New research reveals the genetic diversity and evolutionary history of primates

New research reveals the genetic diversity and evolutionary history of primates

The rich genetic diversity and evolutionary history of primates – the group that includes apes, apes, lemurs and ourselves humans – has been revealed for the first time in a new research paper released today. And the findings will help us better understand genetic diseases, human health, how we evolved, and even the mutations that make us uniquely human.

New research reveals the genetic diversity and evolutionary history of primates
White fronted capuchin, Cebus unicolor, Manaus, Brazil. Image credit: Rebecca Still.

Academics from around the world, including the University of Salford, have sequenced the genomes of more than 200 primate species, almost half of the current total, to create the first global catalog of genetic diversity among primates. Published today in the magazine Science, the new data will open a new era in primate research. While previous primate genetic research has focused primarily on relatively small parts of the genome, such as specific genes, this study is the first to publish a diverse sample of entire genomes across the primate family tree. By way of comparison, if genes are paragraphs and chromosomes are chapters, the entire genome is the entire book that includes all of an organism’s DNA.

Working with 75 colleagues in Spain, Germany, the United States, Brazil, among 20 other countries, the Salford team contributed 205 samples for a total of 77 species, or more than 30% of the species analyzed in the new study, from their vast genetic collection of primates, the only one of its kind in Europe. The Salford team also used information from the fossil record in combination with genome sequences to produce a new best primate family tree to date. The results created an accurate picture of how all the different branches, including humans, are connected to each other and when these branches separate from each other.

Professor Jean Boubli, chair of the chair in tropical ecology and conservation at the University of Salford, one of the authors of the papers and a principal investigator from the Primate Conservation Sequencing Consortium (PCSC) who led this research, said: “This is a real game changer in the study of many aspects of primate evolution. And it’s up to conservation. Many of these species are under threat and the findings here could help with conservation efforts. It’s a fantastic collaboration that will open many doors for future research.”

This study shows the power of entire genomes for understanding primate diversity and how primates evolved over time. We now have a high-quality primate family tree, using by far the largest dataset ever published. It shows how primates have diversified over the past 60 million years, from their origin a few million years after the extinction of the dinosaurs to the present day. For the first time, we have a really solid time scale for these evolutionary events and now we can start trying to identify what might have caused them.”

Dr Robin Beck, Biology Reader, University of Salford, fossil and phylogenetic expert and co-author of the paper.

Dr Dorien de Vries is a postdoctoral researcher at the University of Salford who has used her expertise in the primate fossil record to identify fossils that could be used to calculate the timescale of the new primate family tree . She said: “Knowing the history of primate evolution provides a great framework for many types of future research. For example, only then can you calculate and compare mutation rates between different groups of primates (as we did in the paper) which has important implications for rates of evolution and what differences are there between small and large primates, among many other questions.

Dr Mareike Janiak, a former Salford postdoctoral researcher now at the Canadian Center of Computational Genomics, combined this fossil data with genomic data to calculate when different groups of primates developed, an analysis that was only possible using a large supercomputer. Due to the sheer size of the data involved, even on a supercomputer the analysis took a full month to complete.

This was a large collaborative effort that was made possible by combining the expertise of researchers from many backgrounds, including field biologists, fossil experts and computer scientists. Just a few years ago there were only about 20 primate genomes available, so this is a huge leap forward for the industry.”

Dr. Mareike Janiak.

Professor Ian Goodhead, Associate Dean for Research and Innovation for the School of Science, Engineering and Environment and Genomics researcher, said: “This study highlights how effective it is to bring multiple disciplines together to help answer some of science’s toughest questions. Salford University has invested nearly £1 million in computational and molecular biology in recent years, and it’s great to see this benefit for both researchers and students; studies like this highlight how future biologists will work. In the coming years we hope to further expand this work to make further contributions to conservation efforts in the Amazon and more widely.”

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Research in the era of personalized medicine

Research in the era of personalized medicine

In early 2017, a neurologist at Boston Children’s Hospital named Timothy Yu began work on the most ambitious project of his life: devising and synthesizing an experimental drug for a dying child, within a few months.

Weeks earlier, Yu had been forwarded a desperate plea made on Facebook by a woman named Julia Vitarello. Her daughter Mila, then just five years old, had been diagnosed with Batten disease: a rare but devastating neurodegenerative disease that combines the symptoms of Parkinson’s disease, dementia and epilepsy. Worse, Mila’s form of Batten disease was driven by a unique genetic mutation, meaning no existing experimental therapy would work.

Rather than accepting her daughter’s fate, Vitarello became an activist, setting up a foundation in her daughter’s name. Through crowdfunding, she has raised more than $3 million ($2.4 million) to fund a new gene therapy. This eventually led her to Yu.

After sequencing Mila’s genome to identify the responsible mutation, Yu suggested developing a drug called “antisense oligonucleotide.” This relatively new treatment approach has recently been used to create a therapy for another rare disease called spinal muscular atrophy. Antisense oligonucleotides act by binding to the molecules produced by the mutated DNA, correcting their behaviour. But in this case it would be different. Yu allegedly created a custom antisense oligonucleotide designed exclusively for Mila.

At the time, it was the boldest drug development timeline ever attempted: synthesizing new drugs typically takes years instead of months. But in the winter of 2017, the drug, which was called “milasen”, was ready.

“I didn’t want my daughter to be the first to receive personalized medicine,” Vitarello says, speaking to the BBC from her home in Colorado, US. “I was hoping we could find the mutation that was causing her disease, but then milasen, the drug Tim Yu developed for Mila, showed what is possible. We have the ability to find the underlying genetic cause of a disease and then pinpoint a drug to it, even if it’s unique to only one person.It was only after Mila started getting the drug that I started to really understand what a big deal it was.

Over the next four years, the treatment helped stop the progression of Mila’s condition and improved her quality of life. “Her legs got stronger so she could climb the stairs with my help,” says Vitarello. “She Laughed and smiled at funny things in books and songs. She Thought people sneezing was hilarious.”

Unfortunately, it came too late. The disease, already in an advanced stage, eventually returned. Mila passed away on February 11, 2021, aged just 10.

His mother still struggles with the loss. “What if he started taking the drug two months earlier, when he was still speechless and not having seizures. What if he’s been on it two years earlier or since birth? I have really difficult days. It comes unexpectedly, in waves.”

But two years later, Mila’s story began to spawn its own legacy. Unknown to her mother at the time, milasen’s development was followed by geneticists from around the world. They saw it as a seminal case for how genomics-based personalized medicine could be used to tackle rare diseases. “This story is a really powerful example of what’s possible,” says Richard Scott, chief medical officer at Genomics England, which is run by the UK department of health, and a consultant at Great Ormond Street Hospital in London.

Mila’s story illustrates both the promise of personalized medicine, but also some of its frustrations. In theory, therapies targeting a person’s genetic makeup should be more effective and have fewer side effects. But in practice, personalized medicine is often irregular and expensive, and there are often simpler solutions. It also requires people to trust governments and companies with their genomic data, while the regulatory environment around drugs is ill-equipped to deal with therapies designed for just one person. Obtaining the safety and efficacy data needed for regulatory approval usually requires clinical trials involving hundreds, if not thousands of people.

However, researchers are still trying and now it looks like there could be some real progress.

#Research #era #personalized #medicine