Improvement in detection of minor alleles in next generation sequencing by base quality recalibration

Recalibrated base quality scores for simulated data analyzed with different methods, compared to the empirical score. The ideal (diagonal) line is shown in each plot. The Frequency-Weighted Squared Error (FWSE) is given for each method. Raw: Illumina default sequencer; GATK: Mapping to the consensus sequence and the known minor alleles (MAF > 5 %) are used as the known SNPs. Seg: this study; Seg_half: the same as Seg but with half of the reads chosen randomly for the training set. (PDF 6 kb

Ancient west Eurasian ancestry in southern and eastern Africa

The history of southern Africa involved interactions between indigenous hunter-gatherers and a range of populations that moved into the region. Here we use genome-wide genetic data to show that there are at least two admixture events in the history of Khoisan populations (southern African hunter-gatherers and pastoralists who speak non-Bantu languages with click consonants). One involved populations related to Niger-Congo-speaking African populations, and the other introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We date this latter admixture event to approximately 900-1,800 years ago, and show that it had the largest demographic impact in Khoisan populations that speak Khoe-Kwadi languages. A similar signal of west Eurasian ancestry is present throughout eastern Africa. In particular, we also find evidence for two admixture events in the history of Kenyan, Tanzanian, and Ethiopian populations, the earlier of which involved populations related to west Eurasians and which we date to approximately 2,700 - 3,300 years ago. We reconstruct the allele frequencies of the putative west Eurasian population in eastern Africa, and show that this population is a good proxy for the west Eurasian ancestry in southern Africa. The most parsimonious explanation for these findings is that west Eurasian ancestry entered southern Africa indirectly through eastern Africa.Comment: Added additional simulations, some additional discussio

Multiplex DNA Typing of Short-Tandem-Repeat Loci on the Y Chromosome

This is the published version. Copyright 1997 de Gruyter.To facilitate evolutionary and forensic studies of DNA polymorphisms on the Y chromosome, we devised a multiplex amplification procedure for short-tandemrepeat (STR) loci. Four tetranucleotide STR loci (DYS19, DYS390, DYS391, and DYS393) were simultaneously amplified with FAM-labeled primers and genotypes were determined with an automated DNA sequencer. We typed 162 males from three U.S. populations (African-Americans, European-Americans and Hispanics) and found that the haplotype diversities range from 0.920 to 0.969. This quadruplex system provides a facile means of genotyping these Y chromosome STRs, and should be useful in population genetic and forensic applications

In search of polymorphic Alu insertions with restricted geographic distributions

Alu elements are transposable elements that have reached over one million copies in the human genome. Some Alu elements inserted in the genome so recently that they are still polymorphic for insertion presence or absence in human populations. Recently, there has been an increasing interest in using Alu variation for studies of human population genetic structure and inference of individual geographic origin. Currently, this requires a high number of Alu loci. Here, we used a linker-mediated polymerase chain reaction method to preferentially identify low-frequency Alu elements in various human DNA samples with different geographic origins. The candidate Alu loci were subsequently genotyped in 18 worldwide human populations (∼370 individuals), resulting in the identification of two new Alu insertions restricted to populations of African ancestry. Our results suggest that it may ultimately become possible to correctly infer the geographic affiliation of unknown samples with high levels of confidence without having to genotype as many as 100 Alu loci. This is desirable if Alu insertion polymorphisms are to be used for human evolution studies or forensic applications. © 2007 Elsevier Inc. All rights reserved

Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis

<p>Abstract</p> <p>Background</p> <p>Uncoupling protein 1 (UCP1) is a mitochondrial anion carrier, expressed in brown adipose tissue (BAT) of Eutherians. UCP1 is responsible for uncoupling mitochondrial proton transport from the production of ATP, thereby dissipating heat; it is essential for non-shivering thermogenesis (NST) in mammalian BAT. UCP1 orthologs have been identified in non-Eutherian mammals, fish and amphibians. Yet, UCP1 has a unique function in Eutherians in that it is necessary in the production of heat (NST). As such, this study aims to determine the evolutionary mode of UCP1 in Eutherians, where there is clear evidence of UCP1-dependent NST in BAT.</p> <p>Results</p> <p>Models of adaptive evolution through phylogenetic analysis of amino acid sequences by maximum likelihood were implemented to determine the mode of UCP1 protein evolution in Eutherians. An increase in the rate of amino acid substitutions on the branch leading to Eutherians is observed, but is best explained by relaxed constraints, not positive selection. Further, evidence for branch and site heterogeneity in selection pressures, as well as divergent selection pressures between UCP1 and its paralogs (UCP2-3) is observed.</p> <p>Conclusion</p> <p>We propose that the unique thermogenic function of UCP1 in Eutherians may be best explained by neutral processes. Along with other evidence, this suggests that the primary biochemical properties of UCP1 may not differ between Eutherians and non-Eutherians.</p

Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis

<p>Abstract</p> <p>Background</p> <p>Uncoupling protein 1 (UCP1) is a mitochondrial anion carrier, expressed in brown adipose tissue (BAT) of Eutherians. UCP1 is responsible for uncoupling mitochondrial proton transport from the production of ATP, thereby dissipating heat; it is essential for non-shivering thermogenesis (NST) in mammalian BAT. UCP1 orthologs have been identified in non-Eutherian mammals, fish and amphibians. Yet, UCP1 has a unique function in Eutherians in that it is necessary in the production of heat (NST). As such, this study aims to determine the evolutionary mode of UCP1 in Eutherians, where there is clear evidence of UCP1-dependent NST in BAT.</p> <p>Results</p> <p>Models of adaptive evolution through phylogenetic analysis of amino acid sequences by maximum likelihood were implemented to determine the mode of UCP1 protein evolution in Eutherians. An increase in the rate of amino acid substitutions on the branch leading to Eutherians is observed, but is best explained by relaxed constraints, not positive selection. Further, evidence for branch and site heterogeneity in selection pressures, as well as divergent selection pressures between UCP1 and its paralogs (UCP2-3) is observed.</p> <p>Conclusion</p> <p>We propose that the unique thermogenic function of UCP1 in Eutherians may be best explained by neutral processes. Along with other evidence, this suggests that the primary biochemical properties of UCP1 may not differ between Eutherians and non-Eutherians.</p

Dating the age of admixture via wavelet transform analysis of genome-wide data

We describe a PCA-based genome scan approach to analyze genome-wide admixture structure, and introduce wavelet transform analysis as a method for estimating the time of admixture. We test the wavelet transform method with simulations and apply it to genome-wide SNP data from eight admixed human populations. The wavelet transform method offers better resolution than existing methods for dating admixture, and can be applied to either SNP or sequence data from humans or other species

Genome-wide variation in the Angolan Namib Desert reveals unique pre-Bantu ancestry.

Ancient DNA studies reveal the genetic structure of Africa before the expansion of Bantu-speaking agriculturalists; however, the impact of now extinct hunter-gatherer and herder societies on the genetic makeup of present-day African groups remains elusive. Here, we uncover the genetic legacy of pre-Bantu populations from the Angolan Namib Desert, where we located small-scale groups associated with enigmatic forager traditions, as well as the last speakers of the Khoe-Kwadi family's Kwadi branch. By applying an ancestry decomposition approach to genome-wide data from these and other African populations, we reconstructed the fine-scale histories of contact emerging from the migration of Khoe-Kwadi-speaking pastoralists and identified a deeply divergent ancestry, which is exclusively shared between groups from the Angolan Namib and adjacent areas of Namibia. The unique genetic heritage of the Namib peoples shows how modern DNA research targeting understudied regions of high ethnolinguistic diversity can complement ancient DNA studies in probing the deep genetic structure of the African continent