A team of researchers led by computational biologist Liran Carmel and stem cell biologist Eran Meshorer, of the Hebrew University of Jerusalem’s Alexander Silberman Institute of Life Sciences has determined that modern-day homo sapiens and our ancient, extinct Neanderthal relatives differ by only a fraction of a percentage point.
Recent research suggests that Neanderthals may have evolved from Homo heidelbergensis — the last common ancestor they shared with humans — before splitting off from modern humans between 700,000 and 300,000 years ago. Neanderthals (Homo sapiens neanderthalensis) are a species of the genus Homo and a near-relative of our own species Homo sapiens, thought to have become extinct about 40,000 years ago.
The researchers examined differences in the epigenomes of humans and Neanderthals, as well as another ancient hominid species — the Denisovans. As opposed to the genome — the sequence of 3 billion molecules that constitute all of a person’s DNA — the epigenome bits of DNA that are turned on or off while the genome’s molecular sequence remains unchanged. It is the epigenome that can account for diverging traits in identical twins.
The researchers found that modern-day humans and our extinct Neanderthal cousins differ genetically by only a fraction of a percent. So what accounts for the differences ?
A new study published online in the journal Science reports the discovery of a cellular equivalent of on/off switches that determine which genes are activated or not.
Titled “Reconstructing the DNA Methylation Maps of the Neanderthal and the Denisovan,” (Science DOI: 10.1126/science.1250368), the Science paper is co-authored by Eran Meshorer, Liran Carmel, David Gokhman and Eitan Lavi of The Hebrew University of Jerusalem of the Department of Genetics Alexander Silberman Institute of Life Sciences; , Janet Kelso, Svante Paabo, and Kay Prufer of the Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, at Leipzig, Germany; Mario F. Fraga of the Cancer Epigenetics Laboratory, IUOPA, University of Oviedo and CNB-CSIC, Spain; and Jos A. Riancho of the Department of Medicine, Hospital U.M. Valdecilla, University of Cantabria at Santander, Spain.
The coauthors note that sequencing of Ancient DNA has recently provided high-coverage of archaic human genomes, but the evolution of epigenetic regulation along the human lineage remains largely unexplored.
The researchers reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing natural degradation processes of methylated and unmethylated cytosines, and by comparing these ancient methylation maps to those of present-day humans, they were able to identify some 2,200 differentially methylated regions (DMRs) around regions that were activated in today’s humans, but turned off in either or both of the ancient species, or vice versa. Ergo, differences between the three species could be attributed to on/off patterns in their respective DNA.
“Particularly,” they say, “we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species.”
An article by Ancient Origins’ April Holloway notes that one takeaway is that the scientists have shown that the genomes of Homo sapiens and Neanderthals are 99.84 percent genetically identical, have fewer than 100 proteins that differ in their amino acid sequence, and that 0.12 percent divergence accounts for fundamental distinctions stature and physique as well as disease susceptibility and neurological conditions found in humans but not Neanderthals.
There are of course other factors that pertain, including diet and environment, and from individual to individual, making it impossible to determine whether the distinct epigenomic on/off patterns found in Neanderthal genes are typical of the species overall or peculiar to the individual subject studied.
The Hebrew University of Jerusalem of the Department of Genetics Alexander Silberman Institute of Life Sciences