A team of international scientists have succeeded in creating a new version of the common brewers’ yeast, where a “designer” chromosome makes its debut: Led by Jef Boeke, PhD, the director of the Institute for Systems Genetics at NYU Langone Medical Center, the team has engineered the first functional chromosome in yeast that presents great prospects for the field of synthetic biology and future scientific discoveries. The study, which was published in the journal Science on March 27, is the biggest step so far in an international project to fabricate the entire genome of synthetic yeast.
Taking tiny pieces of artificial DNA from brewer’s yeast (Saccharomyces cerevisiae), the researchers fused them into a synthetic type of chromosome – a process that is being considered a feat of bioengineering, which works to produce microbes that can spur new medicines, biofuels and raw materials for food. The research has also advanced the creation of synthetic flora and fauna.
In the last five years, artificial chromosomes have already been constructed. However, they were fairly loyal copies of naturally occurring chromosomes, which resemble minute thread-like formations packed tightly with DNA operating as the body’s genetic makeup. This research effort, led by Dr. Boeke , is the first time an eukaryotic chromosome has been built entirely from scratch.
It is also the first major advancement in terms of yeast genetics after 1996, when researchers came up with the complete DNA code of the organism. According to Dr. Boeke, who recently moved over to NYU Langone from John Hopkins University, the research has shifted focus from theory to reality in the field of synthetic biology.
The making of the designer chromosome involved a software modification of yeast chromosome III, titled “synIII”, which was combined with brewer’s yeast. Being the smallest among yeast’s 16 chromosomes, it manages how the cells engage in mating and undergo changes genetically, thereby making it an ideal choice for the research.
While bringing forward the most comprehensively revamped chromosome till date, the research is being hailed for achieving its (the designer chromosome’s) incorporation into a live yeast cell. The yeast carrying the new, deliberately adjusted chromosome behave in the same way normal yeast does. Though they behave like wild yeast, the designer chromosome has endowed them with new capacities, which enable them to do what wild yeast cannot.
The seven-year long effort has created a shorter chromosome, with 273,871 base pairs of DNA, when compared to its original yeast complement which contains 316,667 base pairs. Dr. Boeke’s team carried out over 500 alterations to the genetic base of synIII, where they discarded repetitive sections in approximately 47,841 DNA base pairs. These removals were made because they were seen as unnecessary to the reproduction and growth of a chromosome.
The team also took out what is popularly known as “junk DNA”, which contained base pairs that were proven to have no encoding for any specific proteins. Also among the junk DNA were “jumping gene” segments which are known for random movement and introduction of mutations. The researchers either added or modified different sets of base pairs that made it possible for them to tag DNA as native or synthetic. In this way, they were also able to erase or shift genes on synIII, the debut designer chromosome.
By scrambling the genetic blueprint of synIII in this way, researchers have generated a new type of yeast that possess an enormous variety in its genetic makeup. The genetic variety allows scientists to isolate particular strains that grow ideally or most rapidly or attain a certain ability.
For Dr. Boeke, who calls this evolution on hyperspeed, this aspect represented where the real strength of synthetic biology will play out in the future. Reactions coming in from researchers not involved in the study, have pegged it as an important chromosome redesign that has made it possible to further understand and engineer it. Much of the work towards integrating short DNA pieces into lengthier segments was carried out by undergraduate students at the John Hopkins University as part of a class project. A few of these former students also co-authored the study.
Though yeast and human beings do not resemble each other in any way, their deepest biological roots are similar and fall under the same category. They are both organisms that deposit their chromosomes in their nuclei, unlike other organisms. The only synthetic DNA that existed until now were tailor-made for viruses and bacteria, which do not fall under the same category as humans and yeast.
The designer chromosome that made its debut in brewer’s yeast permits researchers to make fundamental changes to them, leading to the production of wholly new drugs and other products. Though yeast is already part of the process used to produce biomedical products, this newfound power to change their chromosomes with such definitiveness has ushered a whole new set of possibilities.
By Aruna Iyer