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Polymorphism, shared functions and convergent evolution of genes with sequences coding for polyalanine domains.
Hugo Lavoie1, Francois Debeane, Quoc-Dien Trinh
1Laboratoire de Neurogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.
Human Molecular Genetics
|October 2, 2003
Summary
Polyalanine expansions in proteins are linked to hereditary diseases. This study reveals these sequences are often polymorphic, suggesting a role in disease and convergent evolution.
Area of Science:
- Genomics
- Molecular Biology
- Human Genetics
Background:
- Expansions of polyalanine domains are implicated in nine hereditary diseases.
- Polymorphism in GC-rich sequences coding for polyalanine domains has been observed in humans.
Purpose of the Study:
- To identify all human genome sequences coding for polyalanine stretches longer than four alanines.
- To establish the degree of polymorphism in these sequences.
Main Methods:
- Bioinformatic identification of polyalanine-coding sequences in the human genome.
- Analysis of sequence length, repeat content (GCG/GCC), and polymorphism.
- Phylogenetic analysis of conserved protein families across species.
Main Results:
- Identified 494 human proteins with 604 polyalanine domains.
- 32% of sequences coding for >7 alanines were polymorphic.
- GCG codons are over-represented; sequence length and GCG/GCC content predict polymorphism.
- Polyalanine proteins primarily involved in transcriptional regulation across species.
- Polyalanine domains arose independently via convergent evolution in HOX, GATA, and EVX families.
- Domains are conserved in mammals but rarer/shorter in birds and fish.
Conclusions:
- Polymorphic polyalanine-coding sequences are strong candidates for mutations causing hereditary diseases.
- Convergent evolution likely contributed to the appearance of polyalanine domains in diverse protein families.