Scientists from the Institute for Fundamental Biomedical Research at the Biomedical Sciences Research Center ‘Alexander Fleming’ and the Smurfit Institute of Genetics at Trinity College Dublin have discovered 155 new human genes that spontaneously arose from tiny DNA sections. Some of these new ‘microgenes’ date back to the ancient origin of mammals, with a few predicted to be associated with human-specific diseases.
This graphical abstract depicts the rise of new genes in humans. Image credit: Vakirlis et al., doi: 10.1016/j.celrep.2022.111808.
“This project started back in 2017 because I was interested in novel gene evolution and figuring out how these genes originate,” said Dr. Nikolaos Vakirlis, a scientist with the Institute for Fundamental Biomedical Research at the Biomedical Sciences Research Center ‘Alexander Fleming.’
“It was put on ice for a few years, until another study got published that had some very interesting data, allowing us to get started on this work.”
Taking the previously published dataset of functionally relevant new genes, Dr. Vakirlis and his colleagues from Trinity College Dublin created an ancestral tree comparing humans to other vertebrate species.
They tracked the relationship of these genes across evolution and found 155 that popped up from regions of unique DNA.
Novel genes can arise from duplication events that already exist in the genome; however, these new genes arose from scratch.
“It was quite exciting to be working in something so new,” said Dr. Aoife McLysaght, a scientist with the Smurfit Institute of Genetics at Trinity College Dublin.
“When you start getting into these small sizes of DNA, they’re really on the edge of what is interpretable from a genome sequence, and they’re in that zone where it’s hard to know if it is biologically meaningful.”
Of these 155 new genes, 44 of them are associated with growth defects in cell cultures, demonstrating the importance of these genes in maintaining a healthy, living system.
The study authors examined patterns found within the DNA that can hint at if these genes play a role in specific diseases.
Three of these 155 genes have disease-associated DNA markers that point to connections with ailments such as muscular dystrophy, retinitis pigmentosa, and Alazami syndrome.
Apart from disease, the team also found a new gene that is associated with human heart tissue.
This gene emerged in human and chimp right after the split from gorilla and shows just how fast a gene can evolve to become essential for the body.
“It will be very interesting in future studies to understand what these microgenes might do and whether they might be directly involved in any kind of disease,” Dr. Vakirlis said.
“These genes are convenient to ignore because they’re so difficult to study, but I think it’ll be increasingly recognized that they need to be looked at and considered,” Dr. McLysaght added.
“If we’re right in what we think we have here, there’s a lot more functionally relevant stuff hidden in the human genome.”
The team’s paper was published in the journal Cell Reports.
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Nikolaos Vakirlis et al. 2022. De novo birth of functional microproteins in the human lineage. Cell Reports 41 (12): 111808; doi: 10.1016/j.celrep.2022.111808
Source : Breaking Science News