An Evaluation of Function of Multicopy Noncoding RNAs in Mammals Using ENCODE/FANTOM Data and Comparative Genomics

Area of Science:

• Genomics
• Molecular Evolution
• RNA Biology

Background:

• Mammalian genomes show rapid expansion of noncoding RNAs (ncRNAs), including small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs).
• The functional significance of these ncRNA copy-number expansions remains largely unknown, with potential for both adaptive and neutral evolutionary processes.
• Large-scale genomic projects like ENCODE and FANTOM provide expression data but are viewed skeptically by molecular evolutionists regarding functional insights.

Purpose of the Study:

• To investigate the functional evidence for recent mammalian copy-number expansions of six ancient RNA families involved in splicing and rRNA maturation.
• To apply molecular evolution criteria to assess the biological significance of these ncRNA expansions.

Main Methods:

• Utilized data from ENCODE and FANTOM projects alongside molecular evolution analyses.
• Assessed evidence for function using criteria including sequence and structural conservation, genomic synteny, transposition evidence, and species-specific expression patterns.
• Applied these criteria to six ancient RNA families with recent copy-number expansions in mammals.

Main Results:

• Only a small subset of the examined ncRNA loci displayed strong evidence for biological function.
• The majority of ncRNA loci examined could not be distinguished from having no function, failing to reject the null hypothesis.
• The study highlights the difficulty in assigning function to newly expanded ncRNA families.

Conclusions:

• The functional significance of most recent ncRNA copy-number expansions in mammals is not strongly supported by current evidence.
• Rigorous testing using molecular evolution principles is crucial for understanding the biological role of genomic features.
• Future research should focus on developing robust methods to ascertain function for newly identified ncRNAs.