Microbes - part of our DNA

30 May 2019

Microbes - part of our DNA

Microbes can be linked to every part of our existence. They use our bodies as their homes, assist in providing our crops with nutrients and even help to degrade our waste. It is therefore no surprise that microbes outnumber human cells in our bodies by 1:1 with more than 10,000 bacterial species found in humans [1, 2]. We all provide a habitat for trillions of microbes, but we have also altered the world around us to drive the evolution of new microbes. Newly evolved microbes include Ideonella sakaiensis that feeds on the plastic PET (polyethylene terephthalate) we created and use in plastic bottles [3].

 

There is no denying that microbes are interconnected with us in our modern world, and the sheer abundance of microbes in the human body indicates that this connection is ancient. So ancient that microbes even appear to shape our DNA. A few weeks ago, I found an article highlighting the presence of viral DNA in the human genome! This was a concept I had never come across before, and since it has consumed my mind. I had to know more. What if microbes are responsible for making us human?

 

 

Firstly, how does microbial DNA get combined with ours? There is evidence of bacterial genes being included into our DNA through horizontal gene transfer (HGT) and through the inclusion of transposable elements [4, 5]. HGT is the transfer of genetic material from one organism to an often-unrelated organism, unlike vertical gene transfer where genetic material passes from parent to child. Transposable elements are genes that can move or jump from one part of the DNA code to another, possibly causing mutations depending on which area of DNA the transposable element jumps into. Viral DNA can combine with ours through injection of the DNA into our cells or through incorporation of transposable elements [6].

 

 

The transfer of genes from microbes to humans has been identified by comparing the human genomic code to that of microbes. From this comparison, there is evidence that dozens of transposable elements have been included into human DNA [5]. However, evidence of HGT from bacteria to humans and other vertebrates is observed even more widely with estimates of between 41 and 223 proteins found in humans that originate from a bacterial source [4, 5]. In addition to bacterial genes, viral genes including the human endogenous retroviruses are estimated to comprise 1% of the human genome [6]. Retroviruses inject their RNA into a host cell for replication. As viruses cannot self-replicate, they are reliant on the host cell for reproduction, but what if we could ‘tame’ a virus and include useful genes from it?

 

One of the ‘tame’ viral genes found in humans makes the protein syncytin. This protein causes cells to join in the placenta and prevents the mother’s immune system from attacking the developing foetus [7, 8]. This retrovirus has been ‘tamed’ by our body and integrated to aid the development of our next generation. It is unknown when this virus became part of our DNA, but it is also found in apes and old-world monkeys including baboons and macaques [8]. The benefits of retroviruses in placental development have also been observed in other mammalian species including mice, but these genetic codes differ from the inclusion of different retroviruses.

 

 

While microbes can incorporate their DNA into ours resulting in beneficial outcomes, there is also the possibility for the transfer of genes to cause damage to the cell. The presence of viral DNA in the human genome has been linked to cancer and is estimated to cause 10-15% of cancers [9]. These cancerous tumours can be caused by infection with 7 different viruses including hepatitis B and C viruses, human herpes virus and the human papillomavirus [9]. In addition, bacterial DNA inserted into human cells has also been linked to cancer. When cancerous and healthy human cells were tested for bacterial HGT, evidence of HGT was found in 99.9% of the cancerous cells and only around 20% of healthy cells [10].  The bacterial genes inserted were from Acinetobacter (potentially resulting in HGT post infection with the disease-causing Acinetobacter baumannii) and Pseudomonas [10]. These cancers are usually the result of microbial infections which will only affect the individual’s DNA and not pass down to future generations like our ‘tamed’ microbial DNA that has become fully incorporated into the human genome.

 

I find it intriguing but scary that microbes could be altering my DNA. With the transfer of microbial DNA having the potential to cause cancer, I am surprised that the body doesn’t offer more of an immune response to prevent gene transfer. I can’t help but wonder if the microbial DNA now incorporated in the human genome is from once pathogenic or cancer-causing microbes that our body has tamed? I also wonder if the body tolerates the transfer of microbial genes hoping to optimise useful DNA, such as the syncytin protein. The evolution of humans and microbes are both complex, but I would have never thought that microbes would literally shape our DNA.  

 

Further reading

[1] Sender R., Fuchs S., Milo R. (2016). Revised estimated for the number of human and bacteria cells in the body. PLoS Biology, 14: e1002533.

 

[2] National Institute of Health (2012) NIH human microbiome project defines normal bacterial makeup of the body [Online]. Available from: https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body

 

[3] Yoshida S., Hiraga K., Takehana T., Taniguchi I., Yamaji H., Maeda Y., Toyohara K., Miyamoto K., Kimura Y., Oda K. (2016). A bacterium that degrade and assimilates poly (ethylene terephthalate). Science, 351:1196-1199 

 

[4] Salzberg S.L., White O., Peterson J., Eisen J.A. (2001) Microbial genes in the human genome: lateral transfer or gene loss? Science, 292: 1903-1906

 

[5] International Human Genome Sequencing Consortium (2001). Initial sequencing and analysis of the human genome. Nature, 407: 860-921

 

[6] Löwer R., Löwer J., Kurth R. (1996). The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proceedings of the National Academy of Sciences of the United States of America, 93: 5177-5184

 

[7] Arney K. (2019) The viruses that made us human in BBC Focus magazine collection Vol 5 The ultimate guide to your genes, Immediate Media.

 

[8] Unknown (2019). Syncytin-1 [Online]. Available from: https://en.wikipedia.org/wiki/Syncytin-1

 

[9] Moore P.S., Chang Y. (2010). Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nature Reviews Cancer, 10: 878-889

 

[10] Riley D.R., Sieber K.B., Robinson K.M., White J.R., Ganesan A., Nourbakhsh S., Hotopp J.C.D. (2013). Bacteria-human somatic cell lateral gene transfer is enriched in cancer cells. PLOS Computational Biology, 9: e1003107