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UCD genome research recognised in special issue of Science

Posted 12 May, 2023

An international research effort comparing DNA sequences from 240 species to reveal what makes the human genome unique has been recognised in a special edition of one of the world's top academic journals.

The Zoonomia Project, which includes researchers from UCD Professor Emma Teeling’s BatLab and Dr Graham Hughes’ Bioinformatics and Comparative Genomics research group in the UCD School of Biology and Environmental Science, have had 11 papers published in a special issue of Science.

Comparing DNA sequences from 240 species alive today, the scientists involved not only showed how certain animals achieve extraordinary feats but also pinpointed key parts of the human genome that have remained unchanged after millions of years

“This represents an extraordinary breakthrough in our understanding of the genetic basis of the unique traits of humans and other mammal,” said Professor Teeling, Full Professor of Zoology, University College Dublin.

“These breakthroughs were only possible through the extensive international collaboration of the Zoonomia team of scientists, which we were privileged to be a part of.”

In the new published studies, researchers identified regions of genomes, sometimes just single letters of DNA, that are most conserved (unchanged) across mammalian species and millions of years of evolution.

Along with identifying species that may be particularly susceptible to extinction, they also found part of the genetic basis for uncommon mammalian traits such as the ability to hibernate or sniff out faint scents from miles away, as well as those genetic variants likely to play a role in rare and common human diseases such as cancer and motor neuron disease.

“Ireland continues to be a key player in driving genomic research to better understand ourselves and the natural world around us,” said Dr Hughes, UCD Ad Astra Fellow and Director of the UCD Centre of Bioinformatics.

“We’re only scratching the surface of what mammal genomes can tell us about how shared and distinct mammal traits have evolved. This information can provide new genomic perspectives on human traits or diseases.”

The largest comparative mammalian genomics resource in the world, the Zoonomia Project had more than 150 scientists from over 50 different institutions contributed to its work.

The global project is led by Professor Elinor Karlsson, director of the vertebrate genomics group at the Broad Institute of MIT and Harvard, and a professor of bioinformatics and integrative biology at the UMass Chan Medical School; and Professor Kerstin Lindblad-Toh, scientific director of vertebrate genomics at the Broad and a professor of comparative genomics at Uppsala University in Sweden. 

“One of the biggest problems in genomics is that humans have a really big genome and we don’t know what all of it does,” said Professor Karlsson. “This package of papers really shows the range of what you can do with this kind of data, and how much we can learn from studying the genomes of other mammals.”

Exceptional traits

One of the studies published in Science found that at least 10% of the human genome is highly conserved across species, with more than 4,500 elements essentially unchanged across some 98% of the species studied. 

Most of the conserved regions are involved in embryonic development and regulation of RNA expression. Regions that changed more frequently shaped an animal’s interaction with its environment.

The researchers found those genome linked to a few exceptional traits in the mammalian world, such as extraordinary brain size, superior sense of smell, and the ability to hibernate during the winter. 

“The sense of smell is one of the key ways we interact with our environment”, said Dr Hughes who’s research team, including PhD students Colleen Lawless and Louise Ryan, carried out the genomic exploration of the sense of smell in Zoonomia. 

“We humans use smell when enjoying a meal or buying colognes and perfumes. But in the wild, smelling a predator in advance, or being able to sniff out sources of food can be the difference between life and death. As trivial as smell may be to us in our day-today lives, it’s an essential evolutionary adaptation in the animal kingdom.”

The Hughes team identified the number of genes encoding the sense of smell across all species, highlighting mammals with the highest and lowest capacity for smell, according to their genome.

Elephants have far more genes encoding the sense of smell compared to other mammals, while primates, dolphins and whales have the fewest, reflecting a reliance on alternative modes of sensory perception such as sight and echolocation. 

“Humans have roughly 370 functioning genes encoding smell receptors in comparison to the more than 900 found in the rhinoceros or 1765 in elephants,” said Dr Hughes.

“Most mammals have access to a sensory space far beyond that which any human could ever contemplate. Understanding how smell has evolved at the genomic level helps us contextualise key environmental and ecological sensory drivers that are crucial in mammalian evolution”.  
Disease insights

In another study the mammalian genomes were used to study human traits and diseases. It identified mutations likely causal in both rare and common diseases including cancer, and showed that using conservation in disease studies could make it easier to find genetic changes that increase risk of disease.

“No matter what nasty disease humans might encounter, odds are there’s an animal out there that has evolved ways to avoid, mitigate, fight, or recover from it,” said Dr Hughes, who helped compare all known human variants associated with disease to the same genomic regions in other mammals. 

“Mother nature has already figured out how to deal with diseases over many millions of years of tinkering via natural selection. These secrets are hidden in the genome.”

Adding: “If you find a genetic variant occurring naturally in a mammal that would cause a disease in humans, it’s worth investigating it further why isn’t that mammal getting sick? How are they managing to mitigate the consequences of that variant? Is it actually beneficial for them? Can we use that to explore new human treatments?” 

One such variant identified by Dr Hughes in the SOD1 gene can cause Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease, in humans but occurs naturally in rhinoceroses, horses and tapirs. Despite this, these species don’t seem to manifest classic symptoms of motor neuron disease. 

“This suggests that these species have developed a means to avoid the negative impacts of having such a variant. Figuring out how may lead to new, novel therapies and treatments for this disease in the near future,” he added.

Other Zoonomia papers published in the special edition of Science revealed that mammals diversified before the mass dinosaur extinction, led by UCD graduate and first author Dr Nicole Foley, currently a research scientist at Texas A&M.

For Karlsson, Lindblad-Toh, and the researchers who have been sequencing mammalian genomes for Zoonomia, or its precursor projects since 2005, these latest findings showcase only a fraction of what is possible.

“We’re very enthusiastic about sequencing mammalian species,” said Professor Lindblad-Toh. “And we’re excited to see how we and other researchers can work with this data in new ways to understand both genome evolution and human disease.”

“This project provides the frame-work and template for future large comparative genomic studies and successful international collaboration to truly uncover the how our genome functions and how we have evolved…the future is bright,” added Professor Teeling.

The Zoonomia Project was supported in part by the National Institutes of Health, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the National Science Foundation, Science Foundation Ireland, and the Irish Research Council.

By: David Kearns, Digital Journalist / Media Officer, UCD University Relations

To contact the UCD News & Content Team, email: newsdesk@ucd.ie