A novel domain suggests a ciliary function for ASPM, a brain size determining gene

Area of Science:

• Genetics
• Cell Biology
• Evolutionary Biology

Background:

• The abnormal spindle-like microcephaly-associated protein (ASPM) is implicated in neurogenesis and cerebral cortical size.
• ASPM's rapid evolution in hominids has been linked to its proposed role in mitosis.
• Prior research suggested ASPM mutations cause primary microcephaly.

Purpose of the Study:

• To identify novel protein domains within ASPM.
• To explore alternative functions of ASPM beyond neurogenesis.
• To investigate the evolutionary significance of ASPM.

Main Methods:

• Bioinformatic analysis to identify conserved protein domains.
• Comparative genomics to study ASPM evolution.
• Literature review of proteins containing homologous domains.

Main Results:

• ASPM's N-terminal domain belongs to a novel ASH (ASPM, SPD-2, Hydin) domain family.
• ASH domains are found in proteins associated with cilia, flagella, centrosomes, and the Golgi complex.
• Genes encoding ASH domains are candidates for primary ciliary dyskinesias.

Conclusions:

• The identification of the ASH domain suggests ASPM may function in sperm flagella or ependymal cell cilia.
• ASPM's rapid evolution might reflect selective pressures on ciliary function, not solely on mitosis.
• This finding broadens the potential roles of ASPM in human health and disease.