Lineage-associated Human Divergently-paired Genes Exhibit Structural and Regulatory Characteristics.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Divergently-paired genes (DPGs) form minimal co-transcriptional units, comprising over 10% of human genes.
• Vertebrate DPGs demonstrate significant conservation compared to invertebrate counterparts.
• Key questions address conserved DPGs across vertebrates, promoter sequence sharing, and human DPG distribution and function in primates.

Purpose of the Study:

• To identify conserved DPGs across vertebrate species, focusing on mammals and primates.
• To investigate the mechanistic and stringent sequence sharing of paired promoters in DPGs.
• To analyze the distribution and biological consequences of human DPGs across primate lineages.

Main Methods:

• Comparative genomics analysis of human DPGs against primate, mammal, avian, and fish genomes.
• Assessment of inter-transcription start site (inter-TSS) distances and their impact on gene co-expression.
• Analysis of human DPGs in European (T2T-CHM13) and Chinese (T2T-YAO) reference genomes.

Main Results:

• 1399 human DPGs identified; conservation observed in 1136 (primates), 1118 (mammals), 925 (avians), and 830 (fish).
• DPGs are functionally enriched in protein-DNA interactions and cell cycle synchronization, with lineage-specific associations.
• Inter-TSS distance influences co-expression strength and disparity; primate DPGs show diversification and involvement in neural development.
• 55 and 357 DPGs were unique to T2T-CHM13 and T2T-YAO human genomes, respectively.

Conclusions:

• DPGs exhibit significant cross-vertebrate conservation, with notable enrichment in mammals and primates.
• Gene co-expression and functional roles are influenced by inter-TSS distances and lineage.
• Human DPGs display evolutionary diversification, particularly in neural development, and population-specific variations.