Since 2010, researchers have established that between 1 and 4 percent of the DNA of people with Eurasian ancestry comes from Neanderthals. The findings sparked several hypotheses about how these genetic variations may affect modern humans’ behavior or physical characteristics, including everything from skin color to increased allergies to fat metabolism.

A recent study published in The Pharmacogenomics Journal shows that people who share specific genes with one of our closest hominin cousins, the Neanderthal, could find this balancing act a little more challenging.
The researchers found that breaking down pharmaceuticals such as ibuprofen, warfarin, and cholesterol-lowering statins is due to the enzymes’ variations. The discovery of these enzymes, which have such ancient roots, may help to explain why not every person reacts the same way to a given treatment.
“This is one instance in the medical setting where the Neanderthal admixture (occurs when previously diverged or isolated genetic lineages mix) has a noticeable effect. For those who carry the Neanderthal gene variant, therapeutic doses could otherwise be toxic,” says the study’s principal investigator, Hugo Zeberg, an evolutionary geneticist from the Karolinska Institute in Sweden, who is the study’s principal investigator.
The extent to which our immediate ancestors, who wandered the world for tens of thousands of years plus, stopped along the way to raise families with other migrants has been revealed by advances in genetic sequencing.
Though the genetic legacy left behind from this intermingling is still not fully understood year after year, researchers are gradually gaining insight into how genes that arose in extinct populations may be responsible for variations in our biology.
These changes could, in many cases, be relatively minor. But it can be crucial to understand as much as we can about an enzyme’s or protein channel’s evolutionary history regarding how it influences human health.
CYP2C9

CYP2C9 is a gene that encodes the cytochrome P450. It is a super-family of liver enzymes responsible for breaking down various drugs humans frequently take to treat everything from inflammation to epilepsy. It also happens to have a range of slightly different forms, each resulting from a different way to code CYP2C9. Of course, some structural differences are better than others at metabolizing medications. It means that how long your dose of medicine sticks around in your body depends on the CYP2C9 variant you inherit.
CYP2C9*2
CYP2C9*2 is a variety of CYP2C9. It is 70 percent less active compared to the more common CYP2C9*1 gene variant. This suggests that some medications may be metabolized more slowly by CYP2C9*2 carriers. CYP2C9*2 frequently appears, especially in members of other variants classed as CYP2C8*3. This wouldn’t seem strange if they weren’t separated by tens of thousands of DNA bases.
Gene comparison
Knowing that paired gene variations widely spaced on our chromosomes often have their origins in Neanderthal genomes, Zeberg and his team compared the sequences from 146 families to see the extent of variation from similar stretches of code in genetic databases representing other modern and ancestral populations.
Findings
They discovered the stretch of DNA containing the two cytochrome gene variants responsible for encoding the P450 cytochrome was sufficiently similar to the Neanderthal’s version to indicate that the two genes were almost certainly passed on during the mixing of our family lines tens of thousands of years ago.

The researchers, however, caution that this finding could not significantly impact how we manage patients using drugs like statins or warfarin. Experts already keep a close eye on how we handle picky medications, frequently checking blood levels to ensure dosages are within acceptable ranges.
Researchers conclusion
Tracing the variant ancestry in such significant enzymes may help us better understand the environment in which they evolved. Although, adding context that helps us understand the diversity of health in individuals we see today.
Feature image credit: Homo sapiens neanderthalensis-Jäger by Neanderthal-Museum, Mettmann under CC BY-SA 4.0