A common copy-number variant within SIRPB1 correlates with human Out-of-Africa migration after genetic drift correction.

Jose Luis Royo,Arantxa Lupiañez,Joan Valls,Carlos Gómez-Marin,Mariona Pascual-Pons,Rafael D Acemel,Joan Fibla,Jose Luis Gomez-Skarmeta,Francesc Calafell

doi:10.1371/journal.pone.0193614

Abstract

Previous reports have proposed that personality may have played a role on human Out-Of-Africa migration, pinpointing some genetic variants that were positively selected in the migrating populations. In this work, we discuss the role of a common copy-number variant within the SIRPB1 gene, recently associated with impulsive behavior, in the human Out-Of-Africa migration. With the analysis of the variant distribution across forty-two different populations, we found that the SIRPB1 haplotype containing duplicated allele significantly correlated with human migratory distance, being one of the few examples of positively selected loci found across the human world colonization. Circular Chromosome Conformation Capture (4C-seq) experiments from the SIRPB1 promoter revealed important 3D modifications in the locus depending on the presence or absence of the duplication variant. In addition, a 3’ enhancer showed neural activity in transgenic models, suggesting that the presence of the CNV may compromise the expression of SIRPB1 in the central nervous system, paving the way to construct a molecular explanation of the SIRPB1 variants role in human migration.

Highlights

In South East Africa, about 100,000 years ago (y.a.) the early Homo sapiens began its expansion [1,2]
Phylogenetic analysis using MEGA revealed that the insertion allele (Dup) of the CNV comes from a recent duplication of signal regulatory protein beta-1 (SIRPB1) (Fig 1A and 1B) that can be directly visualized using UCSC genome browser in HGDP00521, one of the currently available fully sequenced donnors (Fig 1C)
We explored the region analyzing 1,532 SNPs and structural variants with a minimal allele frequency (MAF) >10% from 2,536 donnors of the 1,000 genome project

Summary

Introduction

In South East Africa, about 100,000 years ago (y.a.) the early Homo sapiens began its expansion [1,2]. According to mitochondrial DNA data, they followed the northeast coastline of Africa and continued their migration to the Middle East and next to Southern Asia and reached Australia. About 40,000 y.a., humans moved from Middle East north-west into Europe. Almost at the same time, modern humans crossed the Bering strait between Asia and North America and started a north-to-south expansion. The initial spread of humanity across the Earth was driven primarily by food and climate [3]. Some authors have proposed that these movements may had not been merely due to environmental circumstances and probably some innate personality variables played a role on the final decisions. From a neurological point of view, there are evidences supporting that the prefrontal cortex is both

Methods

Results

Conclusion