If We Don’t, the Microbes Will
While high-minded researchers earnestly debate the necessity for caution on editing the human germ line, it appears that everyday bacteria and fungi have done so for millions of years–perhaps ever since the evolution of multicellular life.
We are talking about horizontal gene transfer (HGT), that is, the “illegitimate” transfer of DNA from one organism to another, without vertical (parental) inheritance. Shades of Bleak House come to mind. For decades, HGT via bacteriophages and plasmids was relegated to microbes. Surprisingly, the emerging recognition of viral sequences throughout the human genome has done little to alter this non-recognition of bacterial genes. Part of the reason is that until recently, genome sequencing required a step of amplification that involved cloning within bacteria. It was hard to avoid contaminating bits of bacterial DNA; so researchers excluded any bacterial sequences they found, as likely contaminants.
Today’s third-generation sequencers such as Illumina are orders of magnitude more sensitive and may sequence DNA fragments that have never seen a bacterial vector. Nevertheless, bacterial and even fungal genes emerge.
The figure above represents some of the “non-metazoan” sequences found in a human genome. Authors Alastair Crisp, Chiara Boschetti and colleagues identified genes of microbial origin based on their bitscore, that is, how many of the base pairs line up. Class C genes (red) show overall better alignment with microbial genes (threshold score 30) and best match with a particular microbial gene (score 100). Class B genes (blue) show scores of >30 for all orthologs of the gene in other species; orthologs meaning “the same” gene due to shared ancestry. Class A genes (gold) are a subset of class B genes with even poorer homology to genes of metazoan (multicellular) organisms. In contrast, all other garden-variety human genes are shown as gray. But the take-home is that red, blue, and gold genes abound.
What are some of these genes, and what do they do? Most do surprisingly fundamental cell tasks.
- ABO blood type. The histo-blood group transferase gene (transferase A or transferase B) encodes variant forms of an enzyme that make the A or B antigens on the surface of blood cells, defining blood of type A or B. This gene appears to derive from bacteria.
- Hyaluronan synthase. A gene of fungal origin encodes an enzyme that makes hyaluronan, a sugar polymer found throughout our cell membranes. An adult human body typically contains 15 grams of hyaluronan.
Other human genes of suspect origin encode enzymes of amino-acid synthesis, the innate immune system, and anti-oxidant defense.
So how do all these bacterial and fungal genes get into the monumentally protected human germ line? One commenter helpfully points out that sperm delivery offers a convenient means of “natural” insertion of foreign DNA into an egg. In the laboratory, sperm-adherent DNA delivery has been demonstrated in mice. An alternative source, the human placenta abounds with bacteria–hence the placental microbiome project.
Meanwhile, in other news researchers report that “Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity.” That is, digestive bacteria can be engineered to produce “potent anorexigenic lipids”. Apparently, the potential editing of our microbiome does not yet raise the same alarms as editing of “our own” cells. Perhaps it should.