Most people know about Neanderthals from Charles Darwin’s The Origin of Species, but not a lot of people know that Darwin opposed the notion that Neanderthals were ancestors to humans. However, scientists recently discovered a genetic link between modern humans and Neanderthals.
Even though Neanderthals died nearly 40,000 years ago, most their genetic sequence is still present in modern humans though in small bits and pieces. Researchers haven’t’ been able to ascertain the effects of these genes until now.
Research evidence suggests that the genetic sequences of Neanderthals still determines the expression or silencing of genes in modern humans. They most likely affect the phenotypical expression of genes related to height, lupus or schizophrenia.
Scientists have known about the correlation between Neanderthal DNA and body processes like fat metabolism, predisposition to lupus and depression. However, determining the processes behind the relationship hasn’t been easy seeing that fossil DNA can be sequenced and RNA can’t.
This limitation makes determining whether Neanderthal DNA functioned differently than that of modern day humans. However, researchers can study gene expression in modern day humans of Neanderthal ancestry.
For the study, researchers used the GTEx project to analyze RNA sequences from individuals who possessed both modern human and Neanderthal alleles. They then analyzed each gene and compared the genetic expression of the inherited alleles side by side.
According to Rajiv McCoy, a postdoctoral researcher at UW and the first author of the study, there is a genetic expression variation between the modern human and Neanderthal allele in 25% of the gene loci. There is an especially low Neanderthal allele expression in the testes and brain which means that these tissues rapidly evolved after diverting from our Neanderthal ancestry nearly 700,000 years ago.
According to Akey, this leads us to conclude that the greatest gene regulation variation between Neanderthals and modern humans are in the brains and testes.
For instance, researchers uncovered ADAMTSL3 is a Neanderthal allele which reduces the risk of developing schizophrenia but also affects height. Previous research studies suggested that ADAMTSL3 affected alternative gene splicing and the results of the study further supported this molecular model.
Additionally, the study revealed that casual mutation was a consequence of inherited Neanderthal DNA. In Neanderthal mutation, the cell’s replication machinery excises a portion of the m-RNA in modern humans which leads to the formation of a modified protein. The correlation between the modified protein and the phenotypical expression of height and schizophrenia still require further investigation.
With that said, this goes to show how minute differences between Neanderthals and modern humans influence genetic and phenotypical variations in people. Akey further states that the increased genetic complexity was as a consequence of the hybridization between Neanderthals and modern humans and isn’t just something that occurred 50,000 years ago.
The tiny bits and pieces of Neanderthal DNA significantly contribute to genetic expression in ubiquitous and far-reaching ways. The next step for the researchers is to assess whether Denisovans influence gene expression as well as using the head-to-head expression analysis technique in a broader perspective.
For this research study, McCoy and his team had to develop a novel statistical approach for sifting through large amounts of RNA, but the same method could be applied in comparing gene expression variations in alleles found in modern humans.