The University of Arizona

UA Contributes to Largest Survey of Great Ape Genome Diversity

By University Communications and Institut de Biologia Evolutiva, July 3, 2013

UA researchers contributed to a new international study, which compiles the most comprehensive whole-genome sequencing of great ape populations to date. The study, published in Nature, provides new insights into human and great ape evolution over millions of years.

University of Arizona scientists contributed to a new study by an international team of researchers that has, for the first time, sequenced the genomes of a large number of great apes from across Africa and Southeast Asia.

The work, led by Evan Eichler of the University of Washington and Tomas Marques Bonet of Spain's Institut de Biologia Evolutiva, a partnership of the Universitat Pompeu Fabra and Consejo Superior de Investigaciones, focuses on characterizing natural variation in the genomes of the world's rapidly dwindling great ape populations.

Michael Hammer, a UA research scientist; Krishna Veeramah, a postdoctoral researcher in Hammer's lab; and other members of Hammer's lab team contributed genome sequence data and analyses of seven gorillas to the study, which included a total of 79 great apes.

The study is published in the journal Nature.

"This is the largest collection of whole genome sequences from great ape populations to date," Hammer said. "It's a landmark in that regard."

Great apes are a group of species made up of humans and our closest relatives: chimpanzees, gorillas and orangutans. These species all share a common ancestor from about 14-16 million years ago, but chimpanzees, for example, diverged from humans much more recently, about 6 million years ago.

Many of the populations surveyed for the study are highly endangered and may face extinction, Hammer explained, meaning this survey may be the largest that will ever be possible.

"This study supersedes many earlier studies of independent genetic regions by obtaining full genome sequence data from each individual," he added.

The Hammer Lab also performed analyses of the full dataset compiled by all institutions involved in the project.

"We analyzed across the board, not just the data we generated," Hammer said, adding that his team expects new insights to come from closer analysis of the genomic data in the future.

"It's just the beginning," he said. "It's like the broad brush-strokes that one would make from initial analyses of 80 genomes. What remains to be done is to get into the finer details – clearly we're going to identify many new questions to address."

The University of Washington's Peter Sudmant, co-lead author of the paper, said, "It's important to learn about the genetic diversity of great apes in order to put the history of our own genomes into context."

Recent advances in genome sequencing technologies have allowed researchers to learn an enormous amount about human genomes and genetic diversity by sequencing individuals of our own species.

In contrast, however, far less attention has been focused on our great ape relatives. This is largely due to the difficulty in obtaining DNA samples from these endangered species. Though many apes exist in captivity, these individuals are a poor reflection of wild diversity. The researchers instead tried to gather material from wild-born individuals working internationally with conservation groups and researchers.

The researchers found that human genomes show relatively little variation between each other in comparison to most great apes. Few ape species are as shallow as human when it comes to genetic diversity.

"This reduction in genetic diversity is commonly the result of an event called a population bottleneck," said Javier Prado-Martinez, a PhD student from Institut de Biologia Evolutiva and co-lead author of the study. "What's striking is how severe this bottleneck must have been in ancestral humans in comparison to most great apes."

The genomes of a pair of orangutans, for example, differ at more than two out of every 1,000 base-pairs, compared to one out of every 1,000 base-pairs between any two humans. A few species of great apes, however, were more similar to humans in that they showed a dearth of genetic variation; namely eastern lowland gorillas, western chimpanzees and bonobos. All of these species showed evidence of severe bottlenecks in their ancient history, possibly explaining the reduced genetic diversity.

The researchers focused particularly on comparing the evolutionary history of our closest relatives, chimpanzees, who are dispersed across Africa and classified into four major groups, or subspecies.

An open question among evolutionary biologists has been how these four populations relate to one another. By sequencing multiple individuals from each group, the researchers were able to resolve the phylogenetic relationship among these subspecies distinguishing two genetically distinct groups of chimps.

What also became apparent to the researchers was the complexity of the evolutionary history of chimps compared to humans. The patterns of genetic diversity were consistent with extensive gene flow or migration between ancestral populations with sudden expansions in population size followed by crashes.

In contrast, "humans have a relatively simple evolutionary history," Sudmant said. "It's clear that over the last few million years chimpanzee populations fluctuated enormously in size and complexity." The basis for these population collapses is unclear but does coincide, in part, with a period of time when human populations began to thrive.

A companion paper published in the journal Genome Research by Eichler and colleagues further explores how fluctuations in the size and complexity of ape populations affected a larger form for genetic variation, known as copy number variation. 

They found, in particular, that chimpanzees harbored an excess number of gene deletion events more than 2 million years ago, coinciding with genetic bottlenecks in ancient chimpanzee populations. These findings suggest that the chimpanzee lineage actually lost more genes early in its history when compared to the human branch.

The work is underscored by a sobering message, however. "We need to do more to protect these species and preserve their natural environment," Sudmant said. "Some great ape populations are quite literally on the brink of extinction and they are, more so than ever, at the mercy of our species."

Prado-Martinez expressed his hope that the resource would aid in conservation efforts. "Knowing more about the genomes of these species will help to inform field biologists on the origin of poached great apes and the better management of captive breeding programs."