Changing an animal’s chromosome number can take millions of generations in nature during evolution – and now scientists have been able to make the same changes in lab mice in the blink of an eye.
Use of new techniques stem cells and gene editing is a major breakthrough, and one that the team hopes will reveal more about how chromosomal rearrangements can affect the way animals evolve over time.
It is on chromosomes—the strands of protein and DNA inside cells—that we find our genes, inherited from our parents and woven together to make us who we are.
For mammals like mice and us humans, chromosomes usually pair up. There are exceptions, as with sex cells.
Unfertilized embryonic stem cells are usually the best starting place for working with DNA. The lack of an extra set of chromosomes provided by the sperm cell deprives the cells of an important step in deciding which chromosomes to actively express which genes to carry out the work of building the body.
This process – called imprinting – has been a stumbling block for engineers looking to reconstruct large parts of the genome.
“Genomic imprinting is often lost, meaning information about which genes are active is lost in haploid embryonic stem cells, limiting their pluripotency and genetic engineering.” he says Biologist Li-Bin Wang from the Chinese Academy of Sciences.
“We recently discovered that by deleting three imprinted regions, we can create a stable sperm-like imprinting pattern in cells.”
Without these three naturally imprinted regions, continued fusion of chromosomes was possible. In their experiment, the researchers combined the two medium-sized 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 transferring the genetic code to the mouse offspring, although reproduction was slower than normal.
One of the combinations of 1 and 2 did not produce mouse offspring, and the other produced a slower, larger and more restless mouse offspring than the combination of chromosomes 4 and 5.
According to the researchers, the decrease in fertility is due to how the chromosomes separate after alignment, which does not happen normally. This suggests that chromosomal rearrangements are important reproductive isolation – the bulk of species that can evolve and remain separate.
“The laboratory house mouse has retained its standard 40-chromosome karyotype, or complete picture of the organism’s chromosomes, after more than 100 years of artificial breeding.” he says biologist Zhi-Kun Li, also of the Chinese Academy of Sciences.
“On longer time scales, karyotype changes caused by chromosomal rearrangements occur frequently. Rodents have 3.2-3.5 per million years and primates 1.6.”
To put this in context, rare leaps in chromosome rearrangement helped guide the evolutionary paths of our own ancestors. For example, the chromosomes that remain separate in gorillas are united in our human genome.
Such changes can occur every few hundred millennia. Although the genetic modifications made here in the laboratory are relatively small in scale, the indications are that they can have dramatic effects on the animals involved.
It’s still early days – this is a scientific study after all – but later on, it may be possible to correct misaligned or malformed chromosomes in human bloodlines. We know that chromosomal fusions and translocations in individuals can cause health problems, including childhood leukemia.
“We have demonstrated experimentally that the event of chromosomal rearrangements is a driving force in species evolution and is essential for reproductive isolation, providing a potential route for large-scale DNA engineering in mammals.” he says Lee.
The study was published Science.
