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The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects.

European history has been shaped by migrations of people, and their subsequent admixture. Recently, evidence from ancient DNA has brought new insights into migration events that could be linked to the advent of agriculture, and possibly to the spread of Indo-European languages. However, little is known so far about the ancient population history of north-eastern Europe, in particular about populations speaking Uralic languages, such as Finns and Saami. Here we analyse ancient genomic data from 11 individuals from Finland and Northwest Russia. We show that the specific genetic makeup of northern Europe traces back to migrations from Siberia that began at least 3,500 years ago. This ancestry was subsequently admixed into many modern populations in the region, in particular populations speaking Uralic languages today. In addition, we show that ancestors of modern Saami inhabited a larger territory during the Iron Age than today, which adds to historical and linguistic evidence for the population history of Finland.

Wepresent the high-quality genome sequence of a 45,000-year-old modern human male from Siberia. This individual derives from a population that lived before¿or simultaneously with¿the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000¿13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 x 10-9 to 0.6x10-9 per site per year, a Y chromosomal mutation rate of 0.7x10-9 to 0.9x10-9 per site per year based on the additional substitutions that have occurred in present-day non- Africans compared to this genome, and a mitochondrial mutation rate of 1.8x10-8 to 3.2x10-8 per site per year based on the age of the bone.

The high-coverage genomes of a Neandertal and Denisovan individuals from the Altai Mountains in Southern Siberia have provided insights into the history and relationships of archaic and modern humans (Meyer et al., Science 2012 ; Prüfer et al., Nature 2014). The demographic history of Neandertal populations across Eurasia, however, remains largely unknown. Here we present the first integrated demographic analysis making use of the DNA sequences of chromosome 21 from two Neandertals from Spain and Croatia together with the two archaic genomes from Southern Siberia and 14 present-day humans. The analysis was conducted using the Generalized Phylogenetic Coalescent Sampler (G-PhoCS ; Gronau et al., Nat Genet 2011), a Bayesian method for robust demographic inference based on the joint analysis of small numbers of individuals from multiple populations.

The high-coverage sequencing of a Neandertal and a Denisovan individual from the Altai Mountains in Siberia provided insights into the history and relationships of these archaic individuals to modern humans (Meyer et al. 2012 ; Prüfer et al. 2014). We used densely tiled oligonucleotide probes to capture 30 million bases of the human chromosome 21 from two Neandertal individuals from El Sidrón in Spain and Vindija in Croatia, and sequenced them to 12- and 34-fold, respectively. We compared the genotypes of these individuals to the same regions from the chromosomes 21 of a Neandertal and a Denisovan, as well as to 25 presentday humans from different populations around the world. Heterozygosities in the two Neandertals from Europe are similar to that of the Denisovan individual and about one third of the lowest heterozygosity seen in the present-day humans. Only the Altai Neandertal shows a lower heterozygosity. As described, the Altai Neandertal shows a large number of large regions of homozygosity that are the result of recent inbreeding. The two European Neandertals show fewer and smaller such regions of homozygosity that are still larger than what is seen in any of the present-day humans. These results suggest that the long-term population size of Neandertals across their geographic range was low, while only the Altai Neandertal shows an excess of long homozygous regions due to recent inbreeding.

Comparisons of the genomes of Neandertals and Denisovans with present-day human genomes have suggested that the gene RUNX2, which encodes a transcription factor, may have been positively selected during early human evolution. Here, we overexpress RUNX2 in ten human cell lines and identify genes that are directly or indirectly affected by RUNX2 expression. We find a number of genes not previously known to be affected by RUNX2 expression, in particular BIRC3, genes encoded on the mitochondrial genome, and several genes involved in bone and tooth formation. These genes are likely to provide inroads into pathways affected by RUNX2 and potentially by the evolutionary changes that affected RUNX2 in modern humans.

To gain insight into the patterns of genetic variation and evolutionary relationships within and between bonobos and chimpanzees, we sequenced 150,000 base pairs of nuclear DNA divided among 15 autosomal regions as well as the complete mitochondrial genomes from 20 bonobos and 58 chimpanzees. Except for western chimpanzees, we found poor genetic separation of chimpanzees based on sample locality. In contrast, bonobos consistently cluster together but fall as a group within the variation of chimpanzees for many of the regions. Thus, while chimpanzees retain genomic variation that predates bonobo-chimpanzee speciation, extensive lineage sorting has occurred within bonobos such that much of their genome traces its ancestry back to a single common ancestor that postdates their origin as a group separate from chimpanzees.

BACKGROUND: To utilize the power of high-throughput sequencers, target enrichment methods have been developed. The majority of these require reagents and equipment that are only available from commercial vendors and are not suitable for the targets that are a few kilobases in length. METHODOLOGY/PRINCIPAL FINDINGS: We describe a novel and economical method in which custom made long-range PCR products are used to capture complete human mitochondrial genomes from complex DNA mixtures. We use the method to capture 46 complete mitochondrial genomes in parallel and we sequence them on a single lane of an Illumina GA(II) instrument. CONCLUSIONS/SIGNIFICANCE: This method is economical and simple and particularly suitable for targets that can be amplified by PCR and do not contain highly repetitive sequences such as mtDNA. It has applications in population genetics and forensics, as well as studies of ancient DNA.

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Background Genome-wide expression, sequence and association studies typically yield large sets of gene candidates, which must then be further analysed and interpreted. Information about these genes is increasingly being captured and organized in ontologies, such as the Gene Ontology. Relationships between the gene sets identified by experimental methods and biological knowledge can be made explicit and used in the interpretation of results. However, it is often difficult to assess the statistical significance of such analyses since many inter-dependent categories are tested simultaneously. Results We developed the program package FUNC that includes and expands on currently available methods to identify significant associations between gene sets and ontological annotations. Implemented are several tests in particular well suited for genome wide sequence comparisons, estimates of the family-wise error rate, the false discovery rate, a sensitive estimator of the global significance of the results and an algorithm to reduce the complexity of the results. Conclusion FUNC is a versatile and useful tool for the analysis of genome-wide data. It is freely available under the GPL license and also accessible via a web service.

Background: It has long been argued that changes in gene expression may provide an additional\ud and crucial perspective on the evolutionary differences between humans and chimpanzees. To\ud investigate how often expression differences seen in tissues are caused by sequence differences in\ud the proximal promoters, we tested the expression activity in cultured cells of human and\ud chimpanzee promoters from genes that differ in mRNA expression between human and\ud chimpanzee tissues.\ud Results: Twelve promoters for which the corresponding gene had been shown to be differentially\ud expressed between humans and chimpanzees in liver or brain were tested. Seven showed a\ud significant difference in activity between the human promoter and the orthologous chimpanzee\ud promoter in at least one of the two cell lines used. However, only three of them showed a\ud difference in the same direction as in the tissues.\ud Conclusion: Differences in proximal promoter activity are likely to be common between humans\ud and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This\ud suggests that several genetic differences between humans and chimpanzees might be responsible\ud for a single expression difference and thus that relevant expression differences between humans\ud and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.

BACKGROUND: Numerous studies have employed microarray techniques to study changes in gene expression in connection with human disease, aging and evolution. The vast majority of human samples available for research are obtained from deceased individuals. This raises questions about how well gene expression patterns in such samples reflect those of living individuals. RESULTS: Here, we compare gene expression patterns in two human brain regions in postmortem samples and in material collected during surgical intervention. We find that death induces significant expression changes in more than 10% of all expressed genes. These changes are non-randomly distributed with respect to their function. Moreover, we observe similar expression changes due to death in two distinct brain regions. Consequently, the pattern of gene expression differences between the two brain regions is largely unaffected by death, although the magnitude of differences is reduced by 50% in postmortem samples. Furthermore, death-induced changes do not contribute significantly to gene expression variation among postmortem human brain samples. CONCLUSION: We conclude that postmortem human brain samples are suitable for investigating gene expression patterns in humans, but that caution is warranted in interpreting results for individual genes.

Résumé dans Bulletins et Mémoires de la Société d'Anthropologie de Paris, 16 (3-4), p. 237

mtDNA sequences were determined from 241 individuals from nine ethnic groups in Africa. When they were compared with published data from other groups, it was found that the !Kung, Mbuti, and Biaka show on the order of 10 times more sequence differences between the three groups, as well as between those and the other groups (the Fulbe, Hausa, Tuareg, Songhai, Kanuri, Yoruba, Mandenka, Somali, Tukana, and Kikuyu), than these other groups do between one other. Furthermore, the pairwise sequence distributions, patterns of coalescence events, and numbers of variable positions relative to the mean sequence difference indicate that the former three groups have been of constant size over time, whereas the latter have expanded in size. We suggest that this reflects subsistence patterns in that the populations that have expanded in size are food producers whereas those that have not are hunters and gatherers.

DNA was extracted from approximately 600-year-old human remains found at an archaeological site in the southwestern United States, and mtDNA fragments were amplified by PCR. When these fragments were sequenced directly, multiple sequences seemed to be present. From three representative individuals, DNA fragments of different lengths were quantified and short overlapping amplification products cloned. When amplifications started from