Humans are still evolving! The power comes from microgenes in the genome

According to a study published Dec.
20 in Cell Reports, humans are still evolving new genes
.
Researchers report that as our lineage evolved, at least 155 human genes emerged from regions of DNA that were previously considered "junk," including two human-specific genes
isolated from chimpanzees about 4 million to 6 million years ago.

"I think it's a great study," said Alan Saghatelian, a biologist at the Salk Institute who was not involved in the work
.
He added that he would "not be surprised"
if more of these genes were hidden in obvious places.

The genes described in the new study remained undetected for a long time because they were small: they were only 300 nucleotides at most long, while a typical human gene averaged 10 to 15,000 base pairs
.
Saghatelian explains that although they possess start and stop codons that can be read by a cell's transcriptional machinery like traditional genes, these so-called microgenes — sometimes called short open reading frameworks (sORFs) — have long been considered functionless
.

But recent studies have found that knocking out sORFs hinders cell growth, suggesting that they are important
after all.
For example, a 2020 study found hundreds of functional sORFs in human cells, both in coding and noncoding regions
of the genome.
Nikolaos Vakirlis, a computational evolutionary biologist at the Alexander Fleming Center for Biomedical Sciences Research in Vari, Greece, was intrigued by the number, and he and his colleagues felt compelled to further study these genetic strange phenomena and launched the newly published study
.
Vakirlis said: "We find genes for specific species everywhere
.
So there must be an evolutionary route
to their origin.

Using data from the 2020 study, the team scanned the genomes of humans and vertebrates for functional sORFs that produce proteins
.
Then, using known human and vertebrate phylogenetic information, they predicted the evolutionary relationship
between sORFs estimated as new microgenes emerged in evolutionary history.

Through this process, the team identified 155 microgenes
common to all vertebrates.
According to data from previous studies, 44 of them are essential
for cell growth.
Three of them have disease markers associated with diseases such as muscular dystrophy, retinitis pigmentosa, and Alazami syndrome
.
The team also discovered a microgene associated with human heart tissue that popped up
after chimpanzees and humans separated from gorillas about 7 million to 9 million years ago.

Interestingly, Vakirlis and his colleagues found that these new genes were created from noncoding regions of DNA, rather than by mutating or copying existing genes
.
While gene duplication is thought to be the primary source of new genes in all species, the emergence of microgenes may explain how humans developed some unique human traits, as well as how other animals acquired unique species-specific phenotypes
.

John Prensner, a doctor at Dana Farber Cancer Institute and a postdoctoral fellow at the Broad Institute who was not involved in the study, said in an email: "This study is really important
.
" He explained that scientists have known about sORFs and other non-canonical open reading frameworks for some time, but have not yet determined what they might do
.
Even today, he explains, microgenes are a potential evolutionary pathway
.
They encode "primitive proteins," or small proteins
that organisms begin to try.
These proteins may go nowhere, disappearing from the genome over time, but they may also have useful functions that eventually anchor
in the genome.

Vakirlis said that "there may be more" sORFs waiting to be discovered, and perhaps more sORFs are associated with
the disease.
"These are just experiments
on two cell lines," he notes.
As more experiments are done on other cell lines, researchers may find a wealth of health-related information "and start thinking about whether we can target [sORFs] for therapeutic purposes
.
" ”