Understanding How Stochasticity Impacts Reconstructions of Recent Species Divergent History.

Molecular phylogenetic studies are complicated by the fact that differentiation between orthologous gene copies is determined by two stochastic process–lineage sorting (coalescent) and mutational processes. The former could lead to discrepancies between the species divergent history and genealogies, while the later could result in differences between genealogies and estimated gene trees. Only recently has the idea of incorporating the coalescent process into species-tree estimation been applied in empirical phylogenetics. My thesis focuses on examining the impacts of these two stochasticities on reconstructing recent species divergent histories where incomplete lineage sorting is prevalent. Using simulated data, the effect of mutation variance is re-evaluated on accuracy of species-tree estimates with different methods, ranging from the simplest “democratic voting”, to the Maximum-likelihood method includes the branch length information, and the implications in terms of sampling design, methods for gene-tree and species-tree estimation, are discussed in Chapter II&III. While future phylogenetic studies will benefit from the new species-tree estimation methods, it is not clear is the extent to which species relationships estimated with data and methods that predate these developments are robust. I proposed a parametric bootstrap species tree (PBST) approach to assess the reliability of past phylogenetic studies in which the stochastic lineage sorting processes were overlooked, and applied the approach as a meta-analysis of east African cichlid phylogenies in Chapter IV. Another problem for empirical phylogenetic studies to applying species-tree estimation is to having a multi-locus sequencing dataset, Next-generation sequencing (NGS) combined with Reduce Representation Library technique has the premise but concerns exist about whether the high NGS error rates are amenable for directly use for phylogenetic analysis. The use of NGS as primary data for reconstructing the divergent history was explored of four montane grasshopper species in Chapter IV, and parametric simulation was used to three possible sources of uncertainty in the estimated species tree: the true species divergent history, sequencing errors and error correction method. Possible improvement on sampling design and the methodological developments needed for future studies are discussed. The last chapter explored the use of gene divergent history combined with geographic information to infer speciation models.Ph.D.Ecology and Evolutionary BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91486/1/huatengh_1.pd

On a taxonomic feature that has been overestimated in classification practice: an integrative taxonomic revision of Stephoblemmus Saussure, 1877 based on morphology and molecular phylogeny (Orthoptera: Grylloidea; Gryllidae; Gryllinae)

The hemispherical head is prevalent in Gryllinae crickets, so the rare crickets that have a unique form of head will be extremely unusual. In previous studies, this special feature can be one of the important features to distinguish and identify these crickets. But does this particular head shape truly reflect a clear-cut taxonomic relationship? The species of the genus Loxoblemmus have a typical truncate head; species of the genus Stephoblemmus have a more exaggerated truncate head, with the frontal end even extending into a lamellar. The genus Mitius is relatively unusual in that species of this genus have both globose or truncate heads. How are these species related? Does the cephalic shape perfectly reflect the natural classification of these species? Based on these questions, the study applied species definition and morphological classification to explore the intergeneric and intrageneric species relationships of the genera Mitius, Stephoblemmus, and Loxoblemmus, and derived the following main conclusions: (1) Mitius and Stephoblemmus are related and distinct from Loxoblemmus; (2) Mitius species bear two types of frons (truncated and rounded), but this feature disallows them to be classified as natural groups; (3) one genus synonym and three species synonyms are raised (Mitius Gorochov, 1985 syn. n., Mitius splendens (Shiraki, 1930) syn. n., Mitius eryuanensis Yuan, Xie & Liu, 2021 syn. n. and Mitius brevipennis Yuan, Ma & Gu, 2022 syn. n.), and seven new status combinations are proposed (Stephoblemmus blennus (Saussure, 1877) comb. n., Stephoblemmus castaneus (Chopard, 1937) comb. n., Stephoblemmus enatus Gorochov, 1994 comb. n., Stephoblemmus flavipes (Chopard, 1928) comb. n., Stephoblemmus minor (Shiraki, 1911) comb. n., Stephoblemmus minutulus (Yang & Yang, 1995) comb. n. and Stephoblemmus vaturu (Otte & Cowper, 2007) comb. n.). The studies indicated that frons shapes that appear to be significantly different might not always reflect the correct Gryllinae species relationships and a combination of more taxonomic features and taxonomic techniques is needed often to reveal the true taxonomic relationships

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

coverage

a Perl script for filtering out sequences with no read (coverage draw from a poisson distribution