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Biomedical subjects

Yin-Qiu Wang

Publications and source records attributed to Yin-Qiu Wang.

3 recordsLinked to original sources

Adaptive evolution of primate TRIM5alpha, a gene restricting HIV-1 infection.

Recent studies showed that nonhuman primate TRIM5alpha can efficiently block HIV-1 infection in human cell lines. It can also restrict other retroviruses, therefore, suggested as a general defender against retrovirus infection. Here, we present an evolutionary analysis of TRIM5alpha in primates. Our results demonstrated that TRIM5alpha has been evolving rapidly in primates, which is likely caused by Darwinian positive selection. The SPRY domain of TRIM5alpha, which may be responsible for recognition of incoming viral capsids showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5alpha in primates might be an innate strategy developed in defending retrovirus infection during primate evolution. In addition, the comparative protein sequence analysis suggested that the amino acid substitution pattern at a single site (344R/Q/P) located in the SPRY domain may explain the differences in susceptibilities of HIV-1 infection in diverse primate species.

Adaptation, Biological↗

Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition.

Amino Acid Motifs↗

Molecular evolution of microcephalin, a gene determining human brain size.

Microcephalin gene is one of the major players in regulating human brain development. It was reported that truncated mutations in this gene can cause primary microcephaly in humans with a brain size comparable with that of early hominids. We studied the molecular evolution of microcephalin by sequencing the coding region of microcephalin gene in humans and 12 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results showed that microcephalin is highly polymorphic in human populations. We observed 22 substitutions in the coding region of microcephalin gene in human populations, with 15 of them causing amino acid changes. The neutrality tests and phylogenetic analysis indicated that the rich sequence variations of microcephalin in humans are likely caused by the combination of recent population expansion and Darwinian positive selection. The synonymous/non-synonymous analyses in primates revealed positive selection on microcephalin during the origin of the last common ancestor of humans and great apes, which coincides with the drastic brain enlargement from lesser apes to great apes. The codon-based neutrality test also indicated the signal of positive selection on five individual amino acid sites of microcephalin, which may contribute to brain enlargement during primate evolution and human origin.

Amino Acid Sequence↗