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Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

ABSTRACT: Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features.

SUBMITTER: Zhang J

PROVIDER: S-EPMC1462353 | biostudies-other | 2002 Dec

REPOSITORIES: biostudies-other

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Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

Zhang Jianzhi J Webb David M DM Podlaha Ondrej O

Genetics 20021201 4

Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely tar ...[more]

PMID: 12524352

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Project description:Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution, a mutant yeast strain was engineered to translate a codon ambiguously (mistranslation). It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. Genomic analysis demonstrated that adaptation was primarily mediated by large-scale chromosomal duplication and deletion events, suggesting that errors during protein synthesis promote the evolution of genome architecture. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome-mediated protein degradation and protein synthesis. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. However, there was a strong evolutionary trade-off between adaptation to mistranslation and survival upon starvation: the evolved lines showed fitness defects and impaired capacity to degrade mature ribosomes upon nutrient limitation. Moreover, as a response to an enhanced energy demand of accelerated protein turnover, the evolved lines exhibited increased glucose uptake by selective duplication of hexose transporter genes. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. Our work also indicates that translational fidelity and the ubiquitin-proteasome system are functionally linked to each other and may, therefore, co-evolve in nature.

Dataset Information

Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

Publications

Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

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