The topic for these GEITP pages today — is mind-boggling; I had no idea something like this was remotely yet possible. Recall that any trait (e.g. type-2 diabetes, coronary heart disease, height, body mass index, response to a drug or environmental toxicants) — reflects contributions of genetics, epigenetic effects, environmental factors, endogenous influences and our individual microbiome. Recall further that epigenetic effects include DNA-methylation, regulation by microRNAs, histone modifications, and chromatin remodeling; and that we have assays for the first two processes, while we’re still trying to understand better the latter two processes. Throughout life, epigenetic modifications of DNA have a profound influence on most biological traits (epigenetic effects are what help determine differences between cells having otherwise identical genomes). One of the best-studied epigenetic changes [see attached article and editorial] is DNA-methylation — which means the addition to a DNA base of a methyl chemical group, the result of which is to slow down or extinguish activity of a gene.
During the past decade, researchers have mapped methylation patterns across the genomes of fossil DNA from Neanderthals and Denisovans, and identified a limb-development gene for which these patterns differed between the extinct groups and modern
humans (e.g. see Science 2014; 344: 523–527). In the present study [see attached], authors have compared methylation patterns of Neanderthals and Denisovans with databases of epigenetic modifications in human tissue — in which the impacts on gene expression are known — and produced a list of hundreds of genes for which expression levels probably differed between archaic hominids and modern humans. To connect this list to anatomical traits, authors looked at another database, which catalogs the physical effects of genetic mutations in humans having rare anatomical-trait disorders; authors reasoned that diminished gene expression, caused by DNA methylation, was roughly analogous to the effects of these human disease-causing mutations [!!!!].
Before applying this method to Denisovans, authors first tested whether it could successfully predict the facial anatomy of Neanderthals (facial anatomy of Neaderthals is well known from looking at DNA of hundreds of fossils). Authors found 33 Neanderthal
traits that could potentially be predicted from DNA-methylation patterns; their results accurately predicted 29 of those traits [e.g. Neanderthals have broader faces and flatter heads than (most of us) modern humans]. Authors suggest that Denisovans likely shared with Neanderthals — traits such as an elongated face and a wide pelvis. Authors also identified specific Denisovan-derived changes, (i.e. higher dental arch and lateral cranial expansion). See the amazing reconstructed face of a young female Denisovan — based on skeletal traits derived from her ancient DNA [in the attached editorial]. Authors conclude that DNA-methylation patterns can be used to aid in reconstructing anatomical features, including some traits that have not “survived” to be seen today in modern humans. 😊
· Cell Sept 2019; 179: 180-192 & editorial Nature Sept 2019; 573: 475-476