Functional constraints on replacing an essential gene with its ancient and modern homologs

Abstract

AbstractThe complexity hypothesis posits that network connectivity and protein function are two important determinants of how a gene adapts to and functions in a foreign genome. Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenoustufAgene in theEscherichia coligenome with its extant and ancestral homologs. The extant homologs representedtufvariants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrectedtufsequences dating from 0.7 to 3.6 bya. Our results demonstrate that all of the foreigntufgenes are transferable to theE. coligenome, provided that an additional copy of the EF-Tu gene,tufB, remains present in theE. coligenome. However, when thetufBgene was removed, only the variants obtained from the γ-proteobacterial family (extant and ancestral), supported growth. This demonstrates the limited functional interchangability ofE. coli tufwith its homologs. Our data show a linear correlation between relative bacterial fitness and the evolutionary distance of the extanttufhomologs inserted into theE. coligenome. Our data and analysis also suggest that the functional conservation of protein activity, and its network interactivity, act to constrain the successful transfer of this essential gene into foreign bacteria.