Summary: Researchers analyzed the DNA sequences of 240 mammalian species, showing how comparative genomics can shed light on how specific species perform exceptionally and help scientists better understand the functional parts of the human genome.
By identifying regions of the genome that are most conserved among mammalian species, they have pinpointed the genetic basis for unusual mammalian traits such as the ability to hibernate or detect faint scents from miles away.
They also found genetic variants that are more likely to play a causative role in both rare and common human diseases.
Source: Broad Institute
Over the past 100 million years, mammals have adapted to almost every environment on Earth. Scientists from the Zoonomia project have cataloged the diversity of mammalian genomes by comparing DNA sequences from 240 species that exist today, from the aardvark and the African savannah elephant to the yellow-spotted rock hyrax and the zebu.
This week in several newspapers in a special edition of Sciencethe Zoonomia team has shown how comparative genomics can not only shed light on how certain species perform exceptionally, but can also help scientists better understand the functional parts of our genome and how they can influence health and disease.
In the new studies, the researchers identified regions of the genome, sometimes just single letters of DNA, that are most conserved or unchanged across mammalian species and millions of years of evolution — regions likely to be biologically important.
They also found part of the genetic basis for unusual mammalian traits like the ability to hibernate or sniff out faint scents from miles away. And they identified species that may be particularly threatened with extinction, as well as genetic variants that are more likely to play a causative role in rare and common human diseases.
The findings come from analyzes of DNA samples collected from more than 50 different institutions worldwide, including many from the San Diego Wildlife Alliance, which provided many genomes from threatened or endangered species.
More than 150 people from seven time zones have contributed to the Zoonomia project, which is the world’s largest resource for comparative mammalian genomics. The effort is being led by Elinor Karlsson, director of the vertebrate genomics group at MIT and Harvard’s Broad Institute and professor of bioinformatics and integrative biology at UMass Chan Medical School, and Kerstin Lindblad-Toh, scientific director of vertebrate genomics at the University of Broad and Professor of Comparative Genomics at Uppsala University in Sweden.
“One of the biggest problems in genomics is that people have a really big genome and we don’t know what it does,” Karlsson said. “This bundle of paper really shows what you can do with this kind of data and how much we can learn from studying the genomes of other mammals.”
Exceptional properties
In one of the studies published today, co-first authors Matthew Christmas, a researcher at Uppsala University, and Irene Kaplow, a postdoctoral researcher at Carnegie Mellon University, along with Karlsson, Lindblad-Toh and collaborators found that at least 10% of the human The genome is highly conserved across species, with many of these regions occurring outside of protein-coding genes. More than 4,500 elements are almost perfectly conserved in more than 98% of the examined species.
Most of the conserved regions – which have changed more slowly than random fluctuations in the genome – are involved in embryonic development and the regulation of RNA expression. Regions that changed more frequently shaped the interaction of an animal with its environment, for example through immune responses or the development of its skin.
The researchers also located parts of the genome linked to some extraordinary traits in the mammalian world, such as extraordinary brain size, superior sense of smell and the ability to hibernate during winter.
With biodiversity conservation in mind, the researchers found that mammals with fewer genetic changes at conserved sites in the genome were at higher risk of extinction. Karlsson and Lindblad-Toh say that even just one reference genome per species could help scientists identify endangered species, since fewer than 5% of all mammalian species have reference genomes, although more work is needed to develop these methods.
insights into diseases
In another study, Karlsson, Lindblad-Toh and colleagues used the mammalian genomes to study human traits and diseases. They focused on some of the best conserved single-letter genomic regions discovered in the first paper and compared them to genetic variants that scientists had previously linked to diseases such as cancer using other methods.
The team found that their evolutionary conservation-based annotations of the genome revealed more connections between genetic variants and their function than the other methods. They also identified mutations likely to be causative 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 disease risk.
The co-first authors of this study were Patrick Sullivan, Director of the Center for Psychiatric Genomics at the University of North Carolina Medical School, Chapel Hill and Professor of Psychiatric Genetics at the Karolinska Institutet in Sweden; Jennifer Meadows, genetics researcher at Uppsala University in Sweden; and Steven Gazal, assistant professor of population and public health sciences at the Keck School of Medicine at the University of Southern California.
A world of questions
A third study, co-led by Steven Reilly, an assistant professor of genetics at Yale University, and Pardis Sabeti, an institute member at Broad, examined more than 10,000 genetic deletions specific to humans, using both zoonomia data As well as experimental analyzes have been used and linked some of them to the function of neurons.
Other Zoonomia papers released today showed that mammals diversified before the mass extinction of dinosaurs; discovered a genetic explanation for why a famous 1920’s sled dog named Balto was able to survive the rugged Alaskan landscape; discovered human-specific changes in genome organization; used machine learning to identify regions of the genome associated with brain size; described the evolution of regulatory sequences in the human genome; focused on DNA sequences that move around the genome; discovered that species with historically smaller populations are now at greater risk of extinction; and compared genes between nearly 500 species of mammals.
For Karlsson, Lindblad-Toh and the researchers who have been sequencing mammalian genomes for Zoonomia or its precursor projects since 2005, these studies — and the range of questions they answer — represent only a fraction of what’s possible.
“We are very excited about sequencing mammalian species,” said 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 diseases.”
About this genetic research news
Author: press office
Source: Broad Institute
Contact: Press Office – Broad Institute
Picture: The image is attributed to Neuroscience News
Original research: Open access.
Zoonomia by Sacha Vignieri. Science
Abstract
zoonomy
Mammals are one of the most diverse classes of animals, ranging both in size over many orders of magnitude and in shape – almost the limits of one’s imagination. From the dawn of science, it has been of interest to understand when, how, and under what selective pressures this variation evolved.
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