The Chinese Academy of Sciences (CAS) claims to have discovered a revolutionary approach for programmable chromosomal fusion in the laboratory, successfully producing mice with genetic mutations “that occur on a million-year evolutionary scale.”
According to Phys.org, the discoveries could offer insight into how chromosome rearrangements—the neat bundles of structured genes delivered in equal numbers by each parent, which align and trade or combine features to make offspring—influence evolution.
“After more than 100 years of artificial breeding, the laboratory house mouse has preserved a standard 40-chromosome karyotype—or the complete picture of an organism’s chromosomes,” said Li Zhikun, a researcher at CAS’s Institute of Zoology.
“However, karyotype alterations produced by chromosome rearrangements are prevalent over longer time scales. Rodents have 3.2 to 3.5 rearrangements every million years, while primates experience 1.6 “Li, the study’s co-first author, remarked.
According to the South China Morning Post, the mouse, known as Xiao Zhu, or “Little Bamboo,” was the world’s first mammal with totally reprogrammed genes.
By demonstrating that chromosome-level engineering is possible in mammals and successfully producing a laboratory house mouse with a novel and sustainable karyotype, the study claims to have gained crucial insight into how chromosomal rearrangements may affect evolution.
Small modifications, according to Li, can have a tremendous impact. In primates, humans and gorillas differ by 1.6 alterations. Gorillas have two separate chromosomes, whereas humans have two fused chromosomes, and gorillas have two unique chromosomes as a result of a translocation between ancestor human chromosomes.
Fusions and translocations can result in missing or additional chromosomes, as well as disorders such as pediatric leukemia.
While the consistent reliability of the chromosomes is beneficial for understanding how things work on a short time scale, Li believes that the ability to create alterations could enrich genetic understanding spanning millennia, such as how to rectify misaligned or faulty chromosomes.
Although attempts to adapt the technology to mammals have failed, other researchers have successfully altered yeast chromosomes.
Imprinting on the genome
“In haploid embryonic stem cells, genomic imprinting is frequently lost, meaning the information about which genes should be active disappears, limiting their pluripotency and genetic engineering,” said Wang Libin, first author of the study and a researcher at CAS and the Beijing Institute for Stem Cell and Regenerative Medicine.
“By eliminating three imprinted sites, we were able to produce a stable sperm-like imprinting pattern in the cells.”
In diploid cells, two sets of chromosomes align and negotiate the genetics of the final creature. This is referred to as genomic imprinting, and it happens when a dominant gene is marked active while a recessive gene is marked inactive.
The scientific manipulation of the process is possible, but earlier attempts in mammalian cells have failed to stick to the information.
Wang notes that the procedure requires stem cells to be derived from unfertilized mouse embryos, which means the cells contain only one set of chromosomes.
The emergence of a new species is an evolutionary indication.
According to CGTN, a Chinese state-run English-language news channel based in Beijing, scientists genetically produced a type of mouse with 19 chromosomal pairs, one pair less than is typical in this species, and a portion of these genetic modifications can be handed down to offspring.
“The initial forms and differentiation of stem cells were hardly altered; however, karyotypes with merged 1 and 2 chromosomes resulted in stopped development,” Wang explained.
“The smaller fused chromosome, made up of chromosomes 4 and 5, was successfully passed on to progeny.”
According to Wang, the researchers revealed that the decreased fertility was caused by an anomaly in how chromosomes divided after alignment.
According to him, this discovery demonstrated the importance of chromosomal rearrangement in establishing reproductive isolation, a critical evolutionary signal of the development of a new species.
The findings were first published in Nature.