Biology subjects

Cruz Davalos, D. I.

Publications and source records attributed to Cruz Davalos, D. I..

3 recordsLinked to original sources

bioRxiv2022

Imputation of ancient genomes

Due to postmortem DNA degradation, most ancient genomes sequenced to date have low depth of coverage, preventing the true underlying genotypes from being recovered. Genotype imputation has been put forward to improve genotyping accuracy for low-coverage genomes. However, it is unknown to what extent imputation of ancient genomes produces accurate genotypes and whether imputation introduces bias to downstream analyses. To address these questions, we downsampled 43 ancient genomes, 42 of which are high-coverage (above 10x) and three constitute a trio (mother, father and son), from different times and continents to simulate data with coverage in the range of 0.1x-2.0x and imputed these using state-of-the-art methods and reference panels. We assessed imputation accuracy across ancestries and depths of coverage. We found that ancient and modern DNA imputation accuracies were comparable. We imputed most of the 42 high-coverage genomes downsampled to 1x with low error rates (below 5%) and estimated higher error rates for African genomes, which are underrepresented in the reference panel. We used the ancient trio data to validate imputation and phasing results using an orthogonal approach based on Mendels rules of inheritance. This resulted in imputation and switch error rates of 1.9% and 2.0%, respectively, for 1x genomes. We further compared the results of downstream analyses between imputed and high-coverage genomes, notably principal component analysis (PCA), genetic clustering, and runs of homozygosity (ROH). For these three approaches, we observed similar results between imputed and high-coverage genomes using depths of coverage of at least 0.5x, except for African genomes, for which the decreased imputation accuracy impacted ROH estimates. Altogether, these results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method with potential to expand and improve ancient DNA studies.

genomics↗

bioRxiv2022

Indigenous peoples in eastern Brazil: insights from 19th century genomes and metagenomes

Although Brazil was inhabited by more than 3,000 Indigenous populations prior to European colonization, todays Indigenous peoples represent less than 1% of Brazils census population. Some of the decimated communities belonged to the so-called "Botocudos" from central-eastern Brazil. These peoples are thought to represent a case of long-standing genetic continuity bearing a strong craniometric resemblance to that of the oldest Indigenous Americans ("Paleoamericans"). Yet, little is known about their origins and genetic relationship to other Native Americans, as only two "Botocudo" genomes have been sequenced so far and those were surprisingly of Polynesian ancestry. To deepen our knowledge on the genomic history of pre-contact Indigenous Americans and the pathogens they were exposed to, we carbon-dated and sequenced 24 ancient Brazilians (including 22 "Botocudos") whose remains were hosted at the National Museum of Rio de Janeiro and recovered prior to the tragic 2018 fire. The resulting genomes depth of coverage ranged from 0.001x to 24x. Their genetic ancestry was found to be Indigenous American without gene flow from external populations such as Europeans, Africans or Polynesians. Unlike Mesoamericans, the "Botocudos" and Amazonians do not seem to have experienced a population expansion once in the Americas. Moreover, remarkably, their genomes exhibit amongst the lowest levels of heterozygosity worldwide and long runs of homozygosity, which could be explained by unique social practices or a very small effective size. Finally, whole genomes of likely ancient pathogens were recovered, including lineages of Human parvovirus B19 that were possibly introduced after the European contact. Significance statementTo better understand the genetic relationship among Indigenous populations in Brazil, we sequenced the genomes of 24 ancient individuals (22 of which labelled as "Botocudos", a term used to describe hunter-gatherer tribes) whose remains were hosted at the Museu Nacional of Rio de Janeiro prior to the tragic fire that consumed it in 2018. Unlike two previously published "Botocudo" genomes, the 22 "Botocudos" from this study have Indigenous American-related ancestry without any Polynesian-related ancestry, and they are similarly related to several Native Brazilian populations. Finally, unlike Eurasian hunter-gatherers, the "Botocudos" exhibit among the lowest heterozygosity and longest runs of homozygosity worldwide - compatible with a very small effective size and suggesting a unique social structure among hunter-gatherers in the Americas.

genomics↗

bioRxiv2017

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

BackgroundAs 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 3,000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC+Y) versus non-enriched (pre-capture) libraries.\n\nResultsWe recovered 17-4,152 times more targeted unique Y-chromosome sequences after capture, where 0.01-6.2% (WGC+Y) and 0.01-23.5% (YCC) of the sequence reads were on-target, compared to 0.0002-0.004% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC+Y) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, WGC+Y yielded greater enrichment than YCC alone. 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.\n\nConclusionsWe present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC+Y 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 for low-complexity libraries, as clonality increases considerably with each round.

genomics↗