A review of bacteria-animal lateral gene transfer may inform our understanding of diseases like cancer

Abstract

Lateral gene transfer (LGT) from bacteria to animals occurs more frequently than was appreciated prior to the advent of genome sequencing. In 2007, LGT from bacterial Wolbachia endosymbionts was detected in ~33% of the sequenced arthropod genomes using a bioinformatic approach. Today, Wolbachia/host LGT is thought to be widespread and many other cases of bacteria-animal LGT have been described. In insects, LGT may be more frequently associated with endosymbionts that colonize germ cells and germ stem cells, like Wolbachia endosymbionts. We speculate that LGT may occur from bacteria to a wide variety of eukaryotes, but only becomes vertically inherited when it occurs in germ cells. As such, LGT may happen routinely in somatic cells but never become inherited or fixed in the population. Lack of inheritance of such mutations greatly decreases our ability to detect them. In this review, we propose that such noninherited bacterial DNA integration into chromosomes in human somatic cells could induce mutations leading to cancer or autoimmune diseases in a manner analogous to mobile elements and viral integrations.

Figure 1. A scenario for bacteria-human LGT and carcinogenesis.

(A) Normally, human cells (red circles) can coexist with a population of microbial cells (blue rectangles), which are not drawn to scale. (B) Occasionally, bacteria-human LGT may occur from one bacterial cell to one human cell as depicted by the human chromosome with bacterial DNA within it (pink chromosome with blue insertion). The bacterial sequence (blue) inserted into the human sequence (red) is illustrated below. (C) The cell with the LGT can undergo transformation to a cancerous phenotype, represented by the scalloped red cell. Such transformation may be related to the integrations or may instead be related to some other alteration in the cell. (D) The now cancerous cell clonally expands and forms a tumor where the majority of cancer cells share the original LGT.