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Information about genetic structure and historical demography of natural populations is central to understanding how natural selection changes genomes. Drosophila ananassae is a widespread species occurring in geographically isolated or partially isolated populations and provides a unique opportunity to investigate population structure and molecular variation. We assayed microsatellite repeat-length variation among 13 populations of D. ananassae to assess the level of structure among the populations and to make inferences about their ancestry and historic biogeography. High levels of genetic structure are apparent among all populations, particularly in Australasia and the South Pacific, and patterns are consistent with the hypothesis that the ancestral populations are from Southeast Asia. Analysis of population structure and use of F-statistics and Bayesian analysis suggest that the range expansion of the species into the Pacific is complex, with multiple colonization events evident in some populations represented by lineages that show no evidence of recent admixture. The demographic patterns show isolation by distance among populations and population expansion within all populations. A morphologically distinct sister species, D. pallidosa, collected in Malololelei, Samoa, appears to be more closely related to some of the D. ananassae populations than many of the D. ananassae populations are to one another. The patterns of genotypic diversity suggest that many of the individuals that we sampled may be morphologically indistinguishable nascent species.

Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While recent progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila simulans and D. mauritiana. We mapped at least seven QTL affecting discrimination of D. mauritiana females against D. simulans males, three QTL affecting D. simulans male traits against which D. mauritiana females discriminate, and six QTL affecting D. mauritiana male traits against which D. simulans females discriminate. QTL affecting sexual isolation act additively, are largely different in males and females, and are not disproportionately concentrated on the X chromosome: The QTL of greatest effect are located on chromosome 3. Unlike the genetic components of postzygotic isolation, the loci for prezygotic isolation do not interact epistatically. The observation of a few QTL with moderate to large effects will facilitate positional cloning of genes underlying sexual isolation.

Prezygotic mating isolation has been a major interest of evolutionary biologists during the past several decades because it is likely to represent one of the first stages in the transition from populations to species. Mate discrimination is one of the most commonly measured forms of prezygotic isolation and appears to be relatively common among closely related species. In some cases, it has been used as a measure to distinguish populations from subspecies, races, and sister species, yet the influences of various evolutionary mechanisms that may generate mate discrimination are largely unknown. In this study, we measured the level and pattern of mate discrimination among 18 populations of a cosmopolitan drosophilid species, Drosophila ananassae, from throughout its geographical range and its sister species, Drosophila pallidosa, which has a restricted geographical distribution in the South Pacific Islands. In addition, we measured genetic differentiation between all 18 populations using mitochondrial DNA polymorphism data. Mate discrimination varies considerably throughout the species range, being higher among populations outside the ancestral Indonesian range, and highest in the South Pacific. Our results suggest that colonization and genetic differentiation may have an influence on the evolutionary origin of mate discrimination. Our phylogeographical approach clarifies the ancestral relationships of several populations from the South Pacific that show particularly strong mate discrimination and suggests that they may be in the early stages of speciation. Furthermore, both the genetic and behavioral results cast doubt on the status of D. pallidosa as a good species. [ABSTRACT FROM AUTHOR]

A genome-wide scan performed in 638 African American (AA) sibling pairs with type 2 diabetes (T2DM) from 247 families revealed evidence for linkage on chromosome 6q24-27 (LOD 2.26 at 163.5 cM). A dense SNP map was constructed across the 14 Mb LOD-1 interval, We selected 768 SNPs in high priority candidate genes, bin tagSNPs (bins with threshold linkage disequilibrium score r² ≥ 0.8); and to provide physical map coverage in regions of low LD. Illumina Genotyping Services (Illumina Inc., San Diego, CA) performed the genotyping, yielding 754 SNPs successfully genotyped in 294 AA cases with T2DM and end-stage renal disease (T2DM-ESRD), 311 AA controls without a known diabetes diagnosis, 39 European American controls and 45 Yoruba Nigerian samples. One hundred thirty-eight SNPs (18.3%) showed nominal evidence of association (P ≤ 0.05) in one or more of tests of association: allelic, overall genotypic, dominant, additive, or recessive genotypic models, or 2-SNP haplotypic analyses. One hundred thirty-seven SNPs were successfully genotyped in an independent population of 286 AA T2DM-ESRD cases and 288 AA controls. A 2-SNP "risk" haplotype (5.7% in cases, 2.6% in controls; OR 2.26, P=0.05 in the first case-control set and 6.3% in cases, 2.4% in controls; OR 2.73, P=0.02 in the second case-control set) was detected in the parkin (PARK2) gene. Two SNPs in an intergenic region show consistent genotypic association with T2DM-ESRD (additive model P = 0.013 and P=0.046; recessive P= 0.0005 and P=0.013; dominant P= 0.037 and P=0.009) in both our first and second case-control sets respectively. These results provide evidence of T2DM susceptibility variants on chromosome 6q24-27 in an AA population. ADA-Funded Research [ABSTRACT FROM AUTHOR]

The engulfment and cell motility 1 (ELMO1) gene, located on chromosome 7p14.2-14.1, is a strong functional and positional candidate gene that has previously been associated with type 2 diabetes mellitus (T2DM)-associated nephropathy in a Japanese cohort. Three hundred-one HapMap and 10 candidate SNPs were successfully genotyped in 577 African American (AA) T2DM patients with end-stage renal disease (ESRD), 596 AA controls without a current diabetes diagnosis or kidney disease, 39 European American controls and 45 Yoruban Nigerian samples, with an average density of 1 SNP every 2kb. Of the 311 SNPs, 22 (7.1%) and 21 (6.4%) were inconsistent with Hardy Weinberg Equilibrium (HWE) proportions (P ≤ 0.05). Two SNPs deviated from HWE in both cases and controls, due to an excess of homozygotes. Using the four gamete method of block definition of Haploview, extending the block if pairwise D' ≥ 0.8, 64 and 67 blocks, respectively, were detected across the gene in the AA cases and controls. Eighty one SNPs (26%) showed suggestive evidence of association (P ≤ 0.05) in one or more tests of association: allelic, overall genotypic, dominant, additive, or recessive genotypic models, allelic, 2- and 3-SNP haplotypic analyses. Haplotype analysis revealed 11 overlapping 2-SNP haplotypes containing a total of 22 independent SNPs spanning intron 13 that were associated with susceptibility to T2DM-ESRD (P ≤ 0.05). Eight of the 22 SNPs were found to be singly associated with T2DM-ESRD. Admixture adjustments for the positive associations will be performed using data generated by analyzing 70 ancestry informative markers. These results confirm the previous ELMO1 gene association in T2DM-associated nephropathy, extending the observation to T2DM-ESRD in the high risk AA population. ADA-Funded Research [ABSTRACT FROM AUTHOR]

Evidence for linkage in a genome-wide scan for type 2 diabetes mellitus (T2DM) in African Americans (AA) was observed at 6q24-27, an interval containing the gene encoding estrogen receptor α (ESR1). One hundred thirty-one SNPs, spanning nearly 462 kb, located in the coding and flanking regions of ESR1 were genotyped in 577 AA individuals with T2DM and End Stage Renal Disease (ESRD) and 596 AA without a diagnosis for T2DM. Haplotypic association and genotypic association for dominant, additive, and recessive models were tested by calculating a x² statistic and corresponding P value using the program SNPGWA. Twenty eight SNPs show evidence for association (P≤0.05) with T2DM-ESRD in one or more genotypic model. Nineteen of the twenty eight associated SNPs cluster together and are located in an 85 kb region of the gene. Stratification based on gender reveals evidence for association with 33 SNPs in females (N= 352 Cases; 306 Controls) and 8 SNPs in males (N= 225 Cases; 290 Controls). The association results appear to be influenced predominately by our female subjects, suggesting a possible sexual dimorphism with ESR1 and T2DM-ESRD in our AA population. Our results confirm a positive association with T2DM-ESRD in AA in the intron 1-intron 2 region (rs1033182; P= 0.025, dominant model) and provides additional evidence for association in the intron 5-intron 6 region. We believe that we have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and or diabetic nephropathy. ADA-Funded Research [ABSTRACT FROM AUTHOR]