Talk by Choongwon Jeong
DAG Talk
- Date: Mar 8, 2016
- Time: 11:00 AM - 12:30 PM (Local Time Germany)
- Speaker: Choongwon Jeong
- The University of Chicago
- Location: MPI SHH Jena
- Room: Villa V14
- Host: Abteilung Archäogenetik
- Contact: arnold@shh.mpg.de
High altitude East Asians: genetic history and adaptations to altitude
High
altitude environments confer challenging burdens to their inhabitants,
driven by hypobaric hypoxia and other environmental factors.
However, indigenous populations of the Tibetan plateau, the most
prominent highland of the world, have thrived in such a harsh habitat
for millennia. Distinct physiological traits of Tibetans and Sherpa,
such as attenuated erythropoietic response to altitudinal
increase, have long been suspected to be based on adaptive genetic
changes. However, our understanding on their adaptations to the high
altitude, as well as their origin and population structure, is far from a
complete picture. In our lab, we have been studying
population genetics of Tibetans and Sherpa by generating and analyzing
array-based genotype data of 1,200 individuals and whole genome
sequences of several dozen, including ancient samples. We found
interesting features of Tibetans and Sherpa with regard to
their genetic history and adaptation. First, contemporary Tibetans from
the plateau harbor signatures of genetic admixture, best modeled by a
mixture of two ancestral gene pools represented by modern day Sherpa and
lowland East Asians. These two sources may
have a deep split time, beginning at 20-40 thousand years ago. Second,
sequencing of ancient samples from the high altitude corridors of the
Himalayan arc revealed continuous occupation of Tibetan-like populations
since the initial settlement, as well as in
situ evolution of adaptive haplotypes in the
EGLN1 and EPAS1 genes. Third, genomic scans of positive selection detected several interesting genes, such as
EGLN1,
EPAS1, SLCO1A2,
XYLT1, EP300 and
RUNX1. Last, we found several loci associated with key physiological
and fertility phenotypes in our Nepalese Tibetan cohort, including a
replication of association between lower hemoglobin level and the
adaptive
EPAS1 haplotype.
Interestingly, a phenotype-phenotype association was also found between
lower hemoglobin level and higher proportion of live births from
pregnancies, suggesting beneficial effect of low hemoglobin level.
To summarize, our study of high altitude East Asians show a role of
high altitude environments as a major determinant of genetic adaptation
and population structure of the inhabitants. Further study will help us
understand details of the genetic history of
Tibetans and their genetic basis of high altitude adaptations.