Characterizing lineage-specific evolution and the processes driving genomic diversification in chordates

Abstract

Background: Understanding the origins of genome content has long been a goal of molecular evolution and comparative genomics. By examining genome evolution through the guise of lineage-specific evolution, it is possible to make inferences about the evolutionary events that have given rise to species-specific diversification. Here we characterize the evolutionary trends found in chordate species using The Adaptive Evolution Database (TAED). TAED is a database of phylogenetically indexed gene families designed to detect episodes of directional or diversifying selection across chordates. Gene families within the database have been assessed for lineage-specific estimates of dN/dS and have been reconciled to the chordate species to identify retained duplicates. Gene families have also been mapped to the functional pathways and amino acid changes which occurred on high dN/dS lineages have been mapped to protein structures.

Results: An analysis of this exhaustive database has enabled a characterization of the processes of lineage-specific diversification in chordates. A pathway level enrichment analysis of TAED determined that pathways most commonly found to have elevated rates of evolution included those involved in metabolism, immunity, and cell signaling. An analysis of protein fold presence on proteins, after normalizing for frequency in the database, found common folds such as Rossmann folds, Jelly Roll folds, and TIM barrels were overrepresented on proteins most likely to undergo directional selection. A set of gene families which experience increased numbers of duplications within short evolutionary times are associated with pathways involved in metabolism, olfactory reception, and signaling. An analysis of protein secondary structure indicated more relaxed constraint in β-sheets and stronger constraint on alpha Helices, amidst a general preference for substitutions at exposed sites. Lastly a detailed analysis of the ornithine decarboxylase gene family, a key enzyme in the pathway for polyamine synthesis, revealed lineage-specific evolution along the lineage leading to Cetacea through rapid sequence evolution in a duplicate gene with amino acid substitutions causing active site rearrangement.

Conclusion: Episodes of lineage-specific evolution are frequent throughout chordate species. Both duplication and directional selection have played large roles in the evolution of the phylum. TAED is a powerful tool for facilitating this understanding of lineage-specific evolution.

Keywords: Comparative genomics; Gene duplication; Molecular evolution; Pathway evolution; Protein structure.

Fig. 1

Duplication analysis regression plot using family node ages as a proxy for time – The x-axis is measured in MYA based on the root node for each TAED gene family. The best Pearson’s r coefficient was found when neither axes were log transformed. The upper left half (shaded orange) of the scatterplot was used to determine TAED gene families that were statistically different from the regression line using Cook’s distance

Fig. 2

Gene tree for cetacean lineages of ornithine decarboxylase – Presented here is the gene tree taken from the TAED Tree Viewer for the TAED gene family 557. Lineages not associated with Cetaceans are collapsed. Internal nodes labeled with a while box are duplication events found within the tree. Nodes with solid grey dots represent speciation events. Nodes labeled in black indicate a leaf node. Lineages labeled in red have a dN/dS > 1 and the numbers along each branch are the associated dN/dS value for the given branch. Image was generated from the TAED Tree Viewer

Fig. 3

Pyridoxal phosphate binding site for ornithine decarboxylase along the lineage of Cetacea – A protein homology model of the ancestral protein leading to Cetacea was created. Template for the model was from human ornithine decarboxylase (PDB:2OO0; chain A). Ancestral changes occurring on the lineage for Cetacea have been mapped to the model, sites colored in red indicate nonsynonymous changes in the ancestral protein, sites colored in dark grey are synonymous site changes. The site indicated in green is the pyridoxal phosphate binding site 238. The site adjacent to the binding site is the substitution N238D found on the ancestral lineage. Image was generated from Swiss-PdbViewer

Fig. 4

Active site remodeling for ornithine decarboxylase along the lineage of Cetacea – A protein homology model of the ancestral protein leading to Cetacea was created. Template for the model was from human ornithine decarboxylase (PDB:2OO0; chain A). Ancestral changes occurring on the lineage for Cetacea have been mapped to the model, sites colored in red indicate nonsynonymous changes in the ancestral protein, sites colored in dark grey are synonymous site changes. The site indicated in gold is the active site cysteine-357. Remodeling of the active site can be seen in the changes P368Q, R375C, I376M, and R379H which are positioned around the loop containing the active site