Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and...

Area of Science:

• Evolutionary biology
• Molecular evolution
• Genetics

Background:

• Adaptive genetic variation arises from de novo mutations, standing variation, and introgressive hybridization.
• Understanding how these sources influence phenotypic adaptation is crucial.
• Hemoglobin (Hb) adaptations in high-altitude mammals are key to hypoxia tolerance.

Purpose of the Study:

• To investigate the phenotypic effects of introgressed Hb mutations in Tibetan mastiffs.
• To trace the evolutionary origin of these adaptive Hb mutations.
• To compare molecular mechanisms of adaptation via introgression versus de novo mutation.

Main Methods:

• Protein engineering approach to study Tibetan wolf Hb mutations introgressed into Tibetan mastiffs.
• Site-directed mutagenesis to identify critical amino acid replacements.
• Analysis of gene conversion and introgression as mechanisms of genetic transfer.

Main Results:

• Introgressed Hb variants increase Hb-O2 affinity and enhance the Bohr effect.
• Affinity-enhancing mutations in Tibetan wolf originated from a β-globin pseudogene via interparalog gene conversion.
• A specific two-site amino acid replacement combination is required for increased Hb-O2 affinity.

Conclusions:

• Adaptive Hb mutations in Tibetan mastiffs were acquired through intragenomic and interspecific lateral gene transfer.
• The molecular basis of Hb adaptation in Tibetan mastiffs differs from adaptation via sequential de novo mutations.
• Introgression from distinct genetic sources provides unique pathways for rapid adaptation.