Taiwan researcher scours DNA sequences for treasures

Genetic analysis offers new directions for drug development, disease prevention

New study from Tsai's lab to be published in September/October. (Academia Sinica photo)

New study from Tsai's lab to be published in September/October. (Academia Sinica photo)

TAIPEI (Taiwan News) — Since the grand reveal of the completed human genome sequence in 2001, scientists have flocked to decipher the genetic blueprint that makes us who we are and how our genetic heritage can improve life.

Although people use the term "race" to categorize various ethnic groups, based on genealogy and appearance, each person has a mere 0.1-percent genetic difference from others. Moreover, as DNA sequencing applies to a wide range of species, the genetic similarity between humans and other creatures is also quite staggering. For example, 90 percent of our DNA is similar to the Abyssinian house cat, and 92 percent with mice.

Similar genes indicate humans and the Abyssinian cat have a shared ancestor. (Flickr, Wietse Jongsma photo; Unsplash photo)

On the other hand, even though DNA sequencing can read out the order of the chemical bases — the long A,T,C,G pairs — this will not directly give an answer to identifying the genes that express eye color or cause cancer. To do this, scientists have to compare sets of genomes to crack open the mystery of the DNA codes.

"Around 20,000 genes now identified across the human genome serve as a platform (to identify the cause of diseases)," said Tsai I-sheng (蔡怡陞), Associate Research Fellow at Academia Sinica's Biodiversity Center.

For instance, if scientists discover several genes in a human that might link to a particular ailment and find mice also carrying similar genes, they can conduct experiments on mice instead of humans to figure out whether these genes are truly responsible for certain illnesses.

Tsai's lab specializes in using genomic tools to study the mechanisms of pathogenicity and parasitism. He relies on genetic sequencing to explain the evolutionary trajectory of parasites and how the regulation of gene expression — a process in which cells produce specific proteins by reading the information coded in DNA — helps them survive in various environments.

Process of gene expression (National Cancer Institute image)

In one study that Tsai co-authored in 2013, researchers proved that gene expression strongly fluctuated throughout the life of Haemonchus contortus, also known as the barber's pole worm. This roundworm parasite causes anemia, lethargy, and even death to infected sheep and goats

A voracious blood-feeder, the worm is born in the feces of the host and grows into an adult worm in about three weeks. The study showed the genes being upregulated — a process by which a cell increases the number of cellular components, such as RNA or protein — during the development of embryonic eggs to primitive larvae are associated with muscle development and motor activity.

Once the host ingests the worm, it then enters its blood-feeding stage, and the genes relating to locomotion and metabolic processes are activated. Genes relating to the binding of oxygen and sugars also spring into action.

These gene expressions match the needs of the parasitic worm throughout its life cycle. Understanding this mechanism offers an alternative approach to curing infected livestock.

Example of parasite’s life cycle (CDC image)

"To a certain degree, these parasites understand our bodies more than we do," Tsai explained. He also referred to another study that confirmed whipworms were capable of regulating the immune system of hosts to avoid being attacked.

"People used to think they could simply kill the parasites with medicines and let the animals excrete them out, but altering the host's immune system could be a totally different approach that achieves the same outcome."

Warm, humid climates favor growth of barber's pole worms (left) and increase the chances of infection (Wiki commons image; Unsplash image)

Tsai's lab is also working on solving the mystery of how parasitism occurs. For example, why these parasitic flatworms decided to live on other creatures tens of thousands of years ago and evolved into their current form through the gain and loss of certain body traits.

Parasites like tapeworms have neither a mouth nor a digestive tract. They also lack a circulatory system and a specialized organ for gas exchange.

Although genetics is a broad field, Tsai believes its core values and analytical method align with those of general biology. Genomic analysis is best seen, he said, as a supplementary tool that is applicable in all kinds of domains, including evolution, medicine, and agriculture.

"If the genome is a user guide of each species, then the study of genomes is to figure out how to print and understand this guide," Tsai wrote.

Tsai I-sheng from Academia Sinica (Taiwan News photo)