Synonymous and single nucleotide changes facilitate the adaptation of a horizontally transferred gene

The movement of genes between microbial species, or horizontal gene transfer, is common. While this process speeds up adaptation, the functionality of horizontally transferred genes is highly constrained in the new hosts due to several reasons, and protein localization is one of them. In this study, we ask what is the minimum number of mutations that can resolve a localization problem faced by a horizontally transferred protein in a new host. Using a directed-evolution approach, we show that SNPs and a synonymous mutation can change the localization patterns of an ammonia transporter (AmtA) moved from Dictyostelium discoideum to Saccharomyces cerevisiae . Interestingly, the mutations that cause this change in localization, confer different fitness effects, are spread throughout the gene, and do not cause a uniform change in amino acids. In a novel attempt, we show how SNPs or a synonymous mutation can alter the membrane affinity of proteins, and as a result, aiding protein evolution and functional diversification.