In-solution Y-chromosome capture-enrichment on ancient DNA libraries

Diana I. Cruz-Dávalos, María A. Nieves-Colón, Alexandra Sockell, G. David Poznik, Hannes Schroeder, Anne C. Stone, Carlos D. Bustamante, Anna Sapfo Malaspinas, María C. Ávila-Arcos

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number608
JournalBMC Genomics
Issue number1
StatePublished - Aug 14 2018
Externally publishedYes

Bibliographical note

Funding Information:
MCAA’s laboratory is supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica - Universidad Nacional Autónoma de México grant IA206817. DICD and ASM are funded by the Swiss National Science foundation and the European Research Council (ERC starting grant). HS was funded by the European Research Council (FP7/2007–2013, grant no. 319209, Synergy project NEXUS1492). The work on the samples from Saint Martin was partially funded by the European Commission through the Marie Curie Actions (FP7/2007–2013, grant no. 290344, EUROTAST). Funding for work with the Puerto Rico samples was provided by the Arizona State University School of International Letters and Cultures Foster Latin American Studies Support Grant, the Arizona State University Graduate and Professional Student Association and Sigma-Xi.

Publisher Copyright:
© 2018 The Author(s).


  • Ancient DNA
  • Capture-enrichment
  • Y chromosome


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