Homo neanderthalensis: the Genome has Arrived

(Photograph used with permission by the copyright holder under GFDL.)

Four years ago I heard that a group of anthropologists had started on a project to sequence the Neanderthal genome. I was amazed. Many had their doubts and the researchers faced immense obstacles. Two years into the project, it had lost momentum and I accepted that the dream had failed.

Today I picked up this article from the journal Science: http://www.eva.mpg.de/neandertal/press/presskit-neandertal/pdf/Science_Green.pdf

More to come later. I needed to publish this immediately. Expect the world to change.

Later:

You may wonder why this is significant. Neanderthals and humans overlapped geographically and chronologically. They are our closest relatives in the fossil record and had similar lifestyles. However, humans were able to surpass Neanderthals in many aspects. Eventually, Neanderthals disappeared and only we remained. We do not completely understand what gave us the advantage over our non-human relatives, but studying the genome of this extinct species promises great insight into why.

Lets look at the article together.

The journal Science is unique in that it publishes studies from all disciplines of science and includes only those studies most important to the entire scientific community and also to the general public. The articles in this journal maintain high standards while modifying the standard format slightly to make the material accessible to non-specialist readers. The study by Green et al. that we will discuss mixes methods with discussion and conclusions instead of giving all of the methods in one sterile block, making it easier to follow.

We will start on page 715. The authors identify differences in protein structure that make humans different from Neanderthals. The first gene discussed, SPAG17, plays a role in  the flagellum of sperm, indicating that Homo sapiens sperm swim differently than that of H. neanderthalensis. Differences in PCD16 show that H. sapiens' wound healing process may differ from H. neanderthalensis. TTF1 is interesting because it helps regulate transcription of genes, meaning that it affects the way that all proteins are constructed from our DNA. This one gene has the potential to affect all other protein coding genes across the entire genome. Changes in RPTN indicate a difference in the epidermis, sweat glands, hair roots, and taste buds.

Also of note is TRPM1 that has lost functionality in some humans but is functional in Neanderthals. This gene codes for, in short, skin pigmentation.
The authors then focus on regions (called HARs) identified as being stable throughout the history of other vertebrates but that underwent many changes in H. sapiens. These areas should give clues about what makes us physiologically different from other animals, including H. neanderthalensis. Forty-five of these HARs were identified as being different in humans from the Neanderthal sequences. Not much is known about these regions, so the authors were unable to comment on them; however, they show great potential for further insights.

We skip to page 717. The authors investigate 20 regions in the human genome that have experienced heavy selective pressures relative to Neanderthals. The first five do not contain protein-coding genes and may be regulatory or structural in function. (Ask me about gene regulation and DNA structure and packaging if you are interested.) The most heavily selected on the remaining 15 regions contains the gene THADA, which has been associated with type II diabetes. This shows that human metabolism likely differs from Neanderthals. Other genes in these selected regions have been associated with diseases like Down syndrome, schizophrenia, and autism. Changes in these genes and regions would have created cognitive differences between the two species. The last gene discussed that has undergone heavy selection is RUNX2, which is responsible for the disease cleidocranial dysplasia. In short, this disease causes abnormal skeletal formations including an enlarged, protruding frontal bone (forehead or brow); heavy clavicles resulting in a change in the shoulder joint; and a bell-shaped rib cage. This one gene shows how some major skeletal features changed in humans.

The last half of the paper deals with multiple methods used to demonstrate the same results. The authors say it best:

"We find that the Neandertals are equally close to Europeans and East Asians.... However, the Neandertals are significantly closer to non-Africans than to Africans."

Multiple hypotheses can account for this, but the most likely scenario says that H. neanderthalensis interbred with H. sapiens some time during their overlapping histories but posterior to speciation. Because of this, a small percentage of Neanderthal DNA is present in the human population today.

The Neanderthal genome has initially created many more unanswered questions than those it has helped answer. The next few years (or couple of decades) will tell us much more of who Neanderthals were and what made the difference between our survival and their demise.