The Simons Genome Diversity Project: A Global Analysis of Mobile Element Diversity.

Lynn B Jorde,Swapon Mallick,Jainy Thomas,Clement Goubert,W Scott Watkins,Julie E Feusier,Sarah Schaack

doi:10.1093/gbe/evaa086

Abstract

Ongoing retrotransposition of Alu, LINE-1, and SINE–VNTR–Alu elements generates diversity and variation among human populations. Previous analyses investigating the population genetics of mobile element insertions (MEIs) have been limited by population ascertainment bias or by relatively small numbers of populations and low sequencing coverage. Here, we use 296 individuals representing 142 global populations from the Simons Genome Diversity Project (SGDP) to discover and characterize MEI diversity from deeply sequenced whole-genome data. We report 5,742 MEIs not originally reported by the 1000 Genomes Project and show that high sampling diversity leads to a 4- to 7-fold increase in MEI discovery rates over the original 1000 Genomes Project data. As a result of negative selection, nonreference polymorphic MEIs are underrepresented within genes, and MEIs within genes are often found in the transcriptional orientation opposite that of the gene. Globally, 80% of Alu subfamilies predate the expansion of modern humans from Africa. Polymorphic MEIs show heterozygosity gradients that decrease from Africa to Eurasia to the Americas, and the number of MEIs found uniquely in a single individual are also distributed in this general pattern. The maximum fraction of MEI diversity partitioned among the seven major SGDP population groups (FST) is 7.4%, similar to, but slightly lower than, previous estimates and likely attributable to the diverse sampling strategy of the SGDP. Finally, we utilize these MEIs to extrapolate the primary Native American shared ancestry component to back to Asia and provide new evidence from genome-wide identical-by-descent genetic markers that add additional support for a southeastern Siberian origin for most Native Americans.

Highlights

In humans, a single class of transposable elements, the retrotransposons, accounts for most current mobile DNA activity (Beck et al 2011; Kazazian and Moran 2017)
We present thousands of new mobile element insertions (MEIs), quantify the genetic relationships among populations and individuals using MEI and comparative single nucleotide polymorphism (SNP) data, examine population sampling strategies for estimating diversity, use MEI-based ancestry estimates to analyze the origins of New World population in Asia, and quantify Alu subfamily activity in the Simons Genome Diversity Project (SGDP) populations
LINE-1, and SVA retrotransposons were identified and genotyped in 296 individuals from 75 geopolitical regions represented in the SGDP

Summary

Introduction

A single class of transposable elements, the retrotransposons, accounts for most current mobile DNA activity (Beck et al 2011; Kazazian and Moran 2017). Retrotransposition produces de novo insertions that are mostly unbiased with respect to genomic location, constrained only to a limited degree by the loose sequence specificity of the LINE-1 encoded endonuclease/reverse transcriptase that catalyzes retrotransposition (Flasch et al 2019; Sultana et al 2019) This process gives rise to insertion/deletion polymorphisms that are identical by decent, have known ancestral and derived states, and are essentially homoplasy free (Batzer and Deininger 2002; Doronina et al 2019). We leverage the genomic diversity of the Simons Genome Diversity Project (SGDP) (Mallick et al 2016) to investigate the global population dynamics of polymorphic Alu, LINE-1, and SVA elements These data are drawn from 296 deeply sequenced (43Â average depth) whole genomes from 142 populations in 75 well-defined geographic regions of the Old and New World and include many populations never before assayed for mobile element diversity. We present thousands of new MEIs, quantify the genetic relationships among populations and individuals using MEI and comparative single nucleotide polymorphism (SNP) data, examine population sampling strategies for estimating diversity, use MEI-based ancestry estimates to analyze the origins of New World population in Asia, and quantify Alu subfamily activity in the SGDP populations

Results and Discussion

Materials and Methods

Literature Cited