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Developmental Biology - Genetics

Digging Up Ancient Gene Signals In Modern Humans

With new genome analysis tools, scientists have a new understanding of how modern humans made their ancient migrations...


With new genome analysis tools, scientists have made significant advances in understanding modern humans' origins and ancient migrations. But trying to find ancient DNA, let alone prove such ancient DNA is ancestral to a living population today, is extremely challenging.

A new study in Molecular Biology and Evolution (MBE) is adding to our understanding. Researchers are reconstructing artificial genomes from detailed examination of elements from 565 contemporary South Asians, in order to extract ancient signals that recapitulate the long history of human migration and admixture in that region.
"All in all, our results provide a proof-of-principle for the feasibility of retrieving ancient genetic signals from contemporary human subjects, as if they were genomes from the past embedded in amber."

Luca Pagani PhD, Research Coordinator of the study.

The study was led by Burak Yelmen and Mayukh Mondal from the Institute of Genomics of the University of Tartu, Estonia and coordinated by Luca Pagani from the same institution and from the University of Padova, Italy.
"The genetic components we managed to extract from modern genomes are invaluable, given the shortage of ancient DNA available from South Asian human remains. They allow us to explain the genetic composition of ancient populations that inhabited the area."

Burak Yelmen PhD, Institute of Genomics, University of Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Estonia and co-first author.

While studying the mixing events that brought ancient human populations to form contemporary South Asians, researchers noted that some portion of the genomes had not mixed as expected — as if genetic variants which evolved in South Asia, or the ones that arrived from West Eurasia, were important for adaptation to the local lifestyle through admixture.

"Among these variants, we found genes important for immunity and for dietary changes, as one may expect for human populations adapting to new sets of pathogens or food. Intriguingly, we also noted genetic variants implicated in skin pigmentation of West Eurasians, were under opposite selective forces. Some highly frequent, others almost lost after admixture events. Skin pigmentation is a fascinating and complex subject. We are still trying to understand what, if any, would be the adaptive implications of the signal we detected," explains Mayukh Mondal PhD, the Institute of Genomics, University of Tartu, Estonia, and joint first author.
The evolution of skin pigmentation revealed many genetic variants for the population studied. This will add to the growing picture of the diversity of South Asians, and add to future studies of the origins of our modern human population.

According to Mayukh Mondal: "These signals can complement the picture emerging from the booming field of ancient DNA by providing high quality genomic sequences especially for areas of the world where archaeological human remains are scarce or poorly preserved."

Abstract
Genetic variation in contemporary South Asian populations follows a northwest to southeast decreasing cline of shared West Eurasian ancestry. A growing body of ancient DNA evidence is being used to build increasingly more realistic models of demographic changes in the last few thousand years. Through high quality modern genomes, these models can be tested for gene and genome level deviations. Using local ancestry deconvolution and masking, we reconstructed population-specific surrogates of the two main ancestral components for more than 500 samples from 25 South Asian populations, and showed our approach to be robust via coalescent simulations.

Our f3 and f4 statistics based estimates reveal that the reconstructed haplotypes are good proxies for the source populations that admixed in the area and point to complex inter-population relationships within the West Eurasian component, compatible with multiple waves of arrival, as opposed to a simpler one wave scenario. Our approach also provides reliable local haplotypes for future downstream analyses. As one such example, the local ancestry deconvolution in South Asians reveals opposite selective pressures on two pigmentation genes (SLC45A2 and SLC24A5) that are common or fixed in West Eurasians, suggesting post-admixture purifying and positive selection signals, respectively.

Authors
Burak Yelmen, Mayukh Mondal, Davide Marnetto, Ajai K. Pathak, Francesco Montinaro, Irene Gallego Romero, Toomas Kivisild, Mait Metspalu and Luca Pagani.


Acknowledgements
The opportunity to contrast children's tissues at a single-cell level across ages would provide a unique and unprecedented window into pediatric diseases and their treatment. The PCA represents a project with challenges in tissue procurement and single-cell preparation but offers significant rewards in the potential contributions to our understanding of children’s health and disease. As a diverse and interdisciplinary effort, the PCA would benefit from programs such as the NIH Common Fund or the recently formed trans-NIH Pediatric Research Consortium (N-PeRC), which was founded to coordinate pediatric research programs across NIH’s 27 institutes and centers. It is expected that some fundraising efforts will often be specific to participating institutions or groups and not PCA-wide, as has been the case across the HCA.

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu


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Apr 8 2019   Fetal Timeline   Maternal Timeline   News  




Researchers reconstructed artificial genomes based upon analysis of genes from 565 contemporary
South Asian genomes. The genes extracted gave evidence of a long history of human migration
and admixture. Map: Wikipedia.


Phospholid by Wikipedia