Convergence of Domain Architecture, Structure, and Ligand Affinity in Animal and Plant RNA-Binding Proteins.
Reconstruction of ancestral protein sequences using phylogenetic methods is a powerful technique for directly examining the evolution of molecular function. Although ancestral sequence reconstruction (ASR) is itself very efficient, downstream functional, and structural studies necessary to characterize when and how changes in molecular function occurred are often costly and time-consuming, currently limiting ASR studies to examining a relatively small number of discrete functional shifts. As a result, we have very little direct information about how molecular function evolves across large protein families. Here we develop an approach combining ASR with structure and function prediction to efficiently examine the evolution of ligand affinity across a large family of double-stranded RNA binding proteins (DRBs) spanning animals and plants. We find that the characteristic domain architecture of DRBs-consisting of 2-3 tandem double-stranded RNA binding motifs (dsrms)-arose independently in early animal and plant lineages. The affinity with which individual dsrms bind double-stranded RNA appears to have increased and decreased often across both animal and plant phylogenies, primarily through convergent structural mechanisms involving RNA-contact residues within the β1-β2 loop and a small region of α2. These studies provide some of the first direct information about how protein function evolves across large gene families and suggest that changes in molecular function may occur often and unassociated with major phylogenetic events, such as gene or domain duplications.
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ.
Raquel
R
Dias
Department of Microbiology & Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
Austin
A
Manny
Department of Microbiology & Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
Oralia
O
Kolaczkowski
Department of Microbiology & Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.|Genetics Institute, University of Florida, Gainesville, FL.
Bryan
B
Kolaczkowski
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D005075:Biological Evolution; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D008024:Ligands; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D010940:Plant Proteins / Q000235:genetics; D010944:Plants / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D000072417:Protein Domains; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D013329:Structure-Activity Relationship
D008024:Ligands; D010940:Plant Proteins; D016601:RNA-Binding Proteins
RNA interference; ancestral sequence reconstruction; double-stranded RNA binding proteins; molecular functional evolution; protein family evolution