Genetic composition
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Genetic Composition: Insights from Recent Research
Compositional Heterogeneity in Eukaryotic Genomes
GC Content and Compositional Heterogeneity
The study of eukaryotic genomes reveals significant compositional heterogeneity, particularly in relation to GC content. The compositional heterogeneity index, which measures the average difference in GC content between adjacent windows, shows a strong correlation with GC content across multicellular eukaryotes, regardless of genome size . This heterogeneity is especially pronounced in the human genome, which exhibits high variability both within and between chromosomes, surpassing the predictions of the isochore model .
Isochores and GC-Rich Regions
While all multicellular eukaryotic genomes contain compositionally uniform segments known as isochores, the human genome is unique due to its very high GC regions that exhibit unusually high compositional heterogeneity and contain few long homogeneous segments . GC-poor isochores tend to be longer than GC-rich ones, indicating a complex and heterogeneous nucleotide composition in multicellular organisms .
Microbial Genome Composition
Compositional Variation and Genome Fragment Distinguishability
Microbial genomes also exhibit significant compositional variation, which can be used to distinguish between different genomes. Studies on 774 sequenced microbial genomes show rapid divergence among closely related genomes and convergence of compositional patterns among genomes with similar habitats . Techniques such as support vector machines have been employed to distinguish genome fragments based on their composition, achieving high accuracy in classification .
Factors Influencing Genome Distinguishability
Several factors, including genome reduction, lateral genetic transfer, and habitat convergence, influence the distinguishability of microbial genomes. The positional, compositional, and functional context of a genome fragment plays a crucial role in its correct classification, depending on the taxonomic and ecological similarity of the comparator genome .
Genetic Influence on Body Composition
Heritability and Genotype-Environment Interactions
Body composition is influenced by multiple genetic traits, with studies on twins and family relatives demonstrating high heritability (0.4-0.7) for many traits . Genotype-environment interactions, particularly with diet and activity, also play a significant role in determining body composition . Major genes controlling products like leptin are involved in the regulation of appetite and energy expenditure, impacting conditions such as leanness and obesity .
Potential for Gene Therapy
The identification of novel major genes in various species holds promise for future gene therapy applications to address intractable conditions related to body composition. However, the control of body composition remains challenging due to unfavorable genetic correlations and the complexity of genetically programmed traits .
Genetic Composition of Influenza Vaccine Strains
Recombination and Growth Capacity
The genetic composition of high-yielding influenza vaccine strains, obtained through recombination, includes surface hemagglutinin and neuraminidase antigens from low-yielding parental viruses. The increased growth capacity of these recombinants is associated with genes derived from the high-yielding laboratory strain A/Puerto Rico/8/34, particularly the M gene . However, specific genes or gene combinations responsible for the increased growth capacity have not been identified .
Tissue Composition and Gene Co-Expression
Impact on Genomic Profiling
Variable cellular composition in tissue samples poses challenges for genomic profiling studies. Adjusting for compositional differences is crucial for accurate differential expression estimation between sample types 57. Deconvolution methods, initially developed for separating tumor and stromal signatures, can be applied to mixtures of two cell types to improve co-expression pattern estimation 57.
Deconvolution Methods
Uncorrelated cell-type-specific markers are ideal for deconvoluting expression and co-expression patterns of individual cell types. These methods are beneficial under specific conditions, as demonstrated in both simulated and real data 57.
Genetic Variation and Microbiome Composition
Host Genetic Influence
The composition of the human microbiome varies widely across individuals and is influenced by host genetic variation. Significant associations between host genetic variation and microbiome composition have been identified in multiple body sites, driven by immunity-related pathways . These associations are enriched in genes previously linked to microbiome-related diseases, such as inflammatory bowel disease and obesity .
Evolutionary Implications
Host genomic regions associated with the microbiome exhibit high levels of genetic differentiation among human populations, suggesting possible adaptation to environment-specific microbiomes . This highlights the complex interaction between human genetics and the microbiome in the context of evolution and disease .
Conclusion
The genetic composition of organisms, from eukaryotes to microbes, exhibits significant heterogeneity and variation influenced by multiple factors, including GC content, environmental interactions, and host genetics. Understanding these compositional patterns provides insights into genome evolution, disease mechanisms, and potential therapeutic applications.
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