Junk DNA plays a vital role in mammalian development

But research in the past decade has shown that some genes "dark matter" do have functions, mainly to regulate the expression of host genes — host genes account for only 2% of our genome — encoding proteins

Researchers at the University of California, Berkeley and Washington University have launched a new study to explore the function of a transposon, a component of this junk DNA

This is the first example where "junk DNA" is vital to the survival of mammals

In mice, this transposon regulates the proliferation of early fertilized embryonic cells and the timing of implantation in the mother's uterus

Senior author Lin He, professor of molecular and cell biology at the University of California, Berkeley, said these findings highlight an often overlooked evolutionary driver: viruses integrate into our genome and are repositioned as regulators of host genes.

He said: "99% of the protein-coding genes in the mouse and human genomes are the same.

Ting Wang, a professor of special medicine in the Department of Genetics at Washington University School of Medicine in St.

"The real significance of this story is that it tells us how evolution is proceeding in the most unexpected way," Wang said

This discovery may have meaning for human infertility

He said: "If 50% of our genome is non-coding or repetitive-this is dark matter-then we can easily ask the question: Can the causes of human reproduction and human infertility be explained by junk DNA sequences?"

Embryo Implantation

He is the Thomas and Stacey Siebel Distinguished Chair Professor at the University of California, Berkeley, who studies 98% or more of the human genome that does not code for proteins

In a paper published this week in the journal Cell, He and her team identified the key regulatory DNA involved: a transposon-a viral promoter-has been reused as a mouse gene The promoter of this gene produces a protein that participates in the time of cell proliferation and embryo implantation in the developing embryo

Wild mice use this transposon promoter called MT2B2 to initiate the transcription of the gene Cdk2ap1 in early embryos to produce a short protein "isoform" that increases cell proliferation in fertilized embryos and accelerates its growth.

The result of this gene knockout is that about half of the pups die at birth

Modzelewski said that the short form of the protein seems to allow the embryos implanted in mice to be regularly spaced in the uterus to prevent crowding

They found that within 24 hours of embryo implantation, the MT2B2 promoter caused the expression of the Cdk2ap1 gene to rise so sharply that the short form of the protein accounted for 95% of the two subtypes present in the embryo

The research team cooperated with Wangqing Shao, who was one of the first authors of the study and a post-doctoral researcher in Wang's research team at the University of Washington

Although transposons are usually specific to a single species--for example, the combination of humans and mice is very different--the researchers found that different species-specific families of transposons are implanting all eight mammalian species ( Opossums (including opossums) will be turned on briefly before.
Opossums are the only mammal that implants embryos into the uterus without a placenta
.

He said: "It is surprising that different species express very different transposons in preimplantation embryos, but the overall expression profile of these transposons is almost the same in all mammalian species
.
"

Colleague and co-senior author Davide Risso has developed a method to link specific transposons to preimplantation genes in order to eliminate thousands of copies of related transposons present in the genome
.
This method is essential for identifying single transposable factors with important gene regulatory activity
.

Risso said: "It is worth noting that most of the data we use is based on the previous sequencing technology, called SMART seq, which covers the complete sequence of RNA molecules
.
The current popular technology, 10x genome technology, will not show us different levels.
Protein isoforms
.
"

Viruses are evolutionary hosts

Researchers have found that in almost all eight mammalian species, there are short Cdk2ap1 and long Cdk2ap1 subtypes, but they are turned on at different times and proportions, which is earlier than the time of embryo implantation (such as mice).
) Or late (such as cows and pigs)
.
Therefore, at the protein level, both the short and long subtypes are conserved, but their expression patterns are species-specific
.

Modzelewski said: "If you have a lot of short Cdk2ap1 subtypes, such as mice, you can implant it very early, while in species such as cattle and pigs, there are no or very few short subtypes, and implantation takes up to two weeks.
Or longer
.
"

Wang suspects that the promoter that produces the long form of the protein may be the original promoter of the mouse, but the virus integrated into the genome a long time ago was later adjusted as a regulatory element, producing the short form and the opposite effect
.

"So, what happened here was a rodent-specific virus came in, and the host decided,'OK, I'm going to use you as my promoter to express this shorter Cdk2ap1 subtype
.
' We see that the system is built-in Redundancy, we can use whatever nature throws us to make it useful," Wang said
.
"Then, this new promoter happens to be stronger than the old one
.
I think this fundamentally changes the phenotype of rodents; maybe this is what makes them grow faster-the time before implantation is shorter
.
So, they may have gained some health benefits from this virus
.
"

"No matter what you observe in biology, you will see transposons being used, just because there are so many sequences," Wang added
.
"They essentially provide an evolutionary library for selection
.
"

Original search:

Andrew J.
Modzelewski, Wanqing Shao, Jingqi Chen, Angus Lee, Xin Qi, Mackenzie Noon, Kristy Tjokro, Gabriele Sales, Anne Biton, Aparna Anand, Terence P.
Speed, Zhenyu Xuan, Ting Wang, Davide Risso, Lin He.
A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development .
Cell , 2021; DOI:10.
1016/j.
cell.
2021.
09.
021