# Tracing the evolutionary history of human adaptive traits through ancient DNA

> **NIH NIH DP2** · YALE UNIVERSITY · 2024 · $1,507,500

## Abstract

PROJECT SUMMARY
As modern human expanded worldwide, they settled in different environments that subjected them
to selective pressure, driving genetic adaptations to varied local conditions. The origin of modern
adaptive variants is intricately intertwined with population history and local adaptations that shaped
the phenotypic diversity among human population today including health related traits. The
investigation of the functions of adaptive genetic variants provides important insights into the
mechanisms of human evolution and facilitate the identification of complex disease genes.
Nonetheless, current strategies for establishing connections between genetic variants and functions
face several limitations and new approach are needed. This proposal describes my plan to use
ancient human DNA to explore the origin of adaptive variants and the strength of selection that has
influenced their occurrences over time. Up to now, the use of ancient DNA (aDNA) to investigate
adaptation events was challenged by the scarcity of human fossils. To overcome this barrier, I
leverage on a new approach, I and others pioneered, to retrieve human aDNA from archaeological
sediment independent of skeletal remains. This breakthrough technology allows us to generate
genomic time-series data at a previously unachievable scale in any locations where human have
once lived. I will apply this innovative approach to investigate the evolution of recent human
phenotypes in East Asia. I propose to extract aDNA from a collection of sediment samples from the
Tsagaan Agui cave, an archaeological site in Mongolia with evidence of ancient human occupation
spanning the last 500,000 years. Mongolia, with its rich archaeological records is an ideal location
not only to retrieve aDNA from modern humans but also from now-extinct archaic humans that once
thrived in the region and were adapted to local environmental conditions hundreds of thousands of
years before the arrival of modern human. I will use target sequencing to infer the ancestry of past
individuals that occupied the site and genotype them across thousands of adaptive loci. By
combining these data to the archaeological and past ecological records of the region, I will
contextualize the emergence of specific adaptive variants in both archaic and modern humans. This
project will significantly enhance our understanding of past environmental conditions that contributed
to the acquisition of specific adaptive variants in modern human populations and holds the promise
of addressing fundamental queries about our evolutionary history by defining the genetic basis of
human adaptation to local environments, diets, and modern diseases.

## Key facts

- **NIH application ID:** 10909608
- **Project number:** 1DP2GM159182-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Diyendo Massilani
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,507,500
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909608

## Citation

> US National Institutes of Health, RePORTER application 10909608, Tracing the evolutionary history of human adaptive traits through ancient DNA (1DP2GM159182-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909608. Licensed CC0.

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