Daryn A. Stover

Contrasting patterns of Y chromosome and mtDNA variation in Africa: Evidence for sex-biased demographic processes

To investigate associations between genetic, linguistic, and geographic variation in Africa, we type 50 Y chromosome SNPs in 1122 individuals from 40 populations representing African geographic and linguistic diversity. We compare these patterns of variation with those that emerge from a similar analysis of published mtDNA HVS1 sequences from 1918 individuals from 39 African populations. For the Y chromosome, Mantel tests reveal a strong partial correlation between genetic and linguistic distances (r=0.33, P=0.001) and no correlation between genetic and geographic distances (r=−0.08, P>0.10). In contrast, mtDNA variation is weakly correlated with both language (r=0.16, P=0.046) and geography (r=0.17, P=0.035). AMOVA indicates that the amount of paternal among-group variation is much higher when populations are grouped by linguistics (ΦCT=0.21) than by geography (ΦCT=0.06). Levels of maternal genetic among-group variation are low for both linguistics and geography (ΦCT=0.03 and 0.04, respectively). When Bantu speakers are removed from these analyses, the correlation with linguistic variation disappears for the Y chromosome and strengthens for mtDNA. These data suggest that patterns of differentiation and gene flow in Africa have differed for men and women in the recent evolutionary past. We infer that sex-biased rates of admixture and/or language borrowing between expanding Bantu farmers and local hunter-gatherers played an important role in influencing patterns of genetic variation during the spread of African agriculture in the last 4000 years.

Comparative Vertebrate Evolutionary Analyses of Type I Collagen: Potential of COL1a1 Gene Structure and Intron Variation for Common Bone-Related Diseases

Collagen type I alpha 1 (COL1a1), which encodes the primary subunit of type I collagen, the main structural and most abundant protein in vertebrates, harbors hundreds of mutations linked to human diseases like osteoporosis and osteogenesis imperfecta. Previous studies have attempted to predict the phenotypic severity associated with type I collagen mutations, yet an evolutionary analysis that compares historical and recent selective pressures, including across noncoding regions, has never been conducted. Here, we use a comparative genomic and species evolutionary analysis representing ∼450 My of vertebrate history to investigate functional constraints associated with both exons and introns of the >17-kb COL1a1 gene. We find that although the COL1a1 amino acid sequence is highly conserved, there are both spatial and temporal signatures of varying selective constraint across protein domains. Furthermore, sites of high evolutionary constraint significantly correlate with the location of disease-associated mutations, the latter of which also cluster with respect to specific severity classes typically categorized in clinical studies. Finally, we find that COL1a1 introns are significantly short in length with high GC content, patterns that are shared across highly diverged vertebrates, and which may be a signature of strong stabilizing selection for high COL1a1 gene expression. In conclusion, although previous studies focused on COL1a1 coding regions, the current results implicate introns as areas of high selective constraint and targets of bone-related phenotypic variation. From a broader perspective, our comparative evolutionary approach provides further resolution to models predicting mutations associated with bone-related function and disease severity.

Genetic Structure Among 38 Populations from the United States Based on 11 U.S. Core Y Chromosome STRs

ABSTRACT: A DNA database consisting of the 11 Y chromosome short‐tandem‐repeat (Y‐STR) recommended by the Scientific Working Group on DNA Analysis Methods is constructed for 2517 individuals from 38 populations in the United States. The population samples derive from five ethnic groups currently living in 10 states. A multidimensional scaling (MDS) plot places the populations into four discrete clusters (African Americans (AA), European Americans (EA), Hispanic Americans (HA), and Asian Americans (SA)) and one dispersed cluster of Native Americans. An analysis of molecular variance (AMOVA) indicates that a large proportion of the total genetic variance is partitioned among ethnic groups (24.8%), whereas only a small amount (1.5%) is found among‐populations within ethnic groups. Separate AMOVA analyses within each ethnic group show that only the NA sample contains statistically significant among‐population variation. Pair wise population differentiation tests do uncover heterogeneity among EA and among HA populations; however, this is due to only a single sample within each group. The analyses support the creation of AA, EA, HA, and Asian American databases in which samples from different geographic regions within the United States are pooled. We recommend that separate databases be constructed for different NA groups.

Positive selection on human gamete-recognition genes

Coevolution of genes that encode interacting proteins expressed on the surfaces of sperm and eggs can lead to variation in reproductive compatibility between mates and reproductive isolation between members of different species. Previous studies in mice and other mammals have focused in particular on evidence for positive or diversifying selection that shapes the evolution of genes that encode sperm-binding proteins expressed in the egg coat or zona pellucida (ZP). By fitting phylogenetic models of codon evolution to data from the 1000 Genomes Project, we identified candidate sites evolving under diversifying selection in the human genes ZP3 and ZP2. We also identified one candidate site under positive selection in C4BPA, which encodes a repetitive protein similar to the mouse protein ZP3R that is expressed in the sperm head and binds to the ZP at fertilization. Results from several additional analyses that applied population genetic models to the same data were consistent with the hypothesis of selection on those candidate sites leading to coevolution of sperm- and egg-expressed genes. By contrast, we found no candidate sites under selection in a fourth gene (ZP1) that encodes an egg coat structural protein not directly involved in sperm binding. Finally, we found that two of the candidate sites (in C4BPA and ZP2) were correlated with variation in family size and birth rate among Hutterite couples, and those two candidate sites were also in linkage disequilibrium in the same Hutterite study population. All of these lines of evidence are consistent with predictions from a previously proposed hypothesis of balancing selection on epistatic interactions between C4BPA and ZP3 at fertilization that lead to the evolution of co-adapted allele pairs. Such patterns also suggest specific molecular traits that may be associated with both natural reproductive variation and clinical infertility.