Genome-wide nucleotide-level mammalian ancestor reconstruction

Paten, Benedict; Herrero, Javier; Fitzgerald, Stephen; Beal, Kathryn; Flicek, Paul; Holmes, Ian; Birney, Ewan

doi:10.1101/gr.076521.108

Cited by 178 publications

(180 citation statements)

References 55 publications

(83 reference statements)

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“…We excluded sex chromosomes to avoid biases due to their specific features-both in terms of mutation pattern and demography. Mutations were polarized using ancestral state predictions based on four-way multiple alignments (Homo sapiens, Pan troglodytes, Pongo pygmaeus, Macaca mulatta) (Paten et al 2008), which are provided in the original SNP data file (The 1000 Genomes Project Consortium 2012). We excluded SNPs for which information about the ancestral state was reported as being unreliable (see Methods).…”

Section: Resultsmentioning

confidence: 99%

Quantification of GC-biased gene conversion in the human genome

et al. 2015

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Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian genomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%-2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in nonAfrican than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC.

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Section: Resultsmentioning

confidence: 99%

Quantification of GC-biased gene conversion in the human genome

et al. 2015

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“…The genetic map used was that released by the HapMap Consortium (www.hapmap.org), which is averaged across the three original HapMap populations and thus is unlikely to be influenced by selection in any individual population. We determined the ancestral state of each SNP using the Ensembl EPO pipeline, which uses sequence information from five primate species to define the most likely ancestral state (63,64). To identify genomic regions with extreme jiHSj values, we used a sliding-window approach.…”

Section: Methodsmentioning

confidence: 99%

Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers

Perry

Foll

Grenier

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

108

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The evolutionary history of the human pygmy phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (east central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses, we computed the haplotypebased integrated haplotype score (iHS) statistic and the level of population differentiation (F ST ) between the Batwa and their agricultural neighbors, the Bakiga, for each genomic SNP. Both jiHSj and F ST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (west central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated jiHSj or F ST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior.human evolutionary ecology | human hunter-gatherers | population genomics | convergent evolution

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“…2, and Table S18). Derived states for alleles were determined from the inferred ancestral base in the Enredo Pecan Ortheus (EPO) six-primate genome alignments (36) and were classified as synonymous or nonsynonymous based on the gene annotation used in the array design (SI Appendix). When counting alleles in heterozygous and homozygous positions for each archaic or present-day individual (Tables S15 and S16), we used derived alleles that are ancestral in the three Africans or ancestral in the three Neandertals, respectively.…”

Section: Contamination Estimatesmentioning

confidence: 99%

Patterns of coding variation in the complete exomes of three Neandertals

Castellano

Parra

Sánchez-Quinto

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

233

230

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We present the DNA sequence of 17,367 protein-coding genes in two Neandertals from Spain and Croatia and analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia. Comparisons with present-day humans from Africa, Europe, and Asia reveal that genetic diversity among Neandertals was remarkably low, and that they carried a higher proportion of amino acid-changing (nonsynonymous) alleles inferred to alter protein structure or function than present-day humans. Thus, Neandertals across Eurasia had a smaller long-term effective population than present-day humans. We also identify amino acid substitutions in Neandertals and present-day humans that may underlie phenotypic differences between the two groups. We find that genes involved in skeletal morphology have changed more in the lineage leading to Neandertals than in the ancestral lineage common to archaic and modern humans, whereas genes involved in behavior and pigmentation have changed more on the modern human lineage.ancient DNA | exome capture | site frequency spectra | paleogenetics A nalyses of the coding regions of multiple present-day human individuals have uncovered many amino acid-changing SNPs segregating at low frequency in present-day human populations (1-7). It also has been shown that Europeans carry a larger proportion than Africans of amino acid-changing SNPs inferred to alter the structure or function of proteins and thus to be potentially deleterious (4), a fact attributed to the bottleneck and subsequent expansion of human populations during and after the migration out of Africa (4). In contrast, little is known about the coding variation in Neandertals, an extinct hominin group closely related to presentday humans. The main reasons for this are the rarity of Neandertal remains and the fact that >99% of the DNA extracted from typical Neandertal bones is derived from microbes (8, 9), making shotgun sequencing of the endogenous DNA impractical.Here, we use a hybridization approach to enrich and sequence the protein-coding fractions of the genomes of two Neandertals from Spain and Croatia. We analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia (10) and show that the genetic diversity, pattern of coding variation, and genes that may underlie phenotypic changes in Neandertals are remarkably different from those in present-day humans. Results and DiscussionWe used densely tiled oligonucleotide probes (9) and a recently described protocol (11) to capture the protein-coding exons from 17,367 genes in a ∼49,000-y-old (12) (uncalibrated radiocarbon date) Neandertal from Spain (SD1253, El Sidrón Cave) and a ∼44,000-y-old (uncalibrated radiocarbon date) Neandertal from Croatia (Vi33.15, Vindija Cave). The DNA libraries from these two Neandertals contain 0.2% and 0.5% endogenous DNA, respectively, and the capture approach enriched the endogenous DNA 325-fold and 153-fold, resulting in an average coverage of 12.5-fold and 42.0-fold for the El Sidrón and Vindi...

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Genome-wide nucleotide-level mammalian ancestor reconstruction

Cited by 178 publications

References 55 publications

Quantification of GC-biased gene conversion in the human genome

Quantification of GC-biased gene conversion in the human genome

Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers

Patterns of coding variation in the complete exomes of three Neandertals

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