February 23, 2017 This visual abstract depicts the findings of McCoy et al., who show genome-wide interrogation of the functional differences between modern human and Neanderthal alleles reveals that Neanderthal-inherited sequences are not silent remnants of ancient interbreeding but have a measurable impact on gene expression that may contribute to phenotypic variation in modern humans. Credit: McCoy et al.\/Cell 2017 <\/p>\n
The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's function, or are they just silent passengers along for the ride? In Cell on February 23, researchers report evidence that Neanderthal DNA sequences still influence how genes are turned on or off in modern humans. Neanderthal genes' effects on gene expression likely contribute to traits such as height and susceptibility to schizophrenia or lupus, the researchers found. <\/p>\n
\"Even 50,000 years after the last human-Neanderthal mating, we can still see measurable impacts on gene expression,\" says geneticist and study co-author Joshua Akey of the University of Washington School of Medicine. \"And those variations in gene expression contribute to human phenotypic variation and disease susceptibility.\" <\/p>\n
Previous studies have found correlations between Neanderthal genes and traits such as fat metabolism, depression, and lupus risk. However, figuring out the mechanism behind the correlations has proved difficult. DNA can be extracted from fossils and sequenced, but RNA cannot. Without this source of information, scientists can't be sure exactly if Neanderthal genes functioned differently than their modern human counterparts. They can, however, look to gene expression in modern humans who possess Neanderthal ancestry. <\/p>\n
In this study, researchers analyzed RNA sequences in a dataset called the Genotype-Tissue Expression (GTEx) Project, looking for people who carried both Neanderthal and modern human versions of any given geneone version from each parent. For each such gene, the investigators then compared expression of the two alleles head-to-head in 52 different tissues. <\/p>\n
\"We find that for about 25% of all those sites that we tested, we can detect a difference in expression between the Neanderthal allele and the modern human allele,\" says the study's first author, UW postdoctoral researcher Rajiv McCoy. <\/p>\n
Expression of Neanderthal alleles tended to be especially low in the brain and the testes, suggesting that those tissues may have experienced more rapid evolution since we diverged from Neanderthals approximately 700,000 years ago. \"We can infer that maybe the greatest differences in gene regulation exist in the brain and testes between modern humans and Neanderthals,\" says Akey. <\/p>\n
One example uncovered by this study is a Neanderthal allele of a gene called ADAMTSL3 that decreases risk of schizophrenia, while also influencing height. \"Previous work by others had already suggested that this allele affects alternative splicing. Our results support this molecular model, while also revealing that the causal mutation was inherited from Neanderthals,\" says McCoy. Alternative splicing refers to a process in which mRNAs are modified before they leave the cell's nucleus. When the Neanderthal mutation is present, the cell's machinery removes a segment of the mRNA that is expressed in the modern human version. The cell ends up making a modified protein because of a single mutation from a Neanderthal ancestor. <\/p>\n
The connection between that modified protein, height, and schizophrenia still requires more investigation, but it's an example of how small differences between modern humans and Neanderthals can contribute to variation in people. <\/p>\n
\"Hybridization between modern humans and Neanderthals increased genomic complexity,\" explains Akey. \"Hybridization wasn't just something that happened 50,000 years ago that we don't have to worry about anymore. Those little bits and pieces, our Neanderthal relics, are influencing gene expression in pervasive and important ways.\" <\/p>\n
Next steps may include investigating whether Denisovansanother species of hominins that crossbred with modern humansare contributing to gene expression, as well as applying the side-by-side method of expression analysis more broadly. For this study, McCoy and his colleagues had to develop a new statistical approach to sift through the immense amount of RNA data, but the same technique could be used to compare gene expression differences between modern human alleles. <\/p>\n
Explore further: Long ago humans and Neanderthals Interbred: What happened to Neanderthal genes? <\/p>\n
More information: Cell, McCoy et al.: \"Impacts of Neanderthal-introgressed sequences on the landscape of human gene expression\" http:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(17)30128-9<\/a> , DOI: 10.1016\/j.cell.2017.01.038<\/p>\n Journal reference: Cell <\/p>\n Provided by: Cell Press <\/p>\n The Neanderthals disappeared about 30,000 years ago, but little pieces of them live on in the form of DNA sequences scattered through the modern human genome. A new study by geneticists at the University of California, Davis, ... <\/p>\n Although it's widely known that modern humans carry traces of Neanderthal DNA, a new international study led by researchers at the Stanford University School of Medicine suggests that Neanderthal Y-chromosome genes disappeared ... <\/p>\n If you can't seem to quit smoking, or have a tendency to become depressed, you might be able to blame your Neanderthal heritage. <\/p>\n (Phys.org)A team of researchers with members from the Max Planck Institute for Evolutionary Anthropology, Jena University Hospital and University College London has taken a very close look at the middle ear structure of ... <\/p>\n Neanderthals are thought to have disappeared in Europe approximately 39,00041,000 years ago but they have contributed 13% of the DNA of present-day people in Eurasia. Surprisingly, analyses of present-day genomes have ... <\/p>\n As the ancestors of modern humans made their way out of Africa to other parts of the world many thousands of years ago, they met up and in some cases had children with other forms of humans, including the Neanderthals and ... <\/p>\n The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's ... <\/p>\n In the middle of Alberta's boreal forest, a bird eats a wild chokecherry. During his scavenging, the bird is caught and eaten by a fox. The cherry seed, now inside the belly of the bird within the belly of fox, is transported ... <\/p>\n Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, ... <\/p>\n We all do it; we all need ithumans and animals alike. Sleep is an essential behavior shared by nearly all animals and disruption of this process is associated with an array of physiological and behavioral deficits. Although ... <\/p>\n Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support ... <\/p>\n A common roundworm widely studied for its developmental biology and neuroscience, also might be one of the most surprising examples of the eat-local movement. Princeton University researchers have found that the organisms ... <\/p>\n Please sign in to add a comment. Registration is free, and takes less than a minute. Read more <\/p>\n <\/p>\n See original here: February 23, 2017 This visual abstract depicts the findings of McCoy et al., who show genome-wide interrogation of the functional differences between modern human and Neanderthal alleles reveals that Neanderthal-inherited sequences are not silent remnants of ancient interbreeding but have a measurable impact on gene expression that may contribute to phenotypic variation in modern humans. Credit: McCoy et al.\/Cell 2017 The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's function, or are they just silent passengers along for the ride? Continue reading
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