for their distinct living environments.

Figure 1. The putative gene tree for C3 reconstructed by Bayesian approach with no constraints on the topology.

The Darwin selection pressures were detected by the branch-site models in the ancestral lineages to vertebrates (in green), mammals (in red) and ostariophysian together with protacanthopterygian (Ost+Pro) fishes (in blue). The positive selected sites with posterior probabilities larger than 0.95 (PP>0.99 in bold) were showed on the corresponding lineages. The synonymous substitution (d _N), non-synonymous substitution (d _S) of nucleotides and the ratio of d _N/ d _S of these ancestral lineages were showed. The sequences of mammalian (red) and fish C3 (blue) were then tested by site-model tests in next analysis, respectively.

Figure 2. Sliding window analysis of variation in omega value along fish and mammalian C3 genes.

It was set to be 90 bp for the window size and 36 bp for the step size. Beneath the plot is a schematic of the C3 gene, which illustrates the distribution of the characteristic domains.