Pakistan sequences genome of medically important indigenous fly for the first time

Biologists have sequenced first ever genome draft of any insect in Pakistan which is a tiny fly widely used for medical research in thousands of labs across the world.

A group of scholars led by Dr Mushtaq Hussain, at the "Fly Research Lab and Stock Center" in College of Biotechnology at the Dow University of Health Sciences (DUHS), developed mutant Drosophila of Pakistani origin and the other team sequenced the genome of the humble creature.

Drosophila melanogaster is common fruit fly often referred as “Cinderella of Genetics” shares 60% genetic similarities and 75% of disease related genes of humans. These qualities make the little fly as perfect lab model for further research on human diseases and even for new drugs testing. Over 500 human diseases have been successfully modelled in the little fly so far.

For over a century Drosophila, helped us understand heredity, genes, chromosomes, developmental patterns, immunity, physiological processes, population genetics, evolution, and has served as an experimental model to study human diseases. It is also dubbed as “human with wings.”

The little fly has helped several Drosophilists – researchers engaged in Drosophila studies – to win six Nobel Prizes, three in the past and three awarded in the current century!

ANU-1: Drosophila of Pakistani origin

Recently, the Dow Fly Research Lab and Stock Center published the first ever complete genome draft of Drosophila of Pakistani origin.

Back in September 2021, under the supervision of Dr Mushtaq Hussain, Anusha Amanullah, then a post graduate student, observed a mutant fly different from normal (wildtype) Drosophila.

From white eyes to curly wings, the variants developed at the ‘Fly Research Lab and Stock Center’ in College of Biotechnology at the Dow University of Health Sciences (DUHS). PHOTO: DUHS

Anusha observed the fly without its main feature – the big bright red eyes. She first thought it was a creepy creature without head wriggling in bottle. But soon she realized that the it had white eyes as the mutant lacks those normal red eyes.

Anusha Amanullah carefully picked the fly and bred in different permutations or to determine whether genetic association with a trait is significant. The Eureka moment came in third generation when she made various male and female white eyes flies.

So, that was a first mutant fly developed in Pakistan. Then separate line or breed of Drosophila was made and named by Professor Hussain as ANU-1 after its discoverer, Anusha. Later, she was offered a fully funded PhD scholarship from Dow University of Health Sciences to carry out her PhD studies at the Nuffield Department of Clinical Medicine, at the Oxford University.

"The availability of whole genome draft of the indigenous Drosophila melanogaster opens a new horizon in relation to modelling human diseases in indigenous fruit fly strains within Pakistan by employing conventional and modern gene editing tools,” said Anusha Amanullah.

Drosophila Draft

Like a relay race, Anusha passed the research baton to other colleagues to further explore the genetic makeup of new Pakistani mutant.

In 2023, a post graduate and another BS final year research student – Iffat Waqar and Sukaina Arshad, respectively sequenced and developed the complete draft of the genome of ANU-1 under the supervision of Prof. Hussain.

The researchers behind different variants of fruit fly at the ‘Fly Research Lab and Stock Center’ in College of Biotechnology at the Dow University of Health Sciences (DUHS).PHOTO: DUHS

The team used state of the art, “HISeq platform of Next Generation Sequencing”, and deciphered the fly genome after almost six months of tireless work. Then the full genome draft was submitted to the National Center for Biotechnology (NCBI) US, for review. Recently, it has been reviewed and posted on the website under the Bioproject id: PRJNA1017144.

Economic fruits of fruit fly

The several years of research put Pakistan on the map of Drosophila discoveries. It is the first fully genome draft of any Pakistani insect let alone the fruit fly. Iffat and Sukaina also identified several genetic variations never been reported in any Drosophila genome elsewhere in the world.

The white eye Drosophila is commonly used to study brain and neurodegeneration research across major lab benches as an effective low-cost model. The fly is far cheaper as compared to other expensive mammalian animals or lab rats.

This made the fly as an economic commodity as many companies sell the humble flies to earn a lot of money. The Bloomington Fly Stock Center, US is the largest supplier of normal and mutant flies. The Center sells over 4000 fly breeds or lines per week for nearly at the cost of $100 for a pair of flies. The Pakistani fly has also the potential commercial aspect as well.

Development of such lines in Pakistan will not only help in starting a research niche for this highly cost-effective model organism in the country compared to the relatively expensive model system. Additionally, compared to mice or any other mammalian or vertebrate model system there is nearly no ethical concern while working on flies.

"The availability of whole genome draft of the Indigenous Drosophila melanogaster opens a new horizon in relation to modelling human diseases in indigenous fruit fly strains within Pakistan by employing conventional and modern gene editing tools," Professor Hussain told The Express Tribune.

Globally, top universities typically maintain dedicated fly labs, with over 2,000 in total. In Pakistan, however, research on fruit flies has been notably scarce. For an extended period, it has been limited to a single private institution, the Lahore University of Management Sciences, where Prof. Muhammad Tariq heads the lab.

Fly incubator shows different variants of Drosophila Melanogaster. PHOTO: DUHS

After 10 years, at Dow College of Biotechnology of Dow University of Health Sciences, research has been started on fruit flies under the supervision of Prof. Musthaq Hussain. The small lab has now been advanced to a much bigger facility comparable to any other international fly lab.

In addition to these, other lines representing different human diseases are also been developed at the Fly Lab of Dow University of Health Sciences with flies completing lacking eyes, flies with only one and flies with noticeably curved wings. These lines are developed by a post-graduate student Ayesha Aslam.