Neanderthal genes: new data
Geneticists have explained the connection of schizophrenia with the Neanderthal heritage of man
Sofia Dolotovskaya, N+1
Researchers from The University of Washington has shown that sections of DNA that got into the genome of modern humans as a result of hybridization with Neanderthals still affect the expression of human genes. In particular, the DNA inherited from Neanderthals affects the manifestations of such signs as growth and the risk of developing schizophrenia. Article by McCoy et al. Impacts of Neanderthal-Introduced Sequences on the Landscape of Human Gene Expression is published in the journal Cell.
Early modern humans (Homo sapiens) after their migration from Africa to Eurasia (about 70 thousand years ago) mixed with other species of ancient humans, including Neanderthals and Denisovans. Neanderthals became extinct about 40,000 years ago, but about 2-3 percent of Neanderthal genes still remain in the genome of modern humans (not counting the indigenous inhabitants of Central and Southern Africa). Previous studies have shown that Neanderthal genes helped modern humans adapt to unusual conditions after migrating from Africa. In particular, Neanderthals passed on to modern humans genes encoding proteins that affect immunity and skin pigmentation.
Although scientists can trace exactly which fragments were transmitted to modern humans from Neanderthals, the question of whether the expression of Neanderthal gene variants differs from the genes of modern humans is still open. The reason for this is primarily that it is impossible to directly assess the expression of genes in Neanderthals themselves: RNA is preserved worse than DNA, and it cannot be isolated from the fossil remains of Neanderthals and sequenced.
In order to solve this problem, the authors of the new article found for their research people (a total of 214 people) heterozygous for Neanderthal gene variants – that is, people who have one allele of a gene "Neanderthal" and the other modern. For each allele of each of these genes, the researchers then analyzed the expression (using RNA analysis) in various parts of the body (in 52 tissues in total).
The researchers found about 5,000 "heterozygous" single nucleotide polymorphisms (differences in DNA sequences per nucleotide). Of these, approximately 25 percent were in genes in which expression differed between two alleles – Neanderthal and modern. A total of 767 such genes were found.
In general, there was no shift in the expression of Neanderthal alleles compared to "modern" ones: in half of the cases it was higher, and in half of the cases it was lower. However, differences were observed in different tissues: for example, the expression of Neanderthal alleles was especially low in the brain and testes. As the authors note, this is apparently due to the fact that these tissues have evolved faster than others since the separation of the Neanderthal and modern human lineages.
Schematic representation of the influence of Neanderthal DNA
on the expression of modern human genes (from an article in Cell).
Among the genes whose alleles differ in the level of expression, several genes were found whose Neanderthal variants increase the likelihood of various diseases – in particular, systemic lupus erythematosus (SLC15A4) and schizophrenia (ADAMTSL3). As it turned out, the expression of Neanderthal alleles of these genes is reduced compared to the expression of "modern" variants. This indicates that in the line of modern man, natural selection worked in favor of reducing the expression of "harmful" alleles.
Interestingly, variants of the ADAMTSL3 gene associated with the risk of schizophrenia are also associated with growth variability. Thus, Neanderthal variants of genes still continue to influence the phenotype (including appearance) of modern humans. At the same time, the Neanderthal allele, as previously shown, also directly affects the expression of the "modern" allele by regulating alternative splicing of the matrix RNA synthesized from it.
The detection of expression differences in the gene associated with the risk of schizophrenia is consistent with the recent discovery of traces of ancient positive selection in genes associated with Alzheimer's disease: according to the authors of the study, Alzheimer's disease has become humanity's payment for a developed brain.
Neanderthals lived in Europe, the Middle East and Central Asia from about 600 thousand years ago to 30-40 thousand years ago. There are various hypotheses about the cause of their extinction: perhaps they were mowed down by diseases brought by people from Africa, or climate changes during the last ice age and the inability to make warm clothes. Genetic studies indicate that the extinction of Neanderthals may be explained by their long-term low numbers: the bottleneck effect and the accumulation of harmful mutations led to a decrease in the fitness of the entire species.
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28.02.2017