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Baked: an yeast gene from scratch

New Delhi, March 27: Indian biologists in the US have helped synthesise the world’s first designer chromosome for bakers’ yeast, achieving a milestone towards creating an artificial genome for an organism used for centuries to make bread and beer.

An international team of scientists at the Johns Hopkins University (JHU) and other institutions has deleted, inserted, and scrambled genetic alphabets to construct a synthetic version of the yeast’s third chromosome and shown that it can substitute for the original one.

“We’ve made a chromosome from scratch using non-living chemicals and shown that it can keep yeast cells alive and functional,” Narayana Visu Annaluru, a research associate at the JHU School of Public Health and a team member, told The Telegraph.

The feat is being described as a major step towards the design and synthesis of novel genomes for a class of organisms called eukaryotes that includes all living things — from fungi to plants to animals to humans — whose cells house nuclei.

While other research teams have created bacterial genomes and sections of chromosomes over the past five years, the task of constructing a full synthetic chromosome for yeast is far more challenging because the yeast is a more complex organism than bacteria.

The scientists made over 500 alterations to the genetic base of the yeast’s third chromosome, removed repeating sections of 47,841 genetic alphabets, and deleted genetic material labelled as junk DNA to construct the synthetic chromosome they have named synIII.

“When you change the genome, you’re gambling — one wrong change can kill the cell,” said Jef Boeke, director of the Institute for Systems Genetics at New York University’s Langone Medical Centre, who led the research effort.

“We’ve shown that yeast cells that carry synthetic genes behave almost identically to wild yeast cells; only they now possess new capabilities and can do things that wild yeast cannot,” he said in a media release.

The scientists described their work today in the US journal Science.

“This is a very, very important advance in the field of yeast genomics,” said Sagar Lahiri, a senior research fellow at the Indian Institute of Chemical Biology, Calcutta, who was not associated with the work but specialises in yeast research.

“This work will provide the building blocks for the knowledge required to create artificial life forms in the future,” Lahiri told The Telegraph.

The yeast, a model eukaryotic organism, shares about a third of its 6,000 genes with humans. Yeast cells containing synthetic chromosomes, Annaluru said, could facilitate certain studies on how genes interact with each other that are otherwise not possible with wild yeast strains.

“The yeast with synIII has a built-in scrambling system to delete and shuffle random genes on demand,” Srinivasan Chandrasegaran, an Indian-origin professor at Johns Hopkins and a senior investigator in the research effort, told this newspaper.

“This feature could be used to develop new yeast strains that may be optimised for (efficient) production of antibiotics, drugs, or even better beer,” said Chandrasegaran, who was born in Puducherry and studied in Chennai before moving to the US.

The researchers say that new yeast strains could also be used to increase the efficiency of producing biofuels such as ethanol, butanol, or biodiesel.

“I’m particularly excited about scrambling the genome to develop a yeast strain that can tolerate high levels of ethanol,” said Annaluru, who was born near Nellore and studied at Sri Venkateswara University in Tirupati before pursuing research in Japan and the US.

The scientists say they picked chromosome III first because it is the smallest among the 16 chromosomes found in yeast. But they hope to continue constructing more synthetic yeast chromosomes.

The Pondicherry Biotech Limited, a private institution, provided the US collaborators optimised protocols for the synthesis of intermediate mini-segments that were needed to construct the left arm of synIII.

The company is now trying to raise funds from public and private foundations in India to synthesise more yeast chromosomes, Chandrasegaran said.

“The aim is to construct the synthetic version of yeast chromosome XVI in India.”