“Neanderthal Man: In search of the lost genome" by Svante Pabbo

When I was a child, I was enchanted by the mysterious atmosphere of graveyards, hoping to see some skeletons, and know their lost stories. It seems I am not alone. Svante Pabbo, the Swedish molecular anthropologist is one of the most famous people to build a career on his childhood’s dream.

In a new memoir “Neanderthal Man: In search of the lostgenome", Svante Pabbo tells us a vivid story of how a curious and sentimental boy’s dream turns true. When he was a child, Svante Pabbo was attracted to Egyptian mummies and fascinated by their mysteries, hoping to solve the puzzles around the mummies one day. It was not until he was a graduate student that Svante Pabbo got the spark to analyze the genome of Egyptian mummies, when molecular biology started to boom in 1980s. Followed by a series of questions in 25 years, this initial maneuver led to his final success on sequencing the genome of Neanderthal man.

In the first chapter, Svante Pabbo described an eureka in 1996, when his student Matthias Krings decoded a fragment of the mitochondria DNA sequence from the DNA sample extracted from a 40000 years old Neanderthal Man that was excavated from the Neander Valley in Germany. He was so excited and cautious too that he did not open the champagne until he was confident with the results after several repeats. This breakthrough gave him confidence on decoding genes in ancient humans.

In the following chapters, Svante Pabbo tells his story in a chronological order, with logical questions step by step leading to the final answer. He first asked whether DNA could survive after tissue death. Answering this question, he heated the calf liver in the lab oven at 50 C for days, and got a few hundred nucleotides. Next, he asked how long the DNA could survive after tissue death. He obtained the samples of Egyptian mummies from East Germany through an anthropologist friend, and used nuclear dye to stain the cartilage and skin cells of the samples. After he found positive nuclear staining in these samples, he was sure the DNA is still there, he then extracted the DNA from these samples, and cloned the extraction into bacteria for sequencing. This experiment proved the preservation of DNA to as old as about 4000 years.

Contamination of modern DNA is the main concern of the whole business. Therefore, how to get rid of the contamination during the DNA extraction is the next question. Svante Pabbo and his students tried many ways to reduce the contamination to almost none, such as making a clean room with everything inside clean of DNA. They also developed some internal controls to solve this problem. Now the ancient DNA is cleared of contamination, they can continue to ask the next question: could 40000 years old Neanderthal man DNA be sequenced?

They first tried with a frozen Siberian mammoth about 50000 years old. If this works, the Neanderthal man will also work. They succeeded to get the mitochondrial DNA of this mammoth in 1994. Then they went on to extract DNA from Neanderthals. Now back to the scene in chapter one, they got lucky again and did get mitochondrial DNA of Neanderthals. Mitochondrial DNA has only a few hundreds nucleotides, whereas the nuclear genome has 6.4 billion nucleotides; thus, to see the big map of Neanderthal genome, they need to sequence the nuclear genome.

Most ancient DNA is degraded; therefore, it is not easy to get enough DNA to sequence nuclear DNA. Svante Pabbo examined Neandersal samples from several digging sites where the Neandersals were excavated. He could get very small amount of nuclear DNA from a few well-preserved Neandersal samples. Luckily, the DNA sequencing technology now makes it possible to use little DNA to sequence the whole genome. In 2010, Svante Pabbo and his group finally sequence the first Neandersal genome.

At last, the question comes to the human origin. Did Neandersals contribute DNA to modern human? Did modern human inbreed each other, and have gene flow to each other? By comparing the genomes of Neandersals with those of modern human of European, East Asian, African, American, and South Asian, Svente Pabbo found Neandersals shared more genetic variants with present-day humans in Europe than with present-day humans in Africa, and drew the conclusion that non-African modern human have 1-4% of their DNA originated from Neandersals 30000 years ago, when they met and inbred with each other in Middle East. After that short convention, Neandersals disappeared and modern human continued to migrate to the other part of the world and replaced the aboriginal ancient human.

Svante Pabbo’s writing is concise and logical; there is no jargon for laymen, and it is very easy to read.