Small new genes in human DNA show how we are still evolving

We may have parted ways with our primate cousins ​​millions of years ago, but a new study shows how humans continue to evolve in ways we never imagined.

Researchers from the Alexander Fleming Biomedical Sciences Research Center (BSRC Flemming) in Greece and Trinity College Dublin, Ireland, have identified 155 genes in our genome that emerged from small, non-coding sections of DNA. Many of them seem to play a crucial role in our biology, revealing how completely new genes can quickly evolve to become essential.

New genes usually emerge through well-known mechanisms such as duplication events, whereby our genetic machinery mistakenly produces copies of pre-existing genes that can end up fitting new functions over time.

But the 155 microgens identified in this study appear to have emerged from scratch, in stretches of DNA that previously did not contain the instructions our bodies use to build molecules.

Because the proteins thought to be encoded by these new genes would be so small, these DNA sequences are hard to find and difficult to study, and thus are often overlooked in research.

“I started this project in 2017 because I was interested in the evolution of new genes and to discover how these genes arise,” says evolutionary geneticist Nikolaos Vakirelis, from BSRC Flemming in Greece.

“It was put on ice for a few years, until another study was published with some very interesting data, which allowed us to get started on this work.”

That other study, published in 2020 by a team of researchers at the University of California San Francisco, cataloged a mound of tiny proteins produced by non-coding regions once described as “junk DNA.”

The team behind this new study subsequently created a genetic ancestry tree to compare those exact sequences found in our genomes with those of 99 other vertebrate species, tracing the evolution of genes over time.

Some of the new “micromolecules” identified in this new study can be traced back to the earliest days of mammals, while others are more recent additions. The researchers found that two of the genes identified in the study appeared since the split between humans and chimpanzees.

“We sought to identify and examine cases in the human lineage of small proteins that have evolved from previously non-coding sequences and acquired functions either immediately or shortly thereafter,” the team wrote in their published paper.

“This is doubly important: for our understanding of the intriguing, still largely obscure phenomenon of de novo gene birth, but also for our appreciation of the full functional potential of the human genome.”

Microproteins are already known to have a variety of functions from helping to regulate the expressions of other genes to joining forces with larger proteins including our cell membranes. However, while some microproteins perform vital biological tasks, others are useless.

“When you start to get into these small volumes of DNA, they’re really on the edge of what can be interpreted from the genome sequence, and they’re in that area where it’s hard to know if it’s biologically meaningful,” explains Trinity College Dublin geneticist Aoife McLysaght.

A gene involved in building heart tissue emerged when a common ancestor of humans and chimpanzees diverged from the ancestors of gorillas. If this microgen gene has indeed appeared in the last few million years, it is striking evidence that these evolving parts of our DNA can quickly become essential to the body.

The researchers then probed the functions of the sequence by deleting genes, one by one, in cells grown in the lab. Forty-four cell cultures continued to show growth defects, confirming that those now-missing pieces of DNA play important roles in keeping us functioning.

In other comparative analyses, the researchers also identified variants known to be associated with the disease in three of the new genes. The presence of these mutations chanced upon at a single base locus in DNA may indicate an association between muscular dystrophy, retinitis pigmentosa, and Alazami syndrome, but further research will be required to clarify these relationships.

In light of modern technology and medicine, estimating the amount of biological change humans have experienced as a species at the hands of natural selection can be challenging. But our physical fitness has been shaped largely by the stresses of diet and disease over thousands of years, and will undoubtedly continue to adapt even in a technologically advanced world.

It is not yet clear how the spontaneous creation of new genes within the non-coding region occurs, but with our newfound ability to track these genes, we may be closer to finding out.

“If we’re right in what we think we have here, there are a lot of functionally related things hidden away in the human genome,” He says maclesagt.

Research published in Cell Reports.

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