The adaptive molecular landscape of reprogrammed telomeric sequences

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• Telomeric sequences are crucial for chromosome stability and vary across species.
• The co-evolution of telomeres and telomere-binding proteins is complex.
• Understanding adaptation to novel telomeric sequences is challenging in natural systems.

Purpose of the Study:

• To investigate the molecular and fitness consequences of engineering human-like telomeric repeats in yeast.
• To identify the adaptive mechanisms enabling yeast to evolve in response to reprogrammed telomeres.

Main Methods:

• Engineering yeast strains with human telomeric repeats.
• Analyzing genome instability and proteome changes post-engineering.
• Conducting adaptive evolution experiments.
• Identifying genetic mutations and chromosomal alterations conferring adaptation.

Main Results:

• Initial telomere sequence exchange led to genome instability, proteome remodeling, and reduced fitness.
• Adaptive evolution selected for recurrent mutations, including TBF1 gene amplification.
• Complex aneuploidies and attenuation of DNA damage response were observed.
• These adaptations facilitated survival and proliferation with humanized telomeres.

Conclusions:

• The study elucidates the adaptive molecular landscape for responding to reprogrammed telomeric sequences.
• Recurrent genetic and chromosomal changes drive adaptation to novel telomere structures.
• Yeast provides a model for studying telomere sequence evolution and adaptation mechanisms.