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"MUC6" gene becomes the key to domestication to uncover the "unsolved mystery" of goats

author:Globe.com

Source: China Youth Daily

"Humans have used billions of goats, over tens of thousands of years, to do a survival of the fittest experiment, which is a valuable asset for humans to understand how mammals fight off disease and change neural behavior." According to Jiang Yu, a professor at Northwest A & F University, by studying the key genetic changes of wild animals after they are domesticated, it is helpful to gain insight into hundreds of goat breeds with different morphological characteristics, production traits, disease resistance and environmental adaptability, which is "very important for animal molecular breeding."

When you think of goats, a sense of closeness arises. Interestingly, goats that are so "intimate" with humans carry an "unsolved mystery" that has always plagued humans – what has led to the most critical genetic changes in the evolution of domesticated goats over more than 10,000 years after the wild ancestors of goats were domesticated?

As one of the earliest domesticated livestock by humans, goats lived in the Fertile Crescent of West Asia as far back as 11,000 years ago and were called "the cows of the poor" by the ancient Assyrians who bred there. Today, the high-quality milk, meat and velvet provided by goats have become the most high-end livestock products for human beings.

By the 16th century, christopher Columbus and the pilgrims of the Mayflower had also experienced risks along with them when they crossed the Atlantic Ocean. Even on islands around the world, goats that are accidentally herded have survived as a tenacious species after withstanding terrible threats such as extreme climatic environments and diseases.

Not long ago, on May 20, a research result related to goats by Professor Jiang Yu's team at Northwest A & F University, "The Origin of Goat Domestication Genes", appeared on the cover of Science Advances, a sub-journal of Science magazine. This study reveals an interesting conclusion – the root cause of the goat's "strong" stems from the fact that it obtained the MUC6 gene of other species through hybridization. On the day the paper was published, the journal Science also conducted an interview on the results.

The gene, called "MUC6," comes from a West Caucasian wild sheep species that has been separated from wild goat species for more than a million years. The MUC6 gene, along with other domestication genes, helped the goats to be successfully domesticated at the earliest stage and were widely farmed around the world.

The most critical genetic alteration in domestication of goats is the disease resistance gene

"Goats were domesticated from wild goat populations and began about 11,000 years ago in that fertile land, the eastern and western parts of the Crescent, which is now Iran and Turkey." Jiang Yu, born in 1983, has collaborated to complete the reference genome construction of the world's first goat and the first sheep, and identified a series of ruminant trait-related genes. He told reporters: The domestication of goats is crucial in the entire process of agricultural development and the advancement of civilization.

Wild goats and sheep are domesticated and provided with abundant living materials such as meat, milk, wool, and skin. The process of domestication became a crucial production activity during the period of agricultural civilization. In China, archaeological excavations confirm that during the Longshan culture in 2000 BC, goats were already important domestic animals in human life. In the ancient literary work "Shijing, Xiaoya, No Sheep", which is more than 3,000 years old, "Who is said to be without sheep?" "Three Hundred Dimensional Herds" shows the scene when the sheep were flourishing.

Professor Jiang Yu, who has long been committed to animal genetics and breeding research, published the first paper on the "goat genome" in the journal Nature Biotechnology in 2013, and the first paper on the "wild goat genome" in 2015.

This time, he led the team to challenge the goat "unsolved mystery" again: after conducting sample collection and comparative analysis of genomic information from 164 domestic goats, 24 wild goats, 56 goat fossils, and 6 other wild sheep species around the world, they concluded that "the most important genetic changes in the domestication of goats are locked in the changes in the 'disease resistance genes'." ”

The MUC6 gene plays a key role

Collect, compare, analyze, demonstrate... This is a research project with a large system and a complicated program. Just the acquisition of massive research samples has consumed a lot of energy on the team.

The researchers invested in a vast sea of data searches, downloaded published European sheep data through the Internet, and collected samples of Chinese domestic sheep and wild sheep from zoos already available at the school and the Kunming Institute of Zoology of the Chinese Academy of Sciences. With the support of domestic archaeologists and the acquisition of ancient samples, a large number of samples and data were obtained by mail through extensive contacts with international collaborators.

One of the most important samples of these is from wild sheep from the West Caucasus. Currently, only a few thousand of this population of surviving wild sheep remain, distributed in Georgia. "In 1976, someone donated a West Caucasian wild sheep to a zoo in Europe, and after the wild sheep died, it was made into a specimen and stored in the French Museum of Natural History." Jiang Yu recalls: In 2017, when he visited the laboratory of Daniel G. Bradley, a professor at Trinity College Dublin, he learned that he had obtained a small bone sample of a West Caucasian wild sheep from the Paris Museum. Based on a pleasant collaboration with Professor Daniel in the study of cattle origins in China, Jiang Yu finally obtained the genomic data of this sample.

The acquisition of ancient sheep research samples also has an interesting story. At that time, researchers at the Shaanxi Archaeological Research Institute were willing to provide Jiang Yu's research group with samples of ancient Chinese sheep, but at the same time hoped that "a complete bone specimen of modern sheep could be obtained from the academy." Therefore, Jiang Yu asked his mother to buy and slaughter two adult goats, one male and one female, and cooked them in a large pot, leaving all the bones of the two sheep intact. After drying, two complete sheep bone specimens were mailed to the Archaeological Institute.

With the help of NTU's high-performance computing platform, the team was able to complete a huge amount of data analysis work and obtain the final data results after carefully designing a large number of bioinformatics sequence comparison, statistical analysis and modeling analysis templates.

"For goats, the first few hundred or even millennia of domestication was a dramatic transition from free-roaming wild environments to high-density, disease-prone anthropogenic environments." Jiang Yu said: Due to the mixed breeding of a variety of livestock, the cross-contamination of manure is serious, "which makes it very difficult to maintain and expand the livestock population." ”

In the process of complex genomics research, MUC6, a disease-resistant gene that Jiang Yu called "vital", entered the team's field of vision. "This gene has played a big role in the domestication of goats – almost every domestic goat has a domesticated type of MUC6 gene, and it is not from the direct wild ancestors of domestic goats , wild goats in the mountains of Iran and Turkey , but from a wild sheep breed called "West Caucasus Tur" in the warm and humid environment of the Black Sea coast.

"The MUC6 gene shows a peculiar ability - it encodes the mucin present on the mucosa on the surface of the gastrointestinal tract, can act as a physical barrier to innate immunity, and activates the acquired immune system, playing a role in alleviating the survival and parasitism of various parasites in the gastrointestinal mucosa, thereby effectively improving the immune function of the animal body." Jiang Yu explained further.

By hybridizing with the West Caucasus Tur sheep breed, the domesticated version of the MUC6 gene had infiltrated the goat genome at least 7200 years ago and began to spread. Because the MUC6 gene will improve the gastrointestinal anti-parasite ability of the sheep, this makes the genotype widely spread to more than 60% of the world's domestic goat genome in just 1000 years, replacing the original MUC6 gene of domestic goats, making goats more suitable for survival in human environments.

"The speed of communication and breeding in prehistoric humans is unimaginable, and it also supports the extreme desire to acquire healthy animals with disease-resistant genes." Jiang Yu said.

Keep exploring and challenge more "unknowns"

Melinda Zede, an archaeologist at the National Museum of Natural History, commented in the journal Science: "This finding highlights the importance of hybridization with wild populations in the early stages of domestication and provides an example of how domesticated crops and livestock can improve their adaptive capacity and thus spread widely." ”

Not only that, Jiang Yu revealed: The team also found that "more than 99% of the gene pool of domestic goats is contributed by wild goats." But there are at least 112 other fragments from other wild goat relatives, such as 'Tur' or 'Ibex'. In addition, there are 105 goats' own genetic seats, which are strongly artificially selected. These are important functional genes in the domestication of goats. ”

In the past, it was believed that the domestication of goats was mainly changes in economic traits such as pigmentation and milk production, but Jiang Yu's team's research showed that the main changes in the early stage of goat domestication were changes related to nerve and pathogenic microbial resistance, "because these changes help the herd adapt to the man-made environment." ”

In addition, the team found that "changes in goat behavior are also one of the important domestication changes." Domestic goats are more docile and accessible to people than wild goats. "This may be related to behavioral genes and needs to be verified by further research in the future."

"Humans have used billions of goats, over tens of thousands of years, to do a survival of the fittest experiment, which is a valuable asset for humans to understand how mammals fight off disease and change neural behavior." In Jiang Yu's view, by studying the key genetic changes after the domestication of wild animals, it is helpful to gain insight into hundreds of goat breeds with different morphological characteristics, production traits, disease resistance and environmental adaptability, "which is very important for animal molecular breeding." ”

"We found 112 fragments from other wild goat relatives, and 105 goats whose own genetic seats were strongly artificially selected, and they must have had functional changes that are important to humans and goats." But at present, only a very small number have explicit functions, such as MUC6. Jiang Yu said, "In the next step, we will analyze the functions of these genomic regions through experiments and a variety of omics data analysis." ”