We may have split from our primate cousins millions of years ago, but a new study shows how humans are evolving in ways we never imagined.
Researchers at Biomedical Sciences Research Center Alexander Fleming (BSRC Flemming) in Greece and Trinity College Dublin, Ireland have identified 155 genes in our genome that arose from small, non-coding stretches of DNA. Many appear to play crucial roles in our biology, showing how entirely new genes can rapidly evolve to become essential.
New genes typically arise through well-known mechanisms such as dual eventswhere our genetic machinery inadvertently produces copies of pre-existing genes that may be appropriate for new functions over time.
But the 155 microgenes identified in this study appear to have arisen from scratch, in stretches of DNA did not contain any instructions which our body uses to build molecules.
Since the proteins meant to encode these new genes would be incredibly tiny, these DNA sequences are hard to find and difficult to study and are therefore often overlooked in research.
“This project started in 2017 because I was interested in the evolution of novel genes and how these genes come about,” says evolutionary geneticist Nikolaos Vakirlisby BSRC Flemming in Greece.
“It was put on hold for a couple of years until another study came out that contained some very interesting data that allowed us to start this work.”
That other studypublished in 2020 by a team of researchers from the University of California, San Francisco cataloged a stack of microproteins produced by non-coding regions once referred to as “junk DNA”..
The team behind this new study then created a genetic ancestry tree to compare these tiny sequences found in our genomes to those in 99 other vertebrate species and to track the evolution of the genes over time.
Some of the new “microgenes” identified in this new study can be traced back to the earliest days of mammals, while others are more recent. Two of the genes identified in the study appear to have arisen since humans and chimpanzees separated, the researchers found.
“We sought to identify and study instances in the human lineage of small proteins that evolved from previously non-coding sequences and acquired function either immediately or shortly thereafter,” the team writes their published work.
“This is doubly important: for our understanding of the fascinating and still largely mysterious phenomenon of the de novo birth of genes, but also for our understanding of the full functional potential of the human genome.”
It is already known that microproteins have a variety of functions, from helping regulate the expression of other genes to associating with larger proteins, including our cell membranes. However, while some microproteins perform vital biological tasks, others are simply useless.
“When you start looking at these small sizes of DNA, they’re really on the edge of what’s interpretable from a genome sequence, and they’re in an area where it’s hard to know if it’s biologically meaningful is.” explained Geneticist Aoife McLysaght from Trinity College Dublin.
A gene involved in building our heart tissues arose when an ancestor common to humans and chimpanzees diverged from the gorilla’s ancestor. If this microgene did indeed emerge in the last few million years, it’s compelling evidence that these evolving parts of our DNA can quickly become essential to the body.
The researchers then studied the functions of the sequences by deleting genes one by one in cells grown in the lab. Forty-four of the cell cultures showed growth defects, confirming that these now-missing stretches of DNA play a critical role in keeping us functioning.
In other comparative analyses, the researchers also identified known disease-associated variants in three of the new genes. The presence of these random mutations at a single base position in DNA could suggest an association with muscular dystrophy, retinitis pigmentosa and Alazami syndrome, but further research will be needed to clarify these relationships.
In the face of modern technology and medicine, it can be a challenge to assess the magnitude of the biological changes humans have undergone as a species through natural selection. But our fitness was heavily embossed through pressures the diet and illness over the millennia and will no doubt continue to adapt even in a technologically advanced world.
Exactly how the spontaneous emergence of new genes within the noncoding region occurs is not yet clear, but with our newfound ability to track these genes, we may be closer to the discovery.
“If we’re right about what we think we have here, there’s a lot more functionally relevant stuff hidden in the human genome,” says McLysaght.
The research was published in cell reports.