At what spatial scale(s) do mammals respond to urbanization?

Spatial scale is fundamental in understanding species–landscape relationships because species’ responses to landscape characteristics typically vary across scales. Nonetheless, such scales are often unidentified or unreliably predicted by theory. Many landscapes worldwide are urbanizing, yet the spatial scaling of species’ responses to urbanization is poorly understood. We investigated the spatial scaling of urbanization effects on a community of 15 mammal species using ~60 000 wildlife detections collected from a constellation of 207 camera traps across an extensive urban park system. We embedded a bivariate Gaussian kernel in hierarchical multi-species models to determine two scales of effect (a scale of maximal effect and a broader scale of cumulative landscape effect) for two biological responses (occupancy and site visit frequency) across two seasons (winter and summer) for each species. We then assessed whether scales of effect varied according to theoretical predictions associated with biological responses and species traits (body size and mobility). Scales of effect ranged from < 50 m to > 9000 m and varied among species, but not as predicted by theory. Species’ occupancy generally showed a weak response to urbanization and the scale of this effect was both highly uncertain and consistent across species. We did not detect any relationship between scales of effect and species’ body size or mobility, nor was there any evident pattern of scaling across biological response or seasons. These results imply that 1) urbanization effects on mammals manifest across a very broad spectrum of spatial scales, and 2) current theories that a priori predict the scale at which urbanization affects mammals may be of limited use within a given system. Overall, this study suggests that developing general theory regarding the scaling of species–landscape relationships requires additional empirical work conducted across multiple species, systems and timescales.     

QUANTITATIVE GENETICS OF HETEROCHRONY

A model of quantitative-genetic variation in developmental processes is introduced and analyzed. The model is of a bifurcating sequence of events in which traits develop from the same tissue until a transition occurs, after which they develop partially independently. Genetic and environmental variation in both the rates of tissue growth and in the timing of transitions is considered. The model shows how genetic variation in developmental parameters governs variation and covariation in phenotypic traits and how selection on the phenotype alters the distributions of developmental parameters. Particular attention is paid to the conditions under which selection will lead to changes in the average times of developmental events.     

Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates

The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cis-regulatory regions play a dominant role in phenotypic evolution.     

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.     

Rare and common regulatory variation in population-scale sequenced human genomes

Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs) when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs) discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.     

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene–environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10⁻⁹. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.     

Variants in TF and HFE Explain ∼40% of Genetic Variation in Serum-Transferrin Levels

Only a small proportion of genetic variation in complex traits has been explained by SNPs from genome-wide association studies (GWASs). We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g., hemochromatosis) and deficiency (e.g., anemia) conditions. We performed two GWASs on samples of Australians of European descent. In the first GWAS, 411 adolescent twins and their siblings were genotyped with 100K SNPs. rs1830084, 10.8 kb 3′ of TF, was significantly associated with serum transferrin (p total association test = 1.0 × 10⁻⁹; p within-family test = 2.2 × 10⁻⁵). In the second GWAS on an independent sample of 459 female monozygotic (MZ) twin pairs genotyped with 300K SNPs, we found rs3811647 (within intron 11 of TF, HapMap CEU r² with rs1830084 = 0.86) was significantly associated with serum transferrin (p = 3.0 × 10⁻¹⁵). In the second GWAS, we found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin. The three variants in TF (rs3811647, rs1799852 and rs2280673) plus the HFE C282Y mutation explained ~40% of genetic variation in serum transferrin (p = 7.8 × 10⁻²⁵). These findings are potentially important for our understanding of iron metabolism and of regulation of hepatic protein secretion, and also strongly support the hypothesis that the genetic architecture of some endophenotypes may be simpler than that of disease.