<
https://www.science.org/content/article/dark-proteome-survey-reveals-thousands-new-human-genes>
"One of the biggest surprises to emerge when the human genome was first
sequenced more than 20 years ago was how few genes it contained, less than
one-third the number some scientists had predicted. Fewer than 30,000 genes and
the proteins they encode are enough to build and operate the human body, it
seemed; recent tallies have moved even lower, to about 20,000. But a new
systematic analysis of what some call the “dark proteome” suggests scientists
have missed thousands of nontraditional genes that lurk in previously
overlooked stretches of the genome and make smaller than average proteins.
The newly described genes and their products could upend aspects of human
biology and accelerate medical discoveries. For example, one newfound gene
makes a miniature protein that appears key to a childhood cancer.
“Unless we know what the proteins in the dark proteome are and how they
contribute, our ability to [treat] diseases will be limited,” says Alan
Saghatelian, a chemical biologist at the Salk Institute for Biological Studies
who was not involved in the new research, described in a preprint posted last
month on bioRxiv.
One of the leaders of the analysis, John Prensner, began peering into the dark
proteome because so many of his searches among known genes for ones related to
cancer turned up empty-handed. “I got interested in what the rest of the genome
had to offer,” recalls Prensner, a pediatric neurooncologist now at the
University of Michigan Medical School.
He and his colleagues expanded the standard definition of a gene, typically
assumed to consist of a long protein-coding DNA sequence known as an open
reading frame (ORF), which has signals telling a cell where to start and stop
reading it. A cell transcribes the ORF sequence into messenger RNA, which
travels to cellular factories called ribosomes that assemble amino acid
sequences into proteins. A typical ORF is also preceded by a snippet of DNA
that attracts the proteins needed for the gene to be read. And for most
researchers, an ORF qualified as a gene if it encoded a protein with 100 or
more amino acids.
But biologists studying everything from yeast to snakes to humans have recently
unearthed a plethora of so-called noncanonical ORFs, which lack those prefatory
snippets and are shorter than average. Yet they are often transcribed into RNA,
and a method known as ribosomal profiling, or Ribo-Seq, has shown that many of
the transcribed RNAs attach to ribosomes, where they may be translated into
short amino acid chains—even proteins with less than a dozen animo acids.
Even then, many scientists dismissed the resulting miniproteins as unimportant,
expecting they were “noise” that were quickly degraded. It’s been very
challenging to convince people these ORFs are worth a serious look, says
Ji-Young Youn, a biochemist at the Hospital for Sick Children in Toronto.
But about 3 years ago, Prensner and colleagues demonstrated that cancer cells
contained about 550 of these microproteins. Two years earlier, Sebastiaan van
Heesch, a systems biologist at the Princess Máxima Center for Pediatric
Oncology, found similar numbers of the tiny proteins in heart tissue.
“Sebastiaan and I were finding these genes that are very, very cool and we
thought the world should know about them,” Prensner says."
Via
Fix the News:
https://fixthenews.com/279-breakneck-solarisation/
Cheers,
*** Xanni ***
--
mailto:xanni@xanadu.net Andrew Pam
http://xanadu.com.au/ Chief Scientist, Xanadu
https://glasswings.com.au/ Partner, Glass Wings
https://sericyb.com.au/ Manager, Serious Cybernetics
