Two Major Paths of Gene-Duplicates Evolution

Abstract

Evolving genomes increase a number of their genes by gene duplications. To escape degradation in a functionless pseudogene, any gene duplicate needs to be guarded by negative (purifying) selection from otherwise inevitable fixation of degenerative mutations. In the present study we focus on the evolutionary stage at which new duplicates come under such surveillance. Our analyses of several genomes indicate that in about 10% gene pairs, selection begins to guard a new gene copy very soon after a duplication event whereas the vast majority (90%) of extra genes remain redundant and unrecognised by selection. Such duplicates accumulate all mutations (including degenerative) in neutral fashion and are actually destined to become pseudogenes. We revealed this "two-stream" evolutionary pattern by the analysis of mutations in 2nd versus 3rd codon positions but not by the routinely used ratio of amino acid replacements (R) versus silent substitutions (S), i.e. the '2nd vs. 3rd' metric proved to be more resolving than the traditional 'R vs. S' one for distinguishing neutrally evolving future pseudogenes from their functional counterparts controlled by negative selection. In gene databases for large genomes, hundreds of future pseudogenes are annotated as functional genes because they do look like intact and valuable by standard criteria, including even active transcription and translation. Apparently, these "pseudogenes-to-be" over-cloud and mimic those very infrequent gene duplicates with increased sequence evolution rates driven by positive selection.