OpenLB Open Library of Bioscience

Molecular evolutionary analysis of human primary microcephaly genes.

Nashaiman Pervaiz, Hongen Kang, Yiming Bao, Amir Ali Abbasi
Author Information
  1. Nashaiman Pervaiz: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
  2. Hongen Kang: China National Center for Bioinformation and National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
  3. Yiming Bao: China National Center for Bioinformation and National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. baoym@big.ac.cn.
  4. Amir Ali Abbasi: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. abbasiam@qau.edu.pk. ORCID

Abstract

BACKGROUND: There has been a rapid increase in the brain size relative to body size during mammalian evolutionary history. In particular, the enlarged and globular brain is the most distinctive anatomical feature of modern humans that set us apart from other extinct and extant primate species. Genetic basis of large brain size in modern humans has largely remained enigmatic. Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. For instance, the brain size of microcephaly patients is similar to the brain size of Pan troglodyte and the very early hominids like the Sahelanthropus tchadensis and Australopithecus afarensis.
RESULTS: The present study investigates the molecular evolutionary history of subset of autosomal recessive primary microcephaly (MCPH) genes; CEP135, ZNF335, PHC1, SASS6, CDK6, MFSD2A, CIT, and KIF14 across 48 mammalian species. Codon based substitutions site analysis indicated that ZNF335, SASS6, CIT, and KIF14 have experienced positive selection in eutherian evolutionary history. Estimation of divergent selection pressure revealed that almost all of the MCPH genes analyzed in the present study have maintained their functions throughout the history of placental mammals. Contrary to our expectations, human-specific adoptive evolution was not detected for any of the MCPH genes analyzed in the present study.
CONCLUSION: Based on these data it can be inferred that protein-coding sequence of MCPH genes might not be the sole determinant of increase in relative brain size during primate evolutionary history.

Keywords

MeSH Term

Animals
Brain
Evolution, Molecular
Female
Humans
Microcephaly
Placenta
Pregnancy
Primates