# Neanderthal Gene Variants and Their Impact on Medication Response
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Chapter 1: The Legacy of Neanderthals
The existence of a single human species currently inhabiting our planet is quite unique. Throughout most of our evolutionary journey, multiple human species coexisted, often interbreeding and producing hybrids. In regions like Europe and Southwest Asia, Neanderthals were our closest relatives until their extinction approximately 40,000 years ago, though this timeline remains a topic of discussion. Recent studies have revealed that these resilient beings were not merely primitive cave dwellers; they were skilled hunters, competent cooks, artisans in jewelry-making, and possibly even musicians. Their capabilities suggest they likely communicated with a complexity beyond mere grunts.
Despite their numerous strengths, Neanderthals eventually vanished from the Earth. While the specific reasons for their extinction remain unclear, it likely resulted from a combination of factors, including environmental changes, diseases, and competition with Homo sapiens. Nonetheless, remnants of their existence persist in our DNA.
Research has illuminated the genetic distinctions between contemporary humans and Neanderthals, revealing that some genetic variants originating from Neanderthals have been passed down to modern human populations due to interbreeding.
The first video, "Svante Pääbo: DNA clues to our inner Neanderthal," delves into the genetic influences that Neanderthals have left on modern humans, providing insights into how these ancient genes affect us today.
Section 1.1: The Significance of Gene Variants
The relevance of these inherited gene variants cannot be understated. Research has connected sequences of ancient Neanderthal DNA found in modern individuals to various health risks, including depression, blood clotting disorders, diabetes, immune response variations, and even physical traits like eye color and skull shape. While the impact of these links is generally minor, more recent analyses indicate that a few specific characteristics in modern humans are notably influenced by Neanderthal DNA, particularly in areas such as blood clotting, height, and the likelihood of developing prostate cancer.
Subsection 1.1.1: New Discoveries in Drug Metabolism
A recent study has introduced another dimension to this conversation: how Neanderthal gene variants affect our metabolism of certain medications, such as warfarin (used to prevent blood clots) and phenytoin (used to manage seizures). Researchers analyzed genetic data from over 2,500 individuals of various ethnic backgrounds, as part of the 1,000 Genomes Project. They identified two specific variant alleles (CYP2C9*2 and CYP2C8*3) that trace back to Neanderthal ancestry. These alleles reside on the same chromosome (chromosome 10) and are frequently inherited together due to their close proximity, a phenomenon known as linkage disequilibrium.
Section 1.2: The Role of Cytochrome P450 Enzymes
The intriguing aspect of these alleles is that they are variants of genes coding for cytochrome P450 enzymes (CYPs), which play a crucial role in drug metabolism by oxidizing various compounds and facilitating their elimination from the body. Specifically, CYP2C8*3 is associated with an increased metabolism of some medications, like pioglitazone, while decreasing the metabolism of R-ibuprofen. In contrast, CYP2C9*2 leads to diminished enzyme activity, resulting in slower drug metabolism.
The combination of these two Neanderthal-derived alleles is linked to significant alterations in the metabolism of several medications, particularly leading to reduced breakdown of warfarin and phenytoin, which can cause toxic effects at otherwise safe doses.
The second video, "Public Lecture by Prof. Svante Pääbo at Aim Universe Tedako Hall (2022 Nobel Laureate)," provides further insights into the impact of Neanderthal genetics on human health and medicine.
Chapter 2: Conclusion
In conclusion, the influence of Neanderthal gene variants on modern human health is a fascinating area of study that highlights our complex evolutionary history. While the Neanderthals may no longer walk the Earth, their genetic legacy continues to shape our biology in significant ways. Thank you for reading, and I invite you to check out my newsletter, Thinking Ahead, where I explore broader themes in science, philosophy, and technology. Your interest would be greatly appreciated.