Genetic Variants Demonstrate Humans Continue To Evolve Through Natural Selection Interview with:

Hakhamanesh Mostafavi, MS PhD student Department of Chemical Engineering Columbia University

Mostafavi Hakhamanesh

Hakhamanesh Mostafavi, MS
PhD student
Department of Biological Sciences
Columbia University What is the background for this study?

Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection.

These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans.

In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets. What are the main findings?

Response: Across the genome, we found two common genetic variants with large effects on survival: (i) the ApoE4 variant, which is a major risk factor for late-onset Alzheimer’s disease, becomes less frequent among individuals older than 70, and (ii) a mutation in the CHRNA3 gene associated with heavy smoking, that affects survival in middle-aged men.

Most human traits are influenced by not one, but several, genetic variants; so we also looked at the joint effect of sets of genetic variants that contribute to a trait. We detected an association between longer life span and genetic variants that delay puberty timing and age at first birth. We also found a lower chance of survival for individuals genetically predisposed to higher cholesterol levels, body mass index, risk of coronary artery disease, and risk of asthma. What should clinicians and patients take away from your report?

Response: Natural selection is a gradual process, and even evolution of new features such as human bipedalism, involve small changes every generation, although they may take millions of years. With large enough datasets, which are now becoming available, we will be able to track small changes that happen over just a few generations, i.e., directly observe natural selection in action. What recommendations do you have for future research as a result of this study?

Response: It will be exciting to see approaches like ours applied to even larger datasets, and also looking at other components of evolutionary fitness such as fertility, to gain a comprehensive picture of what genetic variants influence fitness in humans and how. Thank you for your contribution to the community.


Identifying genetic variants that affect viability in large cohorts

Hakhamanesh Mostafavi , Tomaz Berisa, Felix R. Day,John R. B. Perry,Molly Przeworski ,Joseph K. Pickrell
PLOS Biology Published: September 5, 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.







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