Genomics research generates vast amounts of sequence data for thousands of genes. Some companies use this sequence data to try to predict the function of each gene and its potential to impact key traits. Others try to match the thousands of random deoxyribonucleic acid (“DNA”) changes between individuals with differences in traits. Evolutionary Genomics’ approach is to first narrow the search to genes that have undergone adaptive evolution (positively selected genes) in an organism that has an adapted trait of potential commercial value. Evolutionary Genomics then focuses functional genomics efforts on demonstrating the effects of these genes on the desired traits.
Evolutionary Genomics uses the Adapted Traits Platform to perform high throughput molecular evolution analysis to identify positively selected genes based on Ka/Ks analysis (as defined below). Ka/Ks analysis was developed to document the role of positive selection on known protein coding genes. Molecular-level adaptive evolution is indicated when comparisons of homologous protein coding sequences from closely related species show that the number of amino acid differences fixed due to selection exceeds what can be expected by neutral evolution. Molecular-level positive selection can be detected in protein-coding genes by pairwise comparisons of the ratios of non-synonymous nucleotide substitutions per non-synonymous site (Ka) to synonymous substitutions per synonymous site (Ks). The algorithm, by comparing substitutions per site, takes into account, in rigorous fashion, the effect of bias and degeneracy in the genetic code, and also compensates for the effects of multiple hits at the same site. Ka/Ks ratios significantly greater than unity strongly suggest that positive selection has fixed greater numbers of amino acid replacements than can be expected as a result of chance alone.
Dr. Walter Messier, a Company founder and our Chief Technology Officer, published a seminal paper in the field: Messier and Stewart (1997) “Episodic adaptive evolution of primate lysozymes” Nature 385:151-154. The work described in this publication demonstrated that a known lysozyme gene that had been recruited for a new function to aid in digestion of leaves as a food source in certain monkeys had the kind of adaptive genetic changes indicating that the lysozyme gene had evolved more rapidly than the neutral substitution rate, indicating Darwinian positive selection. Many groups have used such methods to document Darwinian positive selection in other proteins. It was Dr. Messier’s insight that genes controlling a trait of interest could be identified by using molecular evolution analysis as a screen, comparing genes in a species with a trait to genes of a closely related species lacking the trait. The adapted genes found in such a screen could then be validated to determine their role in the presence or absence of the trait of interest.