Molecular evolutionary analysis of human primary microcephaly genes

Area of Science:

• Evolutionary biology
• Genetics
• Neuroscience

Background:

• Mammalian evolution features a significant increase in brain size relative to body size.
• Enlarged, globular brains distinguish humans from other primates.
• Genes causing primary microcephaly (MCPH) are candidates for understanding human brain enlargement.

Purpose of the Study:

• Investigate the molecular evolutionary history of specific primary microcephaly (MCPH) genes.
• Analyze these genes across 48 mammalian species to understand brain size evolution.
• Identify potential genetic drivers of increased brain size in human evolution.

Main Methods:

• Analyzed a subset of autosomal recessive primary microcephaly (MCPH) genes: CEP135, ZNF335, PHC1, SASS6, CDK6, MFSD2A, CIT, and KIF14.
• Utilized codon-based substitution site analysis to detect positive selection.
• Estimated divergent selection pressure across mammalian evolutionary history.

Main Results:

• Positive selection was detected in ZNF335, SASS6, CIT, and KIF14 genes during eutherian evolution.
• Most analyzed MCPH genes maintained their functions throughout placental mammal history.
• No human-specific adaptive evolution was found in the studied MCPH genes.

Conclusions:

• Protein-coding sequences of MCPH genes may not solely explain the increase in relative brain size during primate evolution.
• Further research is needed to identify other genetic or regulatory factors contributing to human brain expansion.
• The evolutionary trajectory of brain size is likely influenced by a complex interplay of genetic elements.