Tissue-Specific Evolution of Protein Coding Genes in Human and Mouse.

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Protein-coding gene evolutionary rates vary, with expression levels being a key driver in yeast but not animals.
• The complexity of factors influencing animal gene evolution necessitates further investigation into tissue-specific expression and indirect correlations.

Purpose of the Study:

• To investigate the relationship between gene evolutionary rates and various parameters, including tissue-specific gene expression and indirect correlations in animals.
• To identify the primary factors driving purifying selection and evolutionary rates across different mammalian tissues.

Main Methods:

• Utilized RNA-seq data from large-scale datasets covering 22 mouse and 27 human tissues.
• Analyzed correlations between gene evolutionary rates, gene expression levels (overall and tissue-specific), GC content, and developmental expression patterns.

Main Results:

• Evolutionary rate showed weak correlation with overall expression levels and breadth across tissues.
• GC content, broad developmental stage expression, and brain tissue expression were strongest predictors of purifying selection.
• Tissue-specific patterns were observed for neutral and positive selection, with rapid evolution in testis and liver attributed to relaxed purifying selection.

Conclusions:

• Gene evolutionary rates in animals are influenced by a complex interplay of factors, with GC content and specific tissue expression (brain, testis, liver) being significant.
• Relaxed purifying selection, rather than positive selection, primarily explains rapid gene evolution in tissues like the testis and liver.