Changing the number of chromosomes an animal has can take millions of generations to happen in nature over the course of evolution, and now scientists have been able to make those same changes in lab mice in the blink of an eye. eyes
The new technique, which uses stem cells and gene editing, is a major breakthrough, and one that the team hopes will reveal more about how chromosome rearrangements can influence the way animals evolve over time.
It is in the chromosomes, those strands of protein and DNA inside cells, that we find our genes, inherited from our parents and mixed together to make us who we are.
For mammals like mice and us humans, chromosomes usually come paired. There are exceptions, such as in sex cells.
Unfertilized embryonic stem cells are usually the best place to start for DNA tweaking. The lack of this extra set of chromosomes provided by a sperm cell, however, deprives the cells of an important step in negotiating which genes on which chromosomes will be marked as active to do the job. to build a body
This process, called imprinting, was a stumbling block for engineers interested in restructuring large chunks of the genome.
“Genomic imprinting is frequently lost, meaning information about which genes should be active disappears in haploid embryonic stem cells, limiting their pluripotency and genetic engineering,” says biologist LiBin Wang of the Chinese Academy of Sciences.
“We recently discovered that by deleting three imprinted regions, we could establish a stable spermlike imprinting pattern in cells.”
Without these three naturally imprinted regions, lasting chromosome fusion was possible. In their experiments, the researchers fused two mediumsized chromosomes (4 and 5) and the two largest chromosomes (1 and 2) in two different orientations, resulting in three different arrangements.
The fusion of chromosomes 4 and 5 was the most successful in passing on the genetic code to the mice’s offspring, although reproduction was slower than normal.
One of the fusions 1 and 2 produced no offspring of mice, while the other produced offspring of mice that were slower, larger and more restless than those from the fusion of chromosomes 4 and 5.
According to the researchers, the drops in fertility are due to how the chromosomes separate after alignment, which does not happen in the normal way. It shows that chromosomal rearrangement is crucial for reproductive isolation, a key part of allowing species to evolve and stay apart.
“The laboratory house mouse has maintained a standard karyotype of 40 chromosomes, or the complete picture of an organism’s chromosomes, after more than 100 years of artificial breeding,” says biologist ZhiKun Li, also of the ‘Chinese Academy of Sciences.
“On longer time scales, however, karyotype changes caused by chromosomal rearrangements are common. Rodents have 3.2 to 3.5 rearrangements per million years, while primates have 1.6.”
To put this into context, rare jumps in chromosomal rearrangement helped direct the evolutionary paths of our own ancestors. Chromosomes that remain separate in gorillas, for example, are fused into one in our human genome.
These kinds of changes can happen once every few hundred millennia. Although the genetic edits made here in the lab were on a relatively small scale, the signs are that they could have some dramatic effects on the animals involved.
It’s still early days, this is early science after all, but down the line, there might be a chance to correct misaligned or malformed chromosomes in human bloodlines. We know that in individuals, chromosomal fusions and rearrangements can lead to health problems, including childhood leukemia.
“We have shown experimentally that the chromosomal rearrangement event is the driving force behind species evolution and important for reproductive isolation, providing a potential route for largescale DNA engineering in mammals” , says Li.
The research was published in science.