Ancestral Similarity Research Articles

Abstract 6117: Characterizing cancer patterns in Okinawan vs. mainland Japanese Americans: The Multiethnic Cohort

Abstract Differences in chronic disease rates have been documented in Japan between Okinawa and mainland Japan. Limited data exist on whether these differences are also present in Okinawans and mainland Japanese who have migrated to the US. We used genotyped genome-wide association study data from the Multiethnic Cohort Study (MEC) to identify Japanese Americans of Okinawan or mainland ancestral similarity, and to investigate these two groups for differences in baseline chronic disease risk factors and for incidence of the four most common cancers during follow-up after blood draw. Cancer cases were identified via linkage to state cancer registries. Principal component analysis followed by uniform manifold approximation and projection (UMAP) was run using 15,678 single nucleotide polymorphisms among the 24,484 MEC Japanese Americans with blood samples. The Okinawan cluster was confirmed by labeling male MEC participants with Okinawan surnames on UMAP plots. Hazard ratios (HR), 95% confidence intervals (CI), and two-sided p-values were reported for Cox proportional hazards models, comparing cancer incidence between Okinawan and mainland Japanese individuals. The Okinawan cluster included 3,649 individuals (15% of the MEC Japanese Americans) and the mainland Japanese cluster included 19,611 individuals (80% of the MEC Japanese Americans). Small clusters of part-Okinawan and/or part-mainland Japanese (5% of the MEC Japanese Americans) were not included in the analysis. Ninety-six percent of Okinawan Americans and 94% of mainland Japanese Americans in MEC were born in the US. Okinawans were more likely to have a higher body mass index and daily alcohol intake, and less likely to be a current or former smoker, compared to mainland Japanese (all p-values<0.05). Post-menopausal Okinawan women were significantly more likely to be diagnosed with breast cancer (age-adjusted HR=1.39, 95% CI=1.10-1.75) compared to post-menopausal mainland Japanese women. This association was not modified by adjusting for additional known breast cancer risk factors (HR=1.36, 95% CI=1.07-1.73). Okinawans were also less likely to be diagnosed with lung cancer (HR=0.75, 95% CI=0.58-0.98); however, this association was no longer significant when adjusting for known risk factors, including smoking history (HR=0.82, 95% CI=0.62-1.07). There were no significant differences in risk of colorectal or prostate cancer between Okinawan and mainland Japanese individuals. Our results in this US-based sample are consistent with recent trends of higher breast cancer and lower lung cancer age-adjusted incidence rates reported from Japan for the Okinawan prefecture compared to mainland prefectures. Investigating reasons for the observed breast cancer risk difference may identify new risk factors for this disease in the Okinawan and other populations. Citation Format: Samantha A. Streicher, Song-Yi Park, Charleston W. Chiang, Xin Sheng, David Bogumil, David V. Conti, Christopher A. Haiman, Lynne R. Wilkens, Loic Le Marchand. Characterizing cancer patterns in Okinawan vs. mainland Japanese Americans: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6117.

Multi‐Ancestry Genetics for Alzheimer’s Disease: Alzheimer’s Disease Genetics Consortium

AbstractBackgroundAlzheimer’s disease (AD) affects individuals of all races and ethnicities, yet large‐scale genetic research to compare genetic makeups for risk or protection of AD between multi‐ancestry datasets is limited. The Alzheimer’s Disease Genetics Consortium (ADGC) assembled the largest multi‐ancestry dataset including 56,241 subjects from non‐Hispanic Whites (NHW), African Americans (AA), Hispanics (HI), and East Asians (EAS) to understand ancestral similarities and differences in genetic risk and protective variants for AD.MethodWe established a Steering Committee with 5 members, 4 main Workgroups including Primary Meta‐Analysis, Follow‐Up Analysis, Secondary Analysis, and Method Evaluation, and 3 affiliated Workgroups consisting of Phenotype Harmonization, Imputation Development, and genome‐wide association study (GWAS)/whole genome sequencing (WGS) Integration. A new computing infrastructure was developed for shared analytic space on Amazon Web Services (AWS), where all members from different institutes accessed to genetic and phenotypic data and conducted analysis under the master analysis plan with centrally developed pipelines and scripts. We conducted ancestry‐specific GWAS using single nucleotide polymorphisms (SNPs) for AD, cross‐ancestry meta‐analysis of 4 ancestry GWASs, fine‐mapping for allelic heterogeneity in known and novel loci for AD, and pathway analysis.ResultWe confirmed 12 known including APOE ɛ4 and ɛ2 variants and identified 2 novel loci for AD in cross‐ancestry meta‐analysis with P<5.4×10−8. African and Asian ancestry subjects displayed greater heterogeneity in effect sizes and significant levels with the previously known AD loci for AD. Ancestry‐specific fine‐mapping indicated presence of potential distinct causal variants across different ancestry groups from multiple known AD loci. Two APOE alleles had greatest effect sizes among East Asians compared to others (EAS>NHW>AA>HI), while we failed to observe significant association signals with AD in SHARPIN and TREM2 regions from African Americans. Of two novel loci, the association signal in the LRRC4C‐API5 region was contributed from all four ancestry groups; in contrast, the signal in the LHX5‐AS1‐RBM19 region was predominantly from Hispanics.ConclusionGenetic risk profiling in multi‐ancestry datasets provided unique opportunity to understand ancestry‐specific and cross‐ancestry genetic risk factors for AD. Further evaluation of these established and novel loci for AD by integrating GWAS and WGS data from ADSP is underway

Cultures of Cultural Globalization: How National Repertoires and Political Ideologies Affect Literary and Artistic Circulation

While prior research foregrounds the economic and political conditions that shape cultural globalization, we focus on the effects of culture. We argue that diffusion itself is a cultural practice, and that two types of cultural schemas – ways of conceptualizing national belonging, on the one hand, and geopolitical ideologies, on the other – shape the people, policies, and infrastructures actors deploy to insert their cultural products into the global art and literary worlds. Based on fieldwork in Argentina, South Korea, and Lebanon, we show how two forms of trans-border nationalism – those that incorporate the diaspora based on ethnic or ancestral similarity, and those that incorporate regional neighbors based on common civic norms – are mobilized to circulate art and literature internationally. Who participates in these diasporic and regional networks, however, depends on diffusers’ ideological commitments. We identify two types of aspirational visions for a global (art) world order, which influence which people and institutions cultural makers and managers draw on to diffuse art and literature: a reformative vision, in which the core institutions in traditional centers of power maintain their centrality but become more inclusive of creators from historically underrepresented countries, and a transformative vision, in which the global art and literary world are restructured and power redistributed via new nodes and circuits that circumvent these traditional centers.

Deconstructing the long-standing a priori assumption that serial homology generally involves ancestral similarity followed by anatomical divergence.

It has long been assumed that serial homologues are ancestrally similar-polysomerism resulting from a "duplication" or "repetition" of forms-and then often diverge-anisomerism, for example, as they become adapted to perform different tasks as is the case with the forelimb and hind limbs of humans. However, such an assumption, with crucial implications for comparative, evolutionary, and developmental biology, and for evolutionary developmental biology, has in general not really been tested by a broad analysis of the available empirical data. Perhaps not surprisingly, more recent anatomical comparisons, as well as molecular knowledge of how, for example, serial appendicular structures are patterned along with different anteroposterior regions of the body axis of bilateral animals, and how "homologous" patterning domains do not necessarily mark "homologous" morphological domains, are putting in question this paradigm. In fact, apart from showing that many so-called "serial homologues" might not be similar at all, recent works have shown that in at least some cases some "serial" structures are indeed more similar to each other in derived taxa than in phylogenetically more ancestral ones, as pointed out by authors such as Owen. In this article, we are taking a step back to question whether such assumptions are actually correct at all, in the first place. In particular, we review other cases of so-called "serial homologues" such as insect wings, arthropod walking appendages, Dipteran thoracic bristles, and the vertebrae, ribs, teeth, myomeres, feathers, and hairs of chordate animals. We show that: (a) there are almost never cases of true ancestral similarity; (b) in evolution, such structures-for example, vertebra-and/or their subparts-for example, "transverse processes"-many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism.

Competition and hybridization drive interspecific territoriality in birds

Costly interactions between species that arise as a by-product of ancestral similarities in communication signals are expected to persist only under specific evolutionary circumstances. Territorial aggression between species, for instance, is widely assumed to persist only when extrinsic barriers prevent niche divergence or selection in sympatry is too weak to overcome gene flow from allopatry. However, recent theoretical and comparative studies have challenged this view. Here we present a large-scale, phylogenetic analysis of the distribution and determinants of interspecific territoriality. We find that interspecific territoriality is widespread in birds and strongly associated with hybridization and resource overlap during the breeding season. Contrary to the view that territoriality only persists between species that rarely breed in the same areas or where niche divergence is constrained by habitat structure, we find that interspecific territoriality is positively associated with breeding habitat overlap and unrelated to habitat structure. Furthermore, our results provide compelling evidence that ancestral similarities in territorial signals are maintained and reinforced by selection when interspecific territoriality is adaptive. The territorial signals linked to interspecific territoriality in birds depend on the evolutionary age of interacting species, plumage at shallow (within-family) timescales, and song at deeper (between-family) timescales. Evidently, territorial interactions between species have persisted and shaped phenotypic diversity on a macroevolutionary timescale.

Genome Data Exploration Using Correspondence Analysis.

Recent developments of sequencing technologies that allow the production of massive amounts of genomic and genotyping data have highlighted the need for synthetic data representation and pattern recognition methods that can mine and help discovering biologically meaningful knowledge included in such large data sets. Correspondence analysis (CA) is an exploratory descriptive method designed to analyze two-way data tables, including some measure of association between rows and columns. It constructs linear combinations of variables, known as factors. CA has been used for decades to study high-dimensional data, and remarkable inferences from large data tables were obtained by reducing the dimensionality to a few orthogonal factors that correspond to the largest amount of variability in the data. Herein, I review CA and highlight its use by considering examples in handling high-dimensional data that can be constructed from genomic and genetic studies. Examples in amino acid compositions of large sets of species (viruses, phages, yeast, and fungi) as well as an example related to pairwise shared orthologs in a set of yeast and fungal species, as obtained from their proteome comparisons, are considered. For the first time, results show striking segregations between yeasts and fungi as well as between viruses and phages. Distributions obtained from shared orthologs show clusters of yeast and fungal species corresponding to their phylogenetic relationships. A direct comparison with the principal component analysis method is discussed using a recently published example of genotyping data related to newly discovered traces of an ancient hominid that was compared to modern human populations in the search for ancestral similarities. CA offers more detailed results highlighting links between modern humans and the ancient hominid and their characterizations. Compared to the popular principal component analysis method, CA allows easier and more effective interpretation of results, particularly by the ability of relating individual patterns with their corresponding characteristic variables.

Phylogenetic Analysis of Aphaenogaster Supports the Resurrection of Novomessor (Hymenoptera: Formicidae)

ABSTRACT The ant genus Aphaenogaster Mayr is an ecologically diverse group that is common throughout much of North America. Aphaenogaster has a complicated taxonomic history due to variability of taxonomic characters. Novomessor Emery was previously synonymized with Aphaenogaster, which was justified by the partial mesonotal suture observed in Aphaenogaster ensifera Forel. Previous studies using Bayesian phylogenies with molecular data suggest Aphaenogaster is polyphyletic. Convergent evolution and retention of ancestral similarities are two major factors contributing to nonmonophyly of Aphaenogaster. Based on 42 multistate morphological characters and five genes, we found Novomessor more closely related to Veromessor Forel and that this clade is sister to Aphaenogaster. Our results confirm the validity of Novomessor stat. r. as a separate genus, and it is resurrected based on the combination of new DNA, morphological, behavioral, and ecological data.

ECOD: an evolutionary classification of protein domains.

Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or “fold”). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

Low Frequency Variants, Collapsed Based on Biological Knowledge, Uncover Complexity of Population Stratification in 1000 Genomes Project Data

Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses.

Hypothesis testing in evolutionary developmental biology: a case study from insect wings.

Developmental data have the potential to give novel insights into morphological evolution. Because developmental data are time-consuming to obtain, support for hypotheses often rests on data from only a few distantly related species. Similarities between these distantly related species are parsimoniously inferred to represent ancestral aspects of development. However, with limited taxon sampling, ancestral similarities in developmental patterning can be difficult to distinguish from similarities that result from convergent co-option of developmental networks, which appears to be common in developmental evolution. Using a case study from insect wings, we discuss how these competing explanations for similarity can be evaluated. Two kinds of developmental data have recently been used to support the hypothesis that insect wings evolved by modification of limb branches that were present in ancestral arthropods. This support rests on the assumption that aspects of wing development in Drosophila, including similarities to crustacean epipod patterning, are ancestral for winged insects. Testing this assumption requires comparisons of wing development in Drosophila and other winged insects. Here we review data that bear on this assumption, including new data on the functions of wingless and decapentaplegic during appendage allocation in the red flour beetle Tribolium castaneum.

A COMPARISON OF CHROMOSOME KNOB FREQUENCIES BETWEEN SYMPATRIC AND ALLOPATRIC POPULATIONS OF TEOSINTE AND MAIZE

Unrestricted gene flow would be expected to lead to similar chromosome knob frequencies in sympatric populations of maize and teosinte. Chi‐square tests were therefore used to compare chromosome knob frequencies of 45 collections of Mexican teosinte, grouped according to six geographic regions, with sympatric and allopatric populations of maize. Comparisons of knob frequencies between sympatric and allopatric populations within each region produced an initial classification for each knob‐forming position. Further comparisons for each knob position over all regions, led to an interpretation of results for sympatric populations of maize and teosinte in terms of gene flow, selection, differentiation, ancestral similarities, and ancestral differences. Within regions, a high number of knob positions suggesting gene flow was associated with a low number of knob positions suggesting recent differentiation, and vice versa. It is suggested that the teosinte populations most likely to represent unique sources of germplasm are those most susceptible to future genetic erosion by maize. These relationships may represent a general model applicable to a number of crop plants and associated weed races.