Immune properties in ancient DNA found in isolated villages might
benefit humanity today
Genetic diversity among hunter-gathers of Indonesia, including last significant vestige of DNA from extinct human cousins

Date:
June 15, 2020
Source:
The Translational Genomics Research Institute
Summary:
Could remnants of DNA from a now extinct human subspecies known as
the Denisovans help boost the immune functions of modern humans? An
international study represents the first characterizations of
genes in the DNA of healthy individuals from geographically and
genetically distinct populations in Indonesia.



FULL STORY ========================================================================== Could remnants of DNA from a now extinct human subspecies known as the Denisovans help boost the immune functions of modern humans?

==========================================================================
An international study co-led by the Translational Genomics Research
Institute (TGen), an affiliate of City of Hope, and published in the
scientific journal PLOS Genetics, represents the first characterizations
of genes in the DNA of healthy individuals from geographically and
genetically distinct populations in Indonesia.

Scientists studied genomic diversity among 116 individuals from three Indonesian populations: the Mentawai on the west coast of Sumatra; the
Sumba in central Indonesia; and the Korowai, a group of hunter-gatherers
from the western side of the isle of New Guinea.

The Korowai are of particular interest, as their DNA holds the world's
last remaining significant remnants of genetic code -- as much as 5% --
from a cousin of modern humans called the Denisovans, the study says. Like
the better- known Neanderthals of Europe, the Denisovans of Asia also
are an extinct human subspecies who lived tens of thousands of years
ago. And just as Neanderthals passed on certain immune properties to
those of European ancestry, the Denisovans may have passed on protective
immune genes to their southeast Asian decedents.

"Genome sequencing efforts have mainly focused on populations of
European descent," said Dr. Heini Natri, a TGen postdoctoral fellow
and one of the lead authors of the study. "Most of the world is deeply understudied. As we move further into the age of personalized and genomic medicine, understanding how genetics drives disease-risk across diverse populations is crucially important." Why study Indonesia? Spread across
more than 17,000 islands between mainland Asia and Australia, Indonesia
is the world's largest archipelago. Geographically as large as the
U.S. or Europe, Indonesia's 273 million inhabitants make it the world's
fourth most populous nation, after China, India and the U.S. And yet,
Indonesia has been largely excluded from the genomics sequencing boom of
the past decade, and there previously have been no analyses of diversity
in gene regulation in either Indonesia or the other island nations of
southeast Asia.



========================================================================== "This lack of information from Indonesia is alarming as it is an epicenter
of infectious disease diversity, such as malaria and other emerging
tropical diseases," Dr. Natri said. "Immune pressure from infectious
diseases are responsible for some of the strongest selective forces
on humans throughout our species' evolutionary history, and Indonesia
offers unique advantages for studying responses to these diseases."
Because of Indonesia's island environment, its many isolated villages
and the relatively low population density on most of its nearly 6,000
inhabited islands, the study suggests there is low genetic diversity
among those who live on each island, and even in each village, but also
high genetic diversity among people from island to island, "making it a
near unique study system for examining gene-by-environment interactions,"
the study said.

Scientists focus on immune properties of ancient human DNA Dr. Nicholas Banovich, an Assistant Professor in TGen's Integrated Cancer Genomics
Division, a human geneticist, and a senior author of this PLOS Genetics
paper, said the study's results highlight genes involved in the function
of immune cells. This suggests a potentially adaptive response to local environmental pressures, including pressures from various tropical
diseases.

"One of the unique aspects of Indonesia is individuals on the island of
New Guinea have high remnants of DNA from one of our extinct ancestors,
the Denisovans," Dr. Banovich said. "We found these remnants of ancient
DNA are driving changes in genes involved in immune function. This
study demonstrates the power of including understudied populations in
an effort to increase the overall understanding of human genetics."
The international team is continuing its study, integrating more genetic
data, exploring patterns of local ancestry and how archaic human genes
are imbedded in modern-day populations.

"We are now attempting to pinpoint individual genetic changes -- in
particular, those that are carried over in these remnant DNA fragments
from Denisovans - - which regulate how much or how little a gene is
turned on, and how these genetic changes may shape immune response,"
Dr. Natri said.


========================================================================== Story Source: Materials provided by The_Translational_Genomics_Research_Institute. Original written by Steve Yozwiak. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Heini M. Natri, Katalina S. Bobowik, Pradiptajati Kusuma, Chelzie
Crenna
Darusallam, Guy S. Jacobs, Georgi Hudjashov, J. Stephen Lansing,
Herawati Sudoyo, Nicholas E. Banovich, Murray P. Cox, Irene
Gallego Romero.

Genome-wide DNA methylation and gene expression patterns reflect
genetic ancestry and environmental differences across the Indonesian
archipelago.

PLOS Genetics, 2020; 16 (5): e1008749 DOI:
10.1371/journal.pgen.1008749 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200615140838.htm

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