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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2011)

In this work, I develop computational tools focused around the utilization of DNA sequence data to address questions relative to forensic science, medical genetics, human evolution and ancient DNA.

First, I compute the theoretical probability that two individual profiles match by chance at two loci in a subdivided population. This question is of particular interest in forensic science, where DNA evidence has become a widespread tool of investigation and criminal conviction. I find that the effect of ignoring population subdivision can be unfavorable to

the defendant, but that the two loci can essentially be treated as unlinked.

Second, I develop a method to identify genes that are interacting, or in epistasis, to produce a particular phenotype. Determining interacting genes is indeed of particular relevance in medical genetics to help map disease genes. I validate the method with simulations and

demonstrate an improved performance over existing approaches. I also apply the method to recently available genomic data from domesticated dogs, identifying genes in epistastis for the hair length phenotype - thus representing candidate genes for functional validation.

Third, I use a summary statistic of DNA sequences, the site frequency spectrum, to estimate parameters of recent human history, and to characterize the potential event of admixture between Neanderthals and humans. I find evidence for recent gene flow between

Neanderthals and Europeans, and to a lesser extent between Neanderthals and Africans.

Finally, I develop a likelihood method to jointly estimate the age and selection coefficient of an identified mutation, along with the population size, by using time serial samples. Such datasets are widespread in the fields of ancient DNA as well as experimental and viral

evolution. I validate the method through simulations. I re-analyze a recent dataset for a locus coding for the distribution of black pigmentation in horses - and estimate that the allele far predates domestication, arising between 20,000 and 13,000 years ago.

    Cover page: Population Genetics of Ancient and Modern DNA
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2020)

    Motivation

    The presence of present-day human contaminating DNA fragments is one of the challenges defining ancient DNA (aDNA) research. This is especially relevant to the ancient human DNA field where it is difficult to distinguish endogenous molecules from human contaminants due to their genetic similarity. Recently, with the advent of high-throughput sequencing and new aDNA protocols, hundreds of ancient human genomes have become available. Contamination in those genomes has been measured with computational methods often developed specifically for these empirical studies. Consequently, some of these methods have not been implemented and tested for general use while few are aimed at low-depth nuclear data, a common feature in aDNA datasets.

    Results

    We develop a new X-chromosome-based maximum likelihood method for estimating present-day human contamination in low-depth sequencing data from male individuals. We implement our method for general use, assess its performance under conditions typical of ancient human DNA research, and compare it to previous nuclear data-based methods through extensive simulations. For low-depth data, we show that existing methods can produce unusable estimates or substantially underestimate contamination. In contrast, our method provides accurate estimates for a depth of coverage as low as 0.5× on the X-chromosome when contamination is below 25%. Moreover, our method still yields meaningful estimates in very challenging situations, i.e. when the contaminant and the target come from closely related populations or with increased error rates. With a running time below 5 min, our method is applicable to large scale aDNA genomic studies.

    Availability and implementation

    The method is implemented in C++ and R and is available in github.com/sapfo/contaminationX and popgen.dk/angsd.
      Creative Commons 'BY-NC-ND' version 4.0 license
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2020)

      Motivation

      The presence of present-day human contaminating DNA fragments is one of the challenges defining ancient DNA (aDNA) research. This is especially relevant to the ancient human DNA field where it is difficult to distinguish endogenous molecules from human contaminants due to their genetic similarity. Recently, with the advent of high-throughput sequencing and new aDNA protocols, hundreds of ancient human genomes have become available. Contamination in those genomes has been measured with computational methods often developed specifically for these empirical studies. Consequently, some of these methods have not been implemented and tested for general use while few are aimed at low-depth nuclear data, a common feature in aDNA datasets.

      Results

      We develop a new X-chromosome-based maximum likelihood method for estimating present-day human contamination in low-depth sequencing data from male individuals. We implement our method for general use, assess its performance under conditions typical of ancient human DNA research, and compare it to previous nuclear data-based methods through extensive simulations. For low-depth data, we show that existing methods can produce unusable estimates or substantially underestimate contamination. In contrast, our method provides accurate estimates for a depth of coverage as low as 0.5× on the X-chromosome when contamination is below 25%. Moreover, our method still yields meaningful estimates in very challenging situations, i.e. when the contaminant and the target come from closely related populations or with increased error rates. With a running time below 5 min, our method is applicable to large scale aDNA genomic studies.

      Availability and implementation

      The method is implemented in C++ and R and is available in github.com/sapfo/contaminationX and popgen.dk/angsd.
        Cover page: A likelihood method for estimating present-day human contamination in ancient male samples using low-depth X-chromosome data
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2014)

        Summary

        We present bammds, a practical tool that allows visualization of samples sequenced by second-generation sequencing when compared with a reference panel of individuals (usually genotypes) using a multidimensional scaling algorithm. Our tool is aimed at determining the ancestry of unknown samples-typical of ancient DNA data-particularly when only low amounts of data are available for those samples.

        Availability and implementation

        The software package is available under GNU General Public License v3 and is freely available together with test datasets https://savannah.nongnu.org/projects/bammds/. It is using R (http://www.r-project.org/), parallel (http://www.gnu.org/software/parallel/), samtools (https://github.com/samtools/samtools).

        Contact

        bammds-users@nongnu.org

        Supplementary information

        Supplementary data are available at Bioinformatics online.
          Cover page: bammds: a tool for assessing the ancestry of low-depth whole-genome data using multidimensional scaling (MDS)Creative Commons 'BY-NC-ND' version 4.0 license
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2014)

          Background

          Rapa Nui (Easter Island), located in the easternmost corner of the Polynesian Triangle, is one of the most isolated locations on the planet inhabited by humans. Archaeological and genetic evidence suggests that the island was first colonized by Polynesians around AD 1200, during their eastward expansion. Although it remains contentious whether Polynesians reached South America, suggestive evidence has been brought forward supporting the possibility of Native American contact prior to the European "discovery" of the island in AD 1722.

          Results

          We generated genome-wide data for 27 Rapanui. We found a mostly Polynesian ancestry among Rapanui and detected genome-wide patterns consistent with Native American and European admixture. By considering the distribution of local ancestry tracts of eight unrelated Rapanui, we found statistical support for Native American admixture dating to AD 1280-1495 and European admixture dating to AD 1850-1895.

          Conclusions

          These genetic results can be explained by one or more pre-European trans-Pacific contacts.
            Cover page: Genome-wide Ancestry Patterns in Rapanui Suggest Pre-European Admixture with Native AmericansCreative Commons 'BY-NC-ND' version 4.0 license
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2018)
            The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype-phenotype comparisons.
              Cover page: Human bony labyrinth is an indicator of population history and dispersal from Africa
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2014)
              The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from central Siberia, European Mesolithic hunter-gatherers, some contemporary western Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki 14 genome shows evidence of shared ancestry with a population basal to all Eurasians that also relates to later European Neolithic farmers. We find that Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than present Europeans. Our findings reveal the timing of divergence of western Eurasians and East Asians to be more than 36,200 years ago and that European genomic structure today dates back to the Upper Paleolithic and derives from a metapopulation that at times stretched from Europe to central Asia.
                Cover page: Genomic structure in Europeans dating back at least 36,200 yearsCreative Commons 'BY-NC-ND' version 4.0 license
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2014)
                Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 (14)C years before present (bp) (13,000 to 12,600 calendar years bp). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology. However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans. An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum. Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 ± 35 (14)C years bp (approximately 12,707-12,556 calendar years bp) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4× and show that the gene flow from the Siberian Upper Palaeolithic Mal'ta population into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years bp. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.
                  Cover page: The genome of a Late Pleistocene human from a Clovis burial site in western MontanaCreative Commons 'BY-NC-ND' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2014)
                  Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 (14)C years before present (bp) (13,000 to 12,600 calendar years bp). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology. However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans. An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum. Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 ± 35 (14)C years bp (approximately 12,707-12,556 calendar years bp) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4× and show that the gene flow from the Siberian Upper Palaeolithic Malta population into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years bp. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.
                    Cover page: The genome of a Late Pleistocene human from a Clovis burial site in western Montana.
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2014)
                    Understanding the peopling of the Americas remains an important and challenging question. Here, we present (14)C dates, and morphological, isotopic and genomic sequence data from two human skulls from the state of Minas Gerais, Brazil, part of one of the indigenous groups known as Botocudos. We find that their genomic ancestry is Polynesian, with no detectable Native American component. Radiocarbon analysis of the skulls shows that the individuals had died prior to the beginning of the 19th century. Our findings could either represent genomic evidence of Polynesians reaching South America during their Pacific expansion, or European-mediated transport.
                      Cover page: Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil.
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