24 Oct Genes Beneficial To Our Ancestors, May Be Harmful Today
MedicalResearch.com Interview with:
Dr. Toomas Kivsild PhD
Department of Archaeology and Anthropology
University of Cambridge, Cambridge
Medical Research: What is the background for this study? What are the main findings?
Dr. Kivsild: Native populations of Siberia are known to have certain physiological
characteristics such as high basal metabolic
rate, and high blood pressure and low levels of serum lipids, that have
been explained as traits that have evolved
as a consequence of the adaptation of Siberians to their cold
environment. Genetic basis of cold adaptation is still poorly understood.
In our previous study using genome-wide genotyping scans we detected a 3
Mbp region of high haplotype homozygosity in chromosome 11 as a
candidate of strong positive selection in Northeast Siberians.
There were 79 protein coding genes mapping to this homozygosity region
but we could not determine which of the genes
was driving the signal we observed.
In this forthcoming paper we have used high coverage whole genome
sequences from 25 individuals from Northeast Siberia and we were able
to determine the most likely SNP that is responsible for the high
haplotype homozygosity in the chromosome 11 in Northeast Siberians maps
to CPT1A gene which is a key regulator of long-chain fatty-acid
oxidation in mitochondria. What makes this finding most interesting is
that the same SNP had previously been found in Greenland and Canadian
Inuits in association with high infant mortality and hypoketotic
hypoglycemia. There are only a few other similar cases, like the sickle
cell and APOL1 alleles, where disease associated genetic variants may
have risen to high frequency in modern day populations due to the
adaptive advantage they have presented in the past populations.
Medical Research: What should clinicians and patients take away from your report?
Dr. Kivsild: Evolutionary studies on genomic variation at population scale combined
with evidence from medical genetics may provide us with better
understanding of the causes of high frequencies of certain disease risk
alleles. This study highlights the environmental dependence of the
manifestation of such risks. The c.1436C>T mutation in the CPT1A gene
provides likely an advantage to its carriers to survive long journeys in
the Arctic environment in conditions when only high fat food sources are
available. On the other hand, in cases of starvation and disease,
however, the infants born homozygous for the mutation have lower chances
of survival.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Kivsild: Further work in model organisms, such as mice, is needed to determine
whether the adaptive benefits of this mutation are associated with the
lower rate of metabolism of fat (the so-called “slow-burner”,
sustainble use of fat energy hypothesis) or due to the employment of
alternative pathways to deploy the fat for the generation of heat rather
than ATP (cold adaptation hypothesis) or whether the adaptive role of
this mutation is associated with the restriction of the generation of
ketone bodies and brain energy supplies.
Citation:
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations
Clemente, Florian J. et al.
The American Journal of Human Genetics Available online 23 October 2014
Last Updated on October 24, 2014 by Marie Benz MD FAAD