Patterns of evolutionary selection pressure in the immune signaling protein TRAF3IP2 in mammals

TRAF3 interacting protein 2 (TRAF3IP2) is important for immune responses to pathogens, inflammatory signals and autoimmunity in mammals. In the present study, we collected 19 mammalian TRAF3IP2 sequences and investigated the various types of selection pressure acting on them. Maximum likelihood estimations of nonsynonymous (dN) to synonymous (dS) substitution (dN/dS) ratios for the aligned coding sequences indicated that, as a whole, TRAF3IP2 has been subject to purifying selection. However, the N-terminus of the protein has been subject to higher selection pressure than the C-terminal domain. While eight amino acid residues within the N-terminus appear to have evolved under positive selection, no evidence for such selection was found in the C-terminus. The positively selected residues, which fall outside the currently known functional sites within TRAF3IP2, may have novel functions. The different selection pressures acting on the N- and C-terminal regions are consistent with their protein structures: the C-terminal structure is an ordered structure, whereas the N-terminus is disordered. Taken together with the results of previous studies, it is plausible that positive selection on the N-terminus of TRAF3IP2 may have occurred by competitive coevolution between mammalian hosts and viruses.     

Directionality in the evolution of influenza A haemagglutinin

The evolution of haemagglutinin (HA), an important influenza virus antigen, has been the subject of intensive research for more than two decades. Many characteristics of HA's sequence evolution are captured by standard Markov chain substitution models. Such models assign equal fitness to all accessible amino acids at a site. We show, however, that such models strongly underestimate the number of homoplastic amino acid substitutions during the course of HA's evolution, i.e. substitutions that repeatedly give rise to the same amino acid at a site. We develop statistics to detect individual homoplastic events and find that they preferentially occur at positively selected epitopic sites. Our results suggest that the evolution of the influenza A HA, including evolution by positive selection, is strongly affected by the long-term site-specific preferences for individual amino acids.