20 Apr We Are Able to See Thanks to a Protein Acquired from Bacteria
MedicalResearch.com Interview with:
a Selma and Robert Silagi Award for Undergraduate Excellence winner
UC San Diego and now a graduate student at MIT
Matt Daugherty Ph.D
University of California, San Diego
Department of Molecular Biology, School of Biological Sciences
La Jolla CA, 92093-0377
MedicalResearch.com: What is the background for this study? Would you explain the role of retinoid-binding protein?
Response: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery.
IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases.
MedicalResearch.com: How might this protein have a distant bacterial heritage?
Response: We initially used protein sequence similarity to identify which species encode a protein similar to IRBP. We observed that IRBP was encoded by most vertebrates but was absent in a majority of non-vertebrate animals, as has been seen before. But we also saw that the bacteria contain proteins that appeared surprisingly similar to vertebrate IRBP. This hinted that IRBP may not have been inherited from a common ancestor of vertebrate and invertebrate animals, but may have been directly acquired by an ancestral vertebrate by taking up a bacterial gene and integrating it into its genome. This type of bacteria-to-animal HGT is extremely rare, so we wanted to make sure we did everything we could to confirm this was true. To do this, we extensively gathered sequences across available genome sequences of eukaryotes (vertebrates and invertebrates, as well as single-cell eukaryotes) and bacteria. From there, we built phylogenetic trees using a variety of maximum likelihood reconstruction methods that allow us to determine the relatedness of each protein sequence to each other. All of these sequences and computational methods allowed us to infer that vertebrate IRBP is in fact most closely related to bacterial proteins than any other eukaryotic protein, which is the key piece of evidence that this was acquired by HGT.
What is interesting is that after the gene transfer, vertebrates appeared to have evolved features of IRBP such as duplicated domains, loss of an ancestral bacterial enzymatic activity, and the ability to secrete the protein into the space between photoreceptor and RPE cells. This indicates that after acquisition of the bacterial gene, several changes were made to IRBP to integrate it fully into the vertebrate visual cycle.
MedicalResearch.com: What should readers take away from your report? Could other genes have been acquired in a similar fashion?
Response: Our discovery of the bacterial origin for vertebrate IRBP struck us because the evolution of the vertebrate eye has been intriguing and mysterious, with several gaps in knowledge yet to be filled. This study says that at least one of those evolutionary innovations occurred not by “tinkering” with genes that already existed in that organism, but by acquiring an entirely new gene from bacteria.
We are excited by the immense possibility of discovering additional exciting examples of genes and functions in animals as well as plants and fungi that owe their origins to bacteria. The story of IRBP is a striking illustration of the underappreciated influence of bacteria on vertebrate evolution, and with high quality genome sequencing data becoming increasingly available, we are excited to probe those datasets using our methods to investigate further examples of HGT between bacteria and other forms of life.
Bacterial origin of a key innovation in the evolution of the vertebrate eye” by Chinmay A. Kalluraya, Alexander J. Weitzel, Brian V. Tsu and Matthew D. Daugherty, doi:10.1073/pnas.2214815120, PNAS, 10 Apr 2023.
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