Autosomal resequence data reveal Late Stone Age signals of population expansion in sub-Saharan African foraging and farming populations.

BACKGROUND: A major unanswered question in the evolution of Homo sapiens is when anatomically modern human populations began to expand: was demographic growth associated with the invention of particular technologies or behavioral innovations by hunter-gatherers in the Late Pleistocene, or with the acquisition of farming in the Neolithic? METHODOLOGY/PRINCIPAL FINDINGS: We investigate the timing of human population expansion by performing a multilocus analysis of > or = 20 unlinked autosomal noncoding regions, each consisting of approximately 6 kilobases, resequenced in approximately 184 individuals from 7 human populations. We test the hypothesis that the autosomal polymorphism data fit a simple two-phase growth model, and when the hypothesis is not rejected, we fit parameters of this model to our data using approximate Bayesian computation. CONCLUSIONS/SIGNIFICANCE: The data from the three surveyed non-African populations (French Basque, Chinese Han, and Melanesians) are inconsistent with the simple growth model, presumably because they reflect more complex demographic histories. In contrast, data from all four sub-Saharan African populations fit the two-phase growth model, and a range of onset times and growth rates is inferred for each population. Interestingly, both hunter-gatherers (San and Biaka) and food-producers (Mandenka and Yorubans) best fit models with population growth beginning in the Late Pleistocene. Moreover, our hunter-gatherer populations show a tendency towards slightly older and stronger growth (approximately 41 thousand years ago, approximately 13-fold) than our food-producing populations (approximately 31 thousand years ago, approximately 7-fold). These dates are concurrent with the appearance of the Late Stone Age in Africa, supporting the hypothesis that population growth played a significant role in the evolution of Late Pleistocene human cultures.

Multiplexed screening assay for mRNA combining nuclease protection with luminescent array detection.

The principles and performance are described for the ArrayPlate mRNA assay, a multiplexed mRNA assay for high-throughput and high-content screening and drug development. THP-1 monocytes grown and subjected to compound treatments in 96-well plates were subjected to a multiplexed nuclease protection assay in situ. The nuclease protection assay destroyed all cell-derived mRNA, but left intact stoichiometric amounts of 16 target-specific oligonucleotide probes. Upon transfer of processed cell lysates to a microplate that contained a 16-element oligonucleotide array at the bottom of each well, the various probe species were separated by immobilization at predefined elements of the array. Quantitative detection of array-bound probes was by enzyme-mediated chemiluminescence. A high-resolution charge-coupled device imager was used for the simultaneous readout of all 1536 array elements in a 96-well plate. For the measurement of 16 genes in samples of 25000 cells, the average standard deviation from well to well within a plate was 8.6% of signal intensity and was 10.8% from plate to plate. Assay response was linear and reproducibility was constant for all detected genes in samples ranging from 1000 to 50000 cells. When THP-1 monocytes were differentiated with phorbol ester and subsequently activated with bacterial lipopolysaccharide that contained different concentrations of dexamethasone, dose-dependent effects of dexamethasone on the mRNA levels of several genes were observed.