Conservation of a Chromosome 8 Inversion and Exon Mutations Confirm Common Gulonolactone Oxidase Gene Evolution Among...

Area of Science:

• Evolutionary biology
• Genomics
• Biochemistry

Background:

• Ascorbic acid (vitamin C) is essential for human health, acting as an antioxidant and facilitating collagen synthesis and iron absorption.
• Unlike most animals with a functional gulonolactone oxidase (GULO) gene, humans possess a non-functional GULO pseudogene (GULOP), necessitating dietary intake of vitamin C.
• Understanding the evolutionary history of GULO/GULOP is crucial for insights into vitamin C metabolism and gene evolution.

Purpose of the Study:

• To investigate the evolutionary conservation and mutation patterns of GULO and GULOP sequences across primate suborders (Haplorhini and Strepsirrhini).
• To compare GULO/GULOP evolution in primates with that of other placental mammals, including the Brazilian guinea pig and pika.
• To analyze the genomic context and synteny around the GULO/GULOP locus to identify conserved or variable rearrangements.

Main Methods:

• Phylogenetic analysis of GULOP exon sequences in Haplorhini and comparison with GULO sequences in Strepsirrhini.
• Sequence analysis of GULO and GULOP in placental mammals, including identification of potential functional or pseudogene sequences.
• Shared synteny analysis and Mauve alignment to examine gene order conservation and rearrangements around the GULO/GULOP locus.

Main Results:

• Conserved GULOP exons in Haplorhini primates showed high mutation rates post-divergence, which later decreased.
• Conserved indels were observed in Haplorhini GULOP sequences.
• An in-frame GULO sequence was found in the Brazilian guinea pig, and a potential GULOP in the pika, both exhibiting high substitution rates similar to Haplorhini primates.
• A conserved inversion around the GULO/GULOP locus was identified between Haplorhini and Strepsirrhini, though not directly associated with GULOP function.
• Variable inversion lengths and frequent rearrangements near GULOP involving KIF13B and MSRA genes were detected.

Conclusions:

• The GULOP gene in Haplorhini primates has undergone significant evolutionary changes, including high mutation rates and conserved rearrangements.
• The findings suggest a potential link between deleterious mutations in coding sequences and rapid substitution rates as an evolutionary response.
• Comparative genomics of GULO/GULOP across species provides insights into the evolution of vitamin C synthesis pathways and gene regulation.