Quantitative analysis of population-scale family trees with millions of relatives.

Family trees have vast applications in fields as diverse as genetics, anthropology, and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. We collected 86 million profiles from publicly available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of human longevity and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other data sets with our resource.

Multicellularity makes somatic differentiation evolutionarily stable.

Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation.

Spatially Constrained Growth Enhances Conversional Meltdown.

Cells that mutate or commit to a specialized function (differentiate) often undergo conversions that are effectively irreversible. Slowed growth of converted cells can act as a form of selection, balancing unidirectional conversion to maintain both cell types at a steady-state ratio. However, when one-way conversion is insufficiently counterbalanced by selection, the original cell type will ultimately be lost, often with negative impacts on the population's overall fitness. The critical balance between selection and conversion needed for preservation of unconverted cells and the steady-state ratio between cell types depends on the spatial circumstances under which cells proliferate. We present experimental data on a yeast strain engineered to undergo irreversible conversion: this synthetic system permits cell-type-specific fluorescent labeling and exogenous variation of the relative growth and conversion rates. We find that populations confined to grow on a flat agar surface are more susceptible than their well-mixed counterparts to fitness loss via a conversion-induced "meltdown." We then present analytical predictions for growth in several biologically relevant geometries-well-mixed liquid media, radially expanding two-dimensional colonies, and linear fronts in two dimensions-by employing analogies to the directed-percolation transition from nonequilibrium statistical physics. These simplified theories are consistent with the experimental results.

The cis-regulatory system of the tbrain gene: Alternative use of multiple modules to promote skeletogenic expression in the sea urchin embryo.

The genomic cis-regulatory systems controlling regulatory gene expression usually include multiple modules. The regulatory output of such systems at any given time depends on which module is directing the function of the basal transcription apparatus, and ultimately on the transcription factor inputs into that module. Here we examine regulation of the Strongylocentrotus purpuratus tbrain gene, a required activator of the skeletogenic specification state in the lineage descendant from the embryo micromeres. Alternate cis-regulatory modules were found to convey skeletogenic expression in reporter constructs. To determine their relative developmental functions in context, we made use of recombineered BAC constructs containing a GFP reporter and of derivatives from which specific modules had been deleted. The outputs of the various constructs were observed spatially by GFP fluorescence and quantitatively over time by QPCR. In the context of the complete genomic locus, early skeletogenic expression is controlled by an intron enhancer plus a proximal region containing a HesC site as predicted from network analysis. From ingression onward, however, a dedicated distal module utilizing positive Ets1/2 inputs contributes to definitive expression in the skeletogenic mesenchyme. This module also mediates a newly discovered negative Erg input which excludes non-skeletogenic mesodermal expression.