Posts tagged genomics
Posts tagged genomics
Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness
Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.
The overall number and nature of mutations—rather than the presence of any single mutation—influences an individual’s risk of developing schizophrenia, as well as its severity, according to a discovery by Columbia University Medical Center researchers published in the latest issue of Neuron. The findings could have important implications for the early detection and treatment of schizophrenia.
Maria Karayiorgou, MD, professor of psychiatry and Joseph Gogos, MD, PhD, professor of physiology and cellular biophysics and of neuroscience, and their team sequenced the “exome”—the region of the human genome that codes for proteins—of 231 schizophrenia patients and their unaffected parents. Using this data, they demonstrated that schizophrenia arises from collective damage across several genes.
“This study helps define a specific genetic mechanism that explains some of schizophrenia’s heritability and clinical manifestation,” said Dr. Karayiorgou, who is acting chief of the Division of Psychiatric and Medical Genetics at the New York State Psychiatric Institute. “Accumulation of damaged genes inherited from healthy parents leads to higher risk not only to develop schizophrenia but also to develop more severe forms of the disease.”
Schizophrenia is a severe psychiatric disorder in which patients experience hallucination, delusion, apathy and cognitive difficulties. The disorder is relatively common, affecting around 1 in every 100 people, and the risk of developing schizophrenia is strongly increased if a family member has the disease. Previous research has focused on the search for individual genes that might trigger schizophrenia. The availability of new high-throughput DNA sequencing technology has contributed to a more holistic approach to the disease.
The researchers compared sequencing data to look for genetic differences and identify new loss-of-function mutations—which are rarer, but have a more severe effect on ordinary gene function—in cases of schizophrenia that had not been inherited from the patients’ parents. They found an excess of such mutations in a variety of genes across different chromosomes.
Using the same sequencing data, the researchers also looked at what types of mutations are commonly passed on to schizophrenia patients from their parents. It turns out that many of these are “loss-of-function” types. These mutations were also found to occur more frequently in genes with a low tolerance for genetic variation.
“These mutations are important signposts toward identifying the genes involved in schizophrenia,” said Dr. Karayiorgou.
The researchers then looked more deeply into the sequencing data to try to determine the biological functions of the disrupted genes involved in schizophrenia. They were able to verify two key damaging mutations in a gene called SETD1A, suggesting that this gene contributes significantly to the disease.
SETD1A is involved in a process called chromatin modification. Chromatin is the molecular apparatus that packages DNA into a smaller volume so it can fit into the cell and physically regulates how genes are expressed. Chromatin modification is therefore a crucial cellular activity.
The finding fits with accumulating evidence that damage to chromatin regulatory genes is a common feature of various psychiatric and neurodevelopmental disorders. By combining the mutational data from this and related studies on schizophrenia, the authors found that “chromatin regulation” was the most common description for genes that had damaging mutations.
“A clinical implication of this finding is the possibility of using the number and severity of mutations involved in chromatin regulation as a way to identify children at risk of developing schizophrenia and other neurodevelopmental disorders,” said Dr. Gogos. “Exploring ways to reverse alterations in chromatic modification and restore gene expression may be an effective path toward treatment.”
In further sequencing studies, the researchers hope to identify and characterize more genes that might play a role in schizophrenia and to elucidate common biological functions of the genes.
Vast gene-expression map yields neurological and environmental stress insights
A consortium led by scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has conducted the largest survey yet of how information encoded in an animal genome is processed in different organs, stages of development, and environmental conditions. Their findings paint a new picture of how genes function in the nervous system and in response to environmental stress.
They report their research this week in the Advance Online Publication of the journal Nature.
The scientists studied the fruit fly, an important model organism in genetics research. Seventy percent of known human disease genes have closely related genes in the fly, yet the fly genome is one-thirtieth the size of ours. Previous fruit fly research has provided insights on cancer, birth defects, addictive behavior, and neurological diseases. It has also advanced our understanding of processes common to all animals such as body patterning and synaptic transmission.
In the latest scientific fruit from the fruit fly, the consortium, led by Susan Celniker of Berkeley Lab’s Life Sciences Division, generated the most comprehensive map of gene expression in any animal to date. Scientists from the University of California at Berkeley, Indiana University at Bloomington, the University of Connecticut Health Center, and several other institutions contributed to the research.
A large international consortium of researchers has produced the first comprehensive, detailed map of the way genes work across the major cells and tissues of the human body. The findings describe the complex networks that govern gene activity, and the new information could play a crucial role in identifying the genes involved with disease.
“Now, for the first time, we are able to pinpoint the regions of the genome that can be active in a disease and in normal activity, whether it’s in a brain cell, the skin, in blood stem cells or in hair follicles,” said Winston Hide, associate professor of bioinformatics and computational biology at Harvard School of Public Health (HSPH) and one of the core authors of the main paper in Nature. “This is a major advance that will greatly increase our ability to understand the causes of disease across the body.”
The research is outlined in a series of papers published March 27, 2014, two in the journal Nature and 16 in other scholarly journals. The work is the result of years of concerted effort among 250 experts from more than 20 countries as part of FANTOM 5 (Functional Annotation of the Mammalian Genome). The FANTOM project, led by the Japanese institution RIKEN, is aimed at building a complete library of human genes.
Researchers studied human and mouse cells using a new technology called Cap Analysis of Gene Expression (CAGE), developed at RIKEN, to discover how 95% of all human genes are switched on and off. These “switches”—called “promoters” and “enhancers”—are the regions of DNA that manage gene activity. The researchers mapped the activity of 180,000 promoters and 44,000 enhancers across a wide range of human cell types and tissues and, in most cases, found they were linked with specific cell types.
“We now have the ability to narrow down the genes involved in particular diseases based on the tissue cell or organ in which they work,” said Hide. “This new atlas points us to the exact locations to look for the key genetic variants that might map to a disease.”
Researchers may have been focusing on the wrong gene.
Scientists studying what they thought was a ‘fat gene’ seem to have been looking in the wrong place, according to research published today in Nature. It suggests instead that the real culprit is another gene that the suspected obesity gene interacts with.
In 2007, several genome studies identified mutations in a gene called FTO that were strongly associated with an increased risk of obesity and type 2 diabetes in humans. Subsequent studies in mice showed a link between the gene and body mass. So researchers, including Marcelo Nóbrega, a geneticist at the University of Chicago, thought that they had found a promising candidate for a gene that helped cause obesity.
The mutations were located in non-coding portions of FTO involved in regulating gene expression. But when Nóbrega looked closer, he found that something was amiss. These regulatory regions contained some elements that are specific for the lungs, one of the few tissues in which FTO is not expressed. “This made us pause,” he says. “Why are there regulatory elements that presumably regulate FTO in the tissue where it isn’t expressed?”
This was not the first red flag. Previous attempts to find a link between the presence of the obesity-associated mutations and the expression levels of FTO had been a “miserable failure”, he says. When Nóbrega presented his new results at meetings, he adds that many people came to him to say ‘I just knew there was something wrong here’.
So Nóbrega’s team cast the net wider, looking for genes in the broader neighbourhood of FTO whose expression matched that of the mutations, and found IRX3, a gene about half a million base pairs away. IRX3 encodes a transcription factor — a type of protein involved in regulating the expression of other genes — and is highly expressed in the brain, consistent with a role in regulating energy metabolism and eating behaviour.
When they examined the looping three-dimensional structure of the chromosome on which both genes sit in mice, zebrafish and human cells, they found that the obesity-associated regions in FTO were physically in contact with the promoter (the initial gene sequence which acts as an on/off switch) of IRX3. So the switches that turn on IRX3 are actually located far away from IRX3 itself, inside another gene. “We think of the genome as a linear thing, but it’s really a complex 3D structure that coils back onto itself,” he says.
IRX3 also appeared to be strongly linked with obesity. People with one of the obesity-associated mutations showed higher expression of IRX3, but not FTO, in brain tissue samples, the team found. Nóbrega and his colleagues also found that mice lacking the gene weighed 25–30% less than mice with a functional IRX3 gene; did not gain weight on a high-fat diet; were resistant to metabolic disorders such as diabetes and had more of the energy-burning cells known as brown fat. The same results were seen in mice in which the expression of IRX3 was blocked in the hypothalamus, a brain region known to regulate feeding behaviour and energy balance.
Inês Barroso, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, says that the work answers some of the questions around the biology of the link found in the genome-wide association studies (GWAS). “That’s always the tricky thing; a GWAS gives you an association, but it’s just a marker on the genome, it doesn’t actually say anything about which gene it’s affecting,” she says. “This strongly suggests that mediation of body mass is going to be through IRX3 rather than FTO.”
Nóbrega thinks geneticists should keep in mind this example of unexpected interactions between distant genes when dealing with genetic association studies. “There may be many other cases where people are studying the wrong gene,” he says. “We might be chasing ghosts.”
New genetic mutations shed light on schizophrenia
Researchers from the Broad Institute and several partnering institutions have taken a closer look at the human genome to learn more about the genetic underpinnings of schizophrenia. In two studies published this week in Nature (1, 2), scientists analyzed the exomes, or protein-coding regions, of people with schizophrenia and their healthy counterparts, pinpointing the sites of mutations and identifying patterns that reveal clues about the biology underlying the disorder.
When it comes to the rising prevalence of Type 2 diabetes, there are many factors to blame.
Diet and exercise sit somewhere at the top of the list. But the genes that some of us inherit from Mom and Dad also help determine whether we develop the disease, and how early it crops up.
Now an international team of scientists have identified mutations in a gene that suggests an explanation for why Latinos are almost twice as likely to develop Type 2 diabetes as Caucasians and African-Americans.
But here’s the kicker: You have to go further back on the family tree than your parents to find who’s to blame for this genetic link to diabetes. Think thousands of generations ago.
Harvard geneticist and his colleagues uncovered hints that humans picked up the diabetes mutations from Neanderthals, our ancient cousins who went extinct about 30,000 years ago.
"As far as I know, this is the first time a version of a gene from Neanderthal has been connected to a modern-day disease," Altshuler tells Shots. He and his colleagues the findings Wednesday in the journal Nature.
A few years ago, geneticists at the in Germany sent shock waves through the scientific community when they the genome of a Neanderthal from a fossil. Hidden in the genetic code were patterns that matched those in human DNA. And the data strongly suggested that humans were more than just friendly neighbors with Neanderthal.
"Now it’s well accepted that humans interbred with Neanderthals," Altshuler says. On average most of us carry about 2 percent of Neanderthal DNA in our genome. So it’s not surprising, he says, that 2 percent of our traits would be inherited from the ancient primates.
The new data don’t mean that Neanderthals had diabetes, Altshuler is quick to point out. “It just happens that this disease sequence came from them,” he says.
To identify genes that contribute to Latinos’ high rate of Type 2 diabetes, Altshuler and his team analyzed DNA from over 8,000 Mexicans and other Latinos.
The team found many genes already known to be involved with diabetes, such as one related to insulin production. But a new one also popped up in the analysis: a gene that’s likely involved in fat metabolism.
Mutations in this gene increase a person’s risk of getting Type 2 diabetes by about a 20 percent, Altshuler and the team found. If the person has two copies of the mutations, one from each parent, the risk rises by about 40 percent.
So for Mexican Americans, their for Type 2 diabetes goes from about 13 percent to 19 percent if they inherit two copies of the mutations. For other Americans, the risk gets boosted to about 11 percent from 8 percent.
"This is a genetic factor that has a modest affect on the risk of getting the disease. Not everybody that has it will have the disease," Altshuler says. "But the genes are very common in Latinos and Asians."
About half of Latinos carry the disease mutations, while 20 percent of Asians have it. On the other hand, only 2 percent of European Americans carry the mutations.
So the new genetic data help to explain a big chunk — perhaps almost a quarter — of the difference in Type 2 diabetes prevalence in Latinos versus European Americans.
"The findings are important because they give us a new biological clue about a gene involved in diabetes, which could lead to more treatments," Altshuler says. "The Neanderthal connection is interesting, but it’s not the essence of the work."
It was once thought that each cell in a person’s body possesses the same DNA code and that the particular way the genome is read imparts cell function and defines the individual. For many cell types in our bodies, however, that is an oversimplification. Studies of neuronal genomes published in the past decade have turned up extra or missing chromosomes, or pieces of DNA that can copy and paste themselves throughout the genomes.
The only way to know for sure that neurons from the same person harbor unique DNA is by profiling the genomes of single cells instead of bulk cell populations, the latter of which produce an average. Now, using single-cell sequencing, Salk Institute researchers and their collaborators have shown that the genomic structures of individual neurons differ from each other even more than expected. The findings were published November 1, 2013, in Science.
"Contrary to what we once thought, the genetic makeup of neurons in the brain aren’t identical, but are made up of a patchwork of DNA," says corresponding author Fred Gage, Salk’s Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease.
In the study, led by Mike McConnell, a former junior fellow in the Crick-Jacobs Center for Theoretical and Computational Biology at the Salk, researchers isolated about 100 neurons from three people posthumously. The scientists took a high-level view of the entire genome—looking for large deletions and duplications of DNA called copy number variations or CNVs—and found that as many as 41 percent of neurons had at least one unique, massive CNV that arose spontaneously, meaning it wasn’t passed down from a parent. The CNVs are spread throughout the genome, the team found.
The miniscule amount of DNA in a single cell has to be chemically amplified many times before it can be sequenced. This process is technically challenging, so the team spent a year ruling out potential sources of error in the process.
"A good bit of our study was doing control experiments to show that this is not an artifact," says Gage. "We had to do that because this was such a surprise—finding out that individual neurons in your brain have different DNA content."
The group found a similar amount of variability in CNVs within individual neurons derived from the skin cells of three healthy people. Scientists routinely use such induced pluripotent stem cells (iPSCs) to study living neurons in a culture dish. Because iPSCs are derived from single skin cells, one might expect their genomes to be the same.
"The surprising thing is that they’re not," says Gage. "There are quite a few unique deletions and amplifications in the genomes of neurons derived from one iPSC line."
Interestingly, the skin cells themselves are genetically different, though not nearly as much as the neurons. This finding, along with the fact that the neurons had unique CNVs, suggests that the genetic changes occur later in development and are not inherited from parents or passed to offspring.
It makes sense that neurons have more diverse genomes than skin cells do, says McConnell, who is now an assistant professor of biochemistry and molecular genetics at the University of Virginia School of Medicine in Charlottesville. “The thing about neurons is that, unlike skin cells, they don’t turn over, and they interact with each other,” he says. “They form these big complex circuits, where one cell that has CNVs that make it different can potentially have network-wide influence in a brain.”
Spontaneously occurring CNVs have also been linked to risk for brain disorders such as schizophrenia and autism, but those studies usually pool many blood cells. As a result, the CNVs uncovered in those studies affect many if not all cells, which suggests that they arise early in development.
The purpose of CNVs in the healthy brain is still unclear, but researchers have some ideas. The modifications might help people adapt to new surroundings encountered over a lifetime, or they might help us survive a massive viral infection. The scientists are working out ways to alter genomic variability in iPSC-derived neurons and challenge them in specific ways in the culture dish.
Cells with different genomes probably produce unique RNA and then proteins. However, for now, only one sequencing technology can be applied to a single cell.
"If and when more than one method can be applied to a cell, we will be able to see whether cells with different genomes have different transcriptomes (the collection of all the RNA in a cell) in predictable ways," says McConnell.
In addition, it will be necessary to sequence many more cells, and in particular, more cell types, notes corresponding author Ira Hall, an associate professor of biochemistry and molecular genetics at the University of Virginia. “There’s a lot more work to do to really understand to what level we think the things we’ve found are neuron-specific or associated with different parameters like age or genotype,” he says.
A collaborative formed by Autism Speaks, the world’s leading autism science and advocacy organization, has found full genome sequencing examining the entire DNA code of individuals with autism spectrum disorder (ASD) and their family members to provide the definitive look at the wide ranging genetic variations associated with ASD. The study published online today in American Journal of Human Genetics, reports on full genome sequencing on 32 unrelated Canadian individuals with autism and their families, participants in the Autism Speaks Autism Genetic Resource Exchange (AGRE). The results include both inherited as well as spontaneous or de novo, genetic alterations found in one half of the affected families sequenced.
This dramatic finding of genetic risk variants associated with clinical manifestation of ASD or accompanying symptoms in 50 percent of the participants tested is promising, as current diagnostic technology has only been able to determine a genetic basis in about 20 percent of individuals with ASD tested. The large proportion of families identified with genetic alterations of concern is in part due to the comprehensive and uniform ability to examine regions of the genome possible with whole genome sequencing missed in other lower resolution genome scanning approaches.
"From diagnosis to treatment to prevention, whole genome sequencing efforts like these hold the potential to fundamentally transform the future of medical care for people with autism," stated Autism Speaks Chief Science Officer and study co-author Robert Ring, Ph.D.
The study identified genetic variations associated with risk for ASD including de novo, X-linked and other inherited DNA lesions in four genes not previously recognized for ASD; nine genes previously determined to be associated with ASD risk; and eight candidate ASD risk genes. Some families had a combination of genes involved. In addition, risk alterations were found in genes associated with fragile X or related syndromes (CAPRIN1 and AFF2), social-cognitive deficits (VIP), epilepsy (SCN2A and KCNQ2) as well as NRXN1 and CHD7, which causes ASD-associated CHARGE syndrome.
“Whole genome sequencing offers the ultimate tool to advance the understanding of the genetic architecture of autism,” added lead author Dr. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at The Hospital for Sick Children (SickKids) and director of the McLaughlin Centre at the University of Toronto. “In the future, results from whole genome sequencing could highlight potential molecular targets for pharmacological intervention, and pave the way for individualized therapy in autism. It will also allow for earlier diagnosis of some forms of autism, particularly among siblings of children with autism where recurrence is approximately 18 per cent.”
This $1 million collaboration of Autism Speaks, SickKids, BGI and Duke University piloted Autism Speaks’ initiative to generate the world’s largest library of sequenced genomes of individuals with ASD announced in late 2011. “As we continue to test more individuals and their family members from the AGRE cohort, we expect to discover and study additional genetic variants associated with autism. This collaboration will accelerate basic and translational research in autism and related developmental disabilities,” concluded Autism Speaks Vice President for Scientific Affairs Andy Shih, Ph.D. who oversees the collaboration, “and this collection of sequenced genomes will facilitate new collaborations engaging researchers around the world, and enable public and private entities to pursue pivotal research.”
In this pilot effort, a total of 99 individuals were tested, including the 32 individuals with ASD (25 males and seven females) and their two parents, as well as three members of one control family not on the autism spectrum. Using families in the Autism Speaks AGRE collection, this Autism Speaks initiative will ultimately perform whole genome sequencing on more than 2,000 participating families who have two or more children on the autism spectrum. The data from the 10,000 AGRE participants will enable new research in the genomics of ASD, and significantly enhance the science and technology networks of Autism Speaks and its collaborators.
Using the study of genetic variation in a large panel of humans, chimpanzees, gorillas and orangutans, researchers from the Universitat Pompeu Fabra in Barcelona, Spain, and Washington University in Seattle have created a model of great ape history over the past 15 million years.
This is the most comprehensive catalog of great ape genetic diversity. The catalog elucidates the evolution and population histories of great apes from Africa and Indonesia. The research team hopes the catalog will also help current and future conservation efforts that strive to preserve natural genetic diversity in populations.
An international group of more than 75 scientists and wildlife conservationists worked on the genetic analysis of 79 wild and captive-born great apes. The group of great apes represents all six great ape species: chimpanzee, bonobo, Sumatran orangutan, Bornean orangutan, eastern gorilla and western lowland gorilla; as well as seven subspecies. The study, published in Nature, also included nine human genomes.
“The research provided us the deepest survey to date of great ape genetic diversity with evolutionary insights into the divergence and emergence of great-ape species,” noted Evan Eichler, a UW professor of genome sciences and a Howard Hughes Medical Institute Investigator.
Due to the difficulty in obtaining genetic specimens from wild apes, genetic variation among great apes had been largely uncharted prior to this study. The research team credits the many conservationists in various countries, many of them in dangerous or isolated locations, with the success of the project.
Peter H. Sudmant, a UW graduate student in genome sciences, said, “Gathering this data is critical to understanding differences between great ape species, and separating aspects of the genetic code that distinguish humans from other primates.”
Factors that shaped primate evolution, including natural selection, population growth and collapse, geographic isolation and migration, climate and geological changes are likely to be revealed by the analysis of great ape genetic diversity.
Understanding more about great ape genetic diversity, according to Sudmant, also contributes to knowledge about disease susceptibility among various primate species. This knowledge is important to both conservation efforts and to human health. For example, the ebola virus is responsible for thousands of chimp and gorilla deaths in Africa. Also, the origin of the HIV in humans comes from simian immunodeficiency virus (SIV), which is found in non-human primates.
“Because the way we think, communicate and act is what makes us distinctively human,” Sudmant, who works in a lab that studies both primate evolutionary biology and neuropsychiatric diseases such as autism, schizophrenia, developmental delay, and cognitive and behavioral disorders, said, “we are specifically looking for the genetic differences between humans and other great apes that might confer these traits.”
The differences between species may direct scientists to portions of the human genome associated with cognition, speech or behavior. This could provide clues to which mutations might underlie neurological disease.
The research team published a companion paper in Genome Research, in which they found the first genetic evidence of a disorder in chimpanzees that resembles Smith-Magenis syndrome. Smith-Magenis is a disabling physical, mental and behavioral condition in humans. The veterinary records of Suzie-A, the chimpanzee exhibiting the disorder, match human symptoms of Smith-Magenis almost exactly. Suzie-A was overweight, rage-prone, had a curved-spine and died from kidney failure.
The discovery of Suzie-A’s syndrome came about while the scientists were exploring and comparing the accumulation of copy number variants during great ape evolution, which are differences between individuals, populations or species in the number of times specific segments of DNA appear. The genomes of humans and great apes have been restructured by the duplication and deletion of DNA segments, which are also behind many genetic diseases.
The new catalog of genetic diversity will help address the challenging plight of great ape species on the brink of extinction, in addition to offering a view of the origins of humans and their disorders. It will also provide an important tool to allow biologists to identify the origin of great apes poached for their body parts or hunted for bush meat. The study also explains why current zoo breeding programs that have tried to increase the genetic diversity of their captive great ape populations have resulted in populations that are genetically dissimilar to their wild counterparts.
“By avoiding inbreeding to produce a diverse population, zoos and conservation groups may be entirely eroding genetic signals specific to certain populations in specific geographic locations in the wild,” Sudmant said.
Donald, one of the captive-bred apes studied by the team, had a genetic makeup of two distinct chimpanzee subspecies which are located around 1,250 miles away from each other in the wild.
The variety of changes that occurred along each of the ape lineages, as they separated from each other through migration, geological change and climate events, are delineated in the study findings. Natural disturbances such as the formation of rivers and the partition of islands from the mainland have all served to isolate groups of apes. These isolated populations are exposed to a unique set of environmental pressures that result in population fluctuations and adaptations, depending on the circumstances.
The ancestors of some present day apes were present at the same time as early human-like species. The researchers found, however, the evolutionary history of the ancestral great ape populations had far more complexity than that of humans. Human history appears “almost boring,” according to Sudmant and Eicher, when compared to our closest relatives, the chimpanzees. For example, the last few million years of chimp evolution are full of population explosions followed by implosions. These rapid fluctuations in chimpanzee populations demonstrate remarkable plasticity. Scientists still don’t understand the reasons for the fluctuations in chimpanzee population size long before our own population explosion.
Sudmant’s interest in studying and preserving the great apes stems from the similarities of the great apes to humans.
“If you look at a chimpanzee or a gorilla, those guys will look right back at you,” he said. “They act just like us. We need to find ways to protect these precious species from extinction.”