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Background: As most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach—in-solution capture-enrichment—retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre-capture) libraries. Results: The six samples show different levels of initial endogenous content, with very low (< 0.05%, 4 samples) or low (0.1–1.54%, 2 samples) percentages of sequenced reads mapping to the human genome. We recover 12–9549 times more targeted unique Y-chromosome sequences after capture, where 0.0–6.2% (WGC + YCC) and 0.0–23.5% (YCC) of the sequence reads were on-target, compared to 0.0–0.00003% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC + YCC) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, the libraries’ initial low complexity leads to minor proportions of Y-chromosome reads. Finally, increasing recovery of informative sites enabled us to assign Y-chromosome haplogroups to some of the archeological remains and gain insights about their paternal lineages and origins. Conclusions: We present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC + YCC enrichments lead to an increase in the amount of Y-DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our probe design effectively recovers regions of the Y-chromosome bearing phylogenetically informative sites, allowing us to identify paternal lineages with less sequencing than needed for pre-capture libraries. Finally, we recommend considering the endogenous content in the experimental design and avoiding consecutive rounds of capture, as clonality increases considerably with each round. [ABSTRACT FROM AUTHOR]

The extent to which prehistoric migrations of farmers influenced the genetic pool of western North Africans remains unclear. Archaeological evidence suggests that the Neolithization process may have happened through the adoption of innovations by local Epipaleolithic communities or by demic diffusion from the Eastern Mediterranean shores or Iberia. Here, we present an analysis of individuals' genome sequences from Early and Late Neolithic sites in Morocco and from Early Neolithic individuals from southern Iberia. We show that Early Neolithic Moroccans (~5,000 BCE) are similar to Later Stone Age individuals from the same region and possess an endemic element retained in present-day Maghrebi populations, confirming a long-term genetic continuity in the region. This scenario is consistent with Early Neolithic traditions in North Africa deriving from Epipaleolithic communities that adopted certain agricultural techniques from neighboring populations. Among Eurasian ancient populations, Early Neolithic Moroccans are distantly related to Levantine Natufian hunter-gatherers (~9,000 BCE) and Pre-Pottery Neolithic farmers (~6,500 BCE). Late Neolithic (~3,000 BCE) Moroccans, in contrast, share an Iberian component, supporting theories of trans-Gibraltar gene flow and indicating that Neolithization of North Africa involved both the movement of ideas and people. Lastly, the southern Iberian Early Neolithic samples share the same genetic composition as the Cardial Mediterranean Neolithic culture that reached Iberia ~5,500 BCE. The cultural and genetic similarities between Iberian and North African Neolithic traditions further reinforce the model of an Iberian migration into the Maghreb. [ABSTRACT FROM AUTHOR]

We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30–40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene. [ABSTRACT FROM AUTHOR]

Reduced representation sequencing methods such as genotyping-by-sequencing (GBS) enable low-cost measurement of genetic variation without the need for a reference genome assembly. These methods are widely used in genetic mapping and population genetics studies, especially with non-model organisms. Variant calling error rates, however, are higher in GBS than in standard sequencing, in particular due to restriction site polymorphisms, and few computational tools exist that specifically model and correct these errors. We developed a statistical method to remove errors caused by restriction site polymorphisms, implemented in the software package GBStools. We evaluated it in several simulated data sets, varying in number of samples, mean coverage and population mutation rate, and in two empirical human data sets (N = 8 and N = 63 samples). In our simulations, GBStools improved genotype accuracy more than commonly used filters such as Hardy-Weinberg equilibrium p-values. GBStools is most effective at removing genotype errors in data sets over 100 samples when coverage is 40X or higher, and the improvement is most pronounced in species with high genomic diversity. We also demonstrate the utility of GBS and GBStools for human population genetic inference in Argentine populations and reveal widely varying individual ancestry proportions and an excess of singletons, consistent with recent population growth. [ABSTRACT FROM AUTHOR]