Ancient Ancestry Informative Markers for Identifying Fine-Scale Ancient Population Structure in Eurasians.

Umberto Esposito,Mehdi Pirooznia,Ranajit Das,Eran Elhaik,Syakir Syed

doi:10.3390/genes9120625

Abstract

The rapid accumulation of ancient human genomes from various areas and time periods potentially enables the expansion of studies of biodiversity, biogeography, forensics, population history, and epidemiology into past populations. However, most ancient DNA (aDNA) data were generated through microarrays designed for modern-day populations, which are known to misrepresent the population structure. Past studies addressed these problems by using ancestry informative markers (AIMs). It is, however, unclear whether AIMs derived from contemporary human genomes can capture ancient population structures, and whether AIM-finding methods are applicable to aDNA. Further the high missingness rates in ancient—and oftentimes haploid—DNA can also distort the population structure. Here, we define ancient AIMs (aAIMs) and develop a framework to evaluate established and novel AIM-finding methods in identifying the most informative markers. We show that aAIMs identified by a novel principal component analysis (PCA)-based method outperform all of the competing methods in classifying ancient individuals into populations and identifying admixed individuals. In some cases, predictions made using the aAIMs were more accurate than those made with a complete marker set. We discuss the features of the ancient Eurasian population structure and strategies to identify aAIMs. This work informs the design of single nucleotide polymorphism (SNP) microarrays and the interpretation of aDNA results, which enables a population-wide testing of primordialist theories.

Highlights

IntroductionGenomic techniques have been reshaping our fundamental understanding of human prehistory and origins [1]
We constructed a dataset of 150,278 autosomal single nucleotide polymorphism (SNP) from 302 ancient genomes classified into 21 populations from Europe, the Middle East, and North Eurasia, and dated to time periods spanning from 14,000 years ago through to 1500 years ago (Figure 3, Table S1)
Comparing the properties of the ancient AIMs (aAIMs) candidates (Figure S5a), we found that Infocalc prioritized

Summary

Introduction

Genomic techniques have been reshaping our fundamental understanding of human prehistory and origins [1]. Ancient DNA (aDNA) human genomes have assisted in investigations of population structure, human migration, human adaptation, agricultural lifestyle, and disease co-evolution [2]. Ancient genome studies have already accelerated progress in the search for genetic variations underlying the inheritance of adaptations and forensics traits. Cassidy et al [3] tested the allelic association of cystic fibrosis and hemochromatosis in ancient Irish samples, expanding genetic epidemiology onto ancient genomes. Such studies can potentially identify new risk factors for rare diseases

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