Science Report 012

Decoding the Language of the Genome 06

What Do Chimps' Mutant Genes Say About Us?

Ayumu is an 18-year-old chimpanzee living in Japan who, much like his mother, works hard on any task given to him until he gets it done. He also has handsome looks that came from his father. But how do these traits relate to his genetic makeup? Which genes did Ayumu inherit from his father, and which ones from his mother? And how likely is it that Ayumu has mutate genes that weren’t present in his ancestors or even in his grandparents?

A group of Japanese scientists now have answers to all the questions. In a press conference at Kyoto University on Oct. 30, 2017, Dr. Tetsuro Matsuzawa from the Kyoto University Institute for Advanced Study(KUIAS), Dr. Asao Fujiyama from the National Institute of Genetics (NIG) and Dr. Yasuhiro Go, associate professor for the Center for Novel Science Initiatives at the National Institutes of Natural Sciences (NINS), announced that their research team had completed an “ultra-deep” whole genome sequencing study on Ayumu and his parents. The chimpanzee trio live at the Primate Research Institute of Kyoto University in Inuyama City in Aichi prefecture. The ultra-deep study, which analyzed an unprecedented number of DNA bases in the primate’s study history, revealed each offspring of the chimpanzee has estimated 1.48 newly-formed mutations per 100 million bases of DNA.

Dr. Matsuzawa and Dr. Fujiyama will explain what the results of the study on the chimpanzee family at Kyoto University’s Primate Research Institute say about chimpanzees’ closest cousin, the human, and the future of genome studies.

Click here for the press release.

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Ask an Expert:Dr. Tetsuro Matsuzawa

Dr. Tetsuro Matsuzawa serves as deputy director-general and distinguished professor at Kyoto University Institute for Advanced Study (KUIAS) with a joint appointment as professor for the university’s Primate Research Institute. In November 1977, three and a half years after receiving his bachelor’s degree in philosophy from Kyoto University in 1974, Dr. Matsuzawa founded a research project known as Ai Project to study the mind of the chimpanzee while also conducting surveys on the life of chimpanzees in the wild. He has used his research result to better understand human intelligence and behaviors as well as evolution, establishing a new academic field called comparative cognitive science.

Ask an Expert: Dr. Asao Fujiyama

Dr. Asao Fujiyama serves as the director of the Joint Support-Center for Data Science Research (DS) at the Research Organization of Information and Systems (ROIS) and as a specially-appointed professor for the National Institute of Genetics (NIG). He holds a Ph.D. in science from Nagoya University. He worked at the Faculty of Medicine at Osaka University, the Institute for Molecular and Cellular Biology at Osaka University, Cold Spring Harbor Laboratory and the University of Chicago before becoming assistant professor at the NIG in 1989, professor at the National Institute of Informatics in 2002 and professor at the NIG in 2008. He joined the DS as its director in 2016. He specializes in genomic bioscience and is known for comparative analysis of human and chimpanzee genomes.


Genomes, the Driver of Behaviors

The Primate Research Institute of Kyoto University, a worldly renowned primate research organization, is home to an extended chimpanzee family spanning three generations. Prof. Matsuzawa has been studying “the mind of the chimpanzee” since 1977 when he met Ai, a girl chimpanzee who had moved to the center earlier that year. Ai was estimated to be 23 years old when she gave birth to Ayumu on April 24, 2000. In his book, “Okāsan-ni natta Ai” (“Ai who became a mom”), Prof. Matsuzawa described the details of the labor, including how Ayumu’s dangling limbs had researchers concerned about his health at first.

“We have been conducting research on the learning behaviors of chimpanzees to find out how knowledge and experience accumulate to make their minds grow and change,” Prof. Matsuzawa said. “If I can use the iceberg metaphor, the tip is the behaviors, and the foundation that we cannot see under the sea is the genomes. Once we understand exactly how genes work, then the whole picture of the iceberg will begin to emerge more clearly,” he said. “For example, we already know that aggressive behaviors in chimpanzees have to do with a male hormone called Androgen and which genes function as Androgen receptors. This leads to our next question about which genes can help suppress aggressiveness and so on, and we can continue digging down into the matter this way.”

Prof. Tetsuro Matsuzawa (right) and Prof. Asao Fujiyama during an event at Kyoto University

Going Back 6 Million Years to Fill the Genetic Gaps

Humans and chimpanzees share so much of their DNA. This made Prof. Fujiyama decide to delve into the chimpanzee’s genome in the early 2000s while participating in a human genome project.

“By comparing the human genome to that of the chimpanzee that’s phylogenetically closest to us, we can figure out the genes that played the crucial roles in separating the two species from the common ancestor. And because most of the viruses that cause infections for chimpanzees also affect humans and vice versa, researchers are hopeful that studying chimpanzee genomes will help them develop effective treatments for human diseases,” Prof. Fujiyama said.

Prof. Fujiyama and fellow researchers have already conducted some ground-breaking research in the field, identifying mirroring relationships between the chimpanzee’s 22 chromosomes and the human’s 21 chromosomes and studying their commonalities and differences.

“Following our study in 2004, we concluded the human and the chimpanzee phylogenetically parted ways about 6 million years ago. We simulated the evolution on the premise that the generation time is 20 years and computed the rate of genetic mutation,” Prof. Fujiyama said.

Prof. Matsuzawa won’t forget the day Prof. Fujiyama visited him in Inuyama City to collaborate on that study in 2004.

“Ninety-nine out of 100 people who visit the Primate Research Institute look at the chimpanzees here and ask which one Ai is. Only Prof. Fujiyama asked, ‘Which one is Gon?’” Prof. Matsuzawa said, laughing. Gon is a root node of the Institute’s chimpanzee pedigree tree. “Prof. Fujiyama’s question showed that back in 2004, he already knew how to go about the chimpanzee genome study,” Prof. Matsuzawa said.

And, that’s how the ultra-deep whole genome sequencing of Ai, Ayumu and his father, Akira, began.

Taking the Guesswork out of Genomic Analysis

The whole genome sequencing on Ayumu and his parents was different from any genome studies conducted in the past on two fronts. First, the team ran a “personal genomics” study on the chimpanzee nuclear family, treating the parents-offspring trio as a set. Secondly, the team used the so-called next-generation sequencer to analyze 575, 463, and 468 giga bases of DNA – unprecedented numbers of reads for personal genomic sequencing of any mammalian species – in order to make the analysis highly accurate. Each chimpanzee has about 30 giga bases of DNA. The study also considered the actual generation time instead of an estimate used in the traditional phylogenetic research.

“From this research, we were able to determine the rate of germline newly formed mutations to be 1.48 mutations per 100 million bases,” said Prof. Go. “This is higher than the reported rate of 0.96 to 1.2 mutations per 100 million bases for humans. We also discovered 75 percent of the newly formed mutations for the chimpanzee originated with the paternal side (sperm).”

In other words, the team was able to pinpoint the types, the extent and frequency of errors in the transmission of genetic information from parents to an offspring.

“If we can go beyond the parents-and-son trio to cover more members of the second generation or even the third generation in the analysis, we will have a greater understanding of the inner workings of the chimpanzee’s genome,” Prof. Fujiyama said.

Tracing the Mammals’ Footsteps

For Prof. Matsuzawa, the next step in his research is to target non-primate mammals as study subjects. He is particularly interested in understanding the mind of the horse in connection with the genome at the bottom of the “iceberg.” He plans to conduct research both in laboratory settings and in the wild just as he’s done for his chimpanzee studies.

“The horse is a beloved animal, yet no one is studying the mind of the horse. It’s like a blind spot in our field,” Prof. Matsuzawa said.

He pointed out that studying mammals helps researchers better understand the primate and that the genome is the key to the big picture.

“Following the extinction of dinosaurs 66 million years ago, mammals adapted to the new environment and rapidly proliferated. Mammals are believed to have all come from a small, nocturnal creature resembling a mouse. This explains why many mammals are terrestrial,” Prof. Matsuzawa said. “In the meantime, the primate chose to live in the tree. As they began climbing trees, their four legs became four hands. Take a look at the four limbs of chimpanzees or Japanese macaques or whatever, and you will see they are hand-shaped. But the human is unique in that they decided to return to the ground from trees. We got our feet when we became humans,” he said. “When you think these things, you start to see the history of evolution. And, the genome is behind all of it.”

Prof. Matsuzawa believes the lack of research on the mind of the horse has to do with ‘Clever Hans,’ a horse that became famous for its claimed ability to perform math around the turn of the 20th Century,” Prof. Matsuzawa said. “A researcher eventually proved that it was all tricks. Little study has since been conducted to understand how the mind of the horse works, even though people have continuously used the ability of horses to take directions for horse races and other purposes.”

Interviewer: Rue Ikeya
Photographs: Yuji Iijima unless noted otherwise
The English version was prepared by Hiroko Sato based on the original story in Japanese.
Released on: July 10, 2018 (The Japanese version released on Sept. 11, 2017)

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