Researchers Create 15-Million-Year Model Of Great Ape History

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.”

New stroke gene discovery could lead to tailored treatments

A study led by King’s College London has identified a new genetic variant associated with stroke. By exploring the genetic variants linked with blood clotting – a process that can lead to a stroke – scientists have discovered a gene which is associated with large vessel and cardioembolic stroke but has no connection to small vessel stroke.

Published in the journal Annals of Neurology, the study provides a potential new target for treatment and highlights genetic differences between different types of stroke, demonstrating the need for tailored treatments.

Approximately 152,000 people in Britain have a stroke each year, costing the UK over £8.2 billion. While there are thought to be 1.2 million stroke survivors in the UK, more than half have been left with disabilities that affect their daily lives.

A stroke occurs when the blood supply to the brain is cut off, often due to a blood clot blocking an artery that carries blood to the brain, which then leads to brain cell damage. Coagulation (blood clotting) abnormalities, particularly easy clotting of the blood, are therefore common contributing factors in the development of stroke.

Dr Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s and lead author of the paper, said: ‘Previous studies have demonstrated the influence of genetic factors on the components of coagulation. The goal of this study was to extend these observations to determine if they were further associated with different types of stroke.’

The research was carried out in three stages. The first consisted of a genome-wide association study (GWAS) in 2100 healthy volunteers which identified 23 independent genetic variants that were involved in coagulation. The second stage examined the 23 variants in 4200 stroke and non-stroke cases from centres across Europe (Wellcome Trust Case Control Consortium 2 and MORGAM collections) and found that a particular mutation on the ABO gene was significantly associated with stroke.

Stage three of the study used the MetaStroke cohort, a project of the International Stroke Genetics Consortium which comprises 8900 stroke cases recruited from centres in the Europe, USA and Australia, whose DNA has been collected and undergone GWA scan. It was confirmed that a variant in the ABO blood type gene was associated with stroke, a finding specific to large vessel and cardioembolic stroke.

Dr Williams said: ‘The discovery of the association between this genetic variant and stroke identifies a new target for potential treatments, which could help to reduce the risk of stroke in the future. It is also significant that no association was found with small vessel disease, as this suggests that stroke subtypes involve different genetic mechanisms which emphasises the need for individualised treatment.’