The complexity hypothesis and other connectivity barriers to lateral gene transfer

With an exponential increase in the number of available genomes and more accurate evolutionary methods it became evident that lateral gene transfer (LGT) plays a pivotal role in explaining the vast variability in gene content among microbial species. While all genes are probably susceptible to LGT, the tendency to undergo LGT is highly variable among genes. Over a decade ago, it was suggested that the function of a gene largely determines its transferability as Informational (those involved in transcription, translation, and related processes) genes were found to be less transferable than Operational genes (those involved in other housekeeping functions). Later, it was additionally shown that the complexity of genes (involvement in complex structures) is an important factor in determining transferability. Since it was first suggested, this co called complexity hypothesis became the center of discussion regarding gene transferability. In this chapter we will discuss the development of that hypothesis in the literature including the ample support for its general observations as well as the reservations that were made regarding some of its predictions. Finally, we conclude that at least for lateral transfer of novel gene families that requires integration of new components into the cellular network, genes with high connectivity (i.e., complexity) are significantly less likely to undergo LGT. However, we suggest that the initial distinctions into two functional categories (i.e., Informational vs. Operational genes) may have been somewhat misleading because both highly transferred Informational and lowly transferred Operational genes exist, and thus we suggest the mechanistic distinction between highly connected core genes and the lowly connected peripheral genes.