Genome-wide scan of 29,141 African Americans finds no evidence of selection since admixture
Gaurav Bhatia, Arti Tandon, Melinda C. Aldrich, Christine B. Ambrosone, Christopher Amos, Elisa V. Bandera, Sonja I. Berndt, Leslie Bernstein, William J. Blot, Cathryn H. Bock, Neil Caporaso, Graham Casey, Sandra L. Deming, W. Ryan Diver, Susan M. Gapstur, Elizabeth M. Gillanders, Curtis C. Harris, Brian E. Henderson, Sue A. Ingles, William Isaacs, Esther M. John, Rick A. Kittles, Emma Larkin, Lorna H. McNeill, Robert C. Millikan, Adam Murphy, Christine Neslund-Dudas, Sarah Nyante, Michael F. Press, Jorge L. Rodriguez-Gil, Benjamin A. Rybicki, Ann G. Schwartz, Lisa B. Signorello, Margaret Spitz, Sara S. Strom, Margaret A. Tucker, John K. Wiencke, John S. Witte, Xifeng Wu, Yuko Yamamura, Krista A. Zanetti, Wei Zheng, Regina G. Ziegler, Stephen J. Chanock, Christopher A. Haiman, David Reich, Alkes L. Price
(Submitted on 10 Dec 2013)

We scanned through the genomes of 29,141 African Americans, searching for loci where the average proportion of African ancestry deviates significantly from the genome-wide average. We failed to find any genome-wide significant deviations, and conclude that any selection in African Americans since admixture is sufficiently weak that it falls below the threshold of our power to detect it using a large sample size. These results stand in contrast to the findings of a recent study of selection in African Americans. That study, which had 15 times fewer samples, reported six loci with significant deviations. We show that the discrepancy is likely due to insufficient correction for multiple hypothesis testing in the previous study. The same study reported 14 loci that showed greater population differentiation between African Americans and Nigerian Yoruba than would be expected in the absence of natural selection. Four such loci were previously shown to be genome-wide significant and likely to be affected by selection, but we show that most of the 10 additional loci are likely to be false positives. Additionally, the most parsimonious explanation for the loci that have significant evidence of unusual differentiation in frequency between Nigerians and Africans Americans is selection in Africa prior to their forced migration to the Americas.

Human blood genotypes dynamics
Timur Sadykov
(Submitted on 9 Dec 2013)

We give a complete closed form description of the evolution of human blood genotypes frequencies (in the ABO and Rh classification) after any (finite or infinite) number of generations and for any initial distribution.

Error-prone polymerase activity causes multinucleotide mutations in humans
Kelley Harris, Rasmus Nielsen
(Submitted on 5 Dec 2013)

About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1,092 human genomes, demonstrating that MNMs become enriched as large numbers of individuals are sampled. We leverage the size of the dataset to deduce new information about the allelic spectrum of MNMs, estimating the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between the affected sites and showing that MNMs exhibit a high percentage of transversions relative to transitions. These findings are reproducible in data from multiple sequencing platforms. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived dinucleotides, with GC→AA, GA→TT and their reverse complements making up 36% of the total. These same mutations dominate the spectrum of tandem mutations produced by the upregulation of low-fidelity Polymerase ζ in mutator strains of S. cerevisiae that have impaired DNA excision repair machinery. This suggests that low-fidelity DNA replication by Pol ζ is at least partly responsible for the MNMs that are segregating in the human population, and that useful information about the biochemistry of MNM can be extracted from ordinary population genomic data. We incorporate our findings into a mathematical model of the multinucleotide mutation process that can be used to correct phylogenetic and population genetic methods for the presence of MNMs.

Interspecific Introgressive Origin of Genomic Diversity in the House Mouse
Kevin J. Liu, Ying Song, Michael H. Kohn, Luay Nakhleh
(Submitted on 22 Nov 2013)

We report on a genome-wide scan for introgression in a eukaryote. The scan identified kilobase-to-megabase-long regions of introgressive origin involving Mus spretus in six Mus musculus domesticus chromosomes, based on genomes sampled from and near the European range of sympatry. Our analyses point to the introgression of both adaptive driver and linked passenger loci. Introgression could transfer traits, such as the discovered warfarin resistance in European M. m. domesticus, and could create new traits, as we infer using a functional network analysis. Our study sheds new light on the extent of adaptive introgession and calls for new analyses of eukaryotic genomes that explicitly account for the possibility of introgression.

A Complete Public Domain Family Genomics Dataset
Manuel Corpas, Mike Cariaso, Alain Coletta, David Weiss, Andrew P Harrison, Federico Moran, Huanming Yang

BACKGROUND: The availability of open access genomic data is essential for the personal genomics field. Public genomic data allow comparative analyses, testing of new tools and genotype-phenotype association studies. Personal genomics data of unrelated individuals are available in the public domain, notably the Personal Genome Project; however, to date genomics family data and metadata are severely lacking, mainly due to cost, privacy concerns or restricted access to Next Generation Sequencing (NGS) technology. Family data have a lot to offer as they allow the study of heritability, something which is impossible to do just by using unrelated individuals. FINDINGS: A whole family from Southern Spain decided to genotype, sequence and analyse their personal genomes making them publicly available under a Creative Commons 0 license (CC0; commonly denominated as public domain). These data include a) five 23andMe SNP chip genotype bed files, b) four raw exomes with their assorted bam files and VCF files, c) a metagenomic raw sequencing data file and d) derived data of likely phenotypes using SNPedia-derived tools. CONCLUSIONS: To our knowledge this is the first CC0 released set of genomic, phenotypic and metagenomic data for a whole family. This dataset is also unique in that it was obtained through direct-to-consumer genetic tests. Hence any ordinary citizen with enough budget and samples should be able to reproduce this experiment. We envisage this dataset to be a useful resource for a variety of applications in the personal genomics field as a) negative control data for trait association discovery, b) testing data for development of new software and c) sample data for heritability studies. We encourage prospective users to share with us derived results so that they can be added to our existing collection.

Population genomics of parallel hybrid zones in the mimetic butterflies, H. melpomene and H. erato

Nicola Nadeau, Mayte Ruiz, Patricio Salazar, Brian Counterman, Jose Alejandro Medina, Humberto Ortiz-Zuazaga, Anna Morrison, W. Owen McMillan, Chri Jiggins, Riccardo Papa

Hybrid zones can be valuable tools for studying evolution and identifying genomic regions responsible for adaptive divergence and underlying phenotypic variation. Hybrid zones between subspecies of Heliconius butterflies can be very narrow and are maintained by strong selection acting on colour pattern. The co-mimetic species H. erato and H. melpomene have parallel hybrid zones where both species undergo a change from one colour pattern form to another. We use restriction associated DNA sequencing to obtain several thousand genome wide sequence markers and use these to analyse patterns of population divergence across two pairs of parallel hybrid zones in Peru and Ecuador. We compare two approaches for analysis of this type of data; alignment to a reference genome and de novo assembly, and find that alignment gives the best results for species both closely (H. melpomene) and distantly (H. erato, ~15% divergent) related to the reference sequence. Our results confirm that the colour pattern controlling loci account for the majority of divergent regions across the genome, but we also detect other divergent regions apparently unlinked to colour pattern differences. We also use association mapping to identify previously unmapped colour pattern loci, in particular the Ro locus. Finally, we identify within our sample a new cryptic population of H. timareta in Ecuador, which occurs at relatively low altitude and is mimetic with H. melpomene malleti.

The genomic landscape of meiotic crossovers and gene conversions in Arabidopsis thaliana
Erik Wijnker, Geo Velikkakam James, Jia Ding, Frank Becker, Jonas R. Klasen, Vimal Rawat, Beth A. Rowan, Daniel F. de Jong, C. Bastiaan de Snoo, Luis Zapata, Bruno Huettel, Hans de Jong, Stephan Ossowski, Detlef Weigel, Maarten Koornneef, Joost J.B. Keurentjes, Korbinian Schneeberger
(Submitted on 13 Nov 2013)

Knowledge of the exact distribution of meiotic crossovers (COs) and gene conversions (GCs) is essential for understanding many aspects of population genetics and evolution, from haplotype structure and long-distance genetic linkage to the generation of new allelic variants of genes. To this end, we resequenced the four products of 13 meiotic tetrads along with 10 doubled haploids derived from Arabidopsis thaliana hybrids. GC detection through short reads has previously been confounded by genomic rearrangements. Rigid filtering for misaligned reads allowed GC identification at high accuracy and revealed an ~80-kb transposition, which undergoes copy-number changes mediated by meiotic recombination. Non-crossover associated GCs were extremely rare most likely due to their short average length of ~25-50 bp, which is significantly shorter than the length of CO associated GCs. Overall, recombination preferentially targeted non-methylated nucleosome-free regions at gene promoters, which showed significant enrichment of two sequence motifs.