title: Subfunctionalization via adaptive evolution influenced by genomic context: the case of histone chaperones ASF1a and ASF1b.
abstract: Gene duplication is regarded as the main source of adaptive functional novelty in eukaryotes. Processes such as neo- and subfunctionalization impact the evolution of paralogous proteins where functional divergence is frequently key to retain the gene copies. Here, we examined antisilencing function 1 (ASF1), a conserved eukaryotic H3-H4 histone chaperone, involved in histone dynamics during replication, transcription, and DNA repair. Although yeast feature a single ASF1 protein, two paralogs exist in most vertebrates, termed ASF1a and ASF1b, with distinct cellular roles in mammals. To explain this division of tasks, we integrated evolutionary and comparative genomic analyses with biochemical and structural approaches. First, we show that a duplication event at the ancestor of jawed vertebrates, followed by ASF1a relocation into an intron of the minichromosome maintenance complex component 9 (MCM9) gene at the ancestor of tetrapods, provided a different genomic environment for each paralog with marked differences of GC content and DNA replication timing. Second, we found signatures of positive selection in the N- and C-terminal regions of ASF1a and ASF1b. Third, we demonstrate that regions outside the primary interaction surface are key for the preferential interactions of the human paralogs with distinct H3-H4 chaperones. On the basis of these data, we propose that ASF1 experienced subfunctionalization shaped by the adaptation of the genes to their respective genomic context, reflecting a case of genomic context-driven escape from adaptive conflict.
authors: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors: Federico
authors: F
authors: Abascal
authors: Armelle
authors: A
authors: Corpet
authors: Zachary A
authors: ZA
authors: Gurard-Levin
authors: David
authors: D
authors: Juan
authors: Françoise
authors: F
authors: Ochsenbein
authors: Daniel
authors: D
authors: Rico
authors: Alfonso
authors: A
authors: Valencia
authors: Geneviève
authors: G
authors: Almouzni
mesh_terms: D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D001499:Bayes Theorem; D019143:Evolution, Molecular; D020440:Gene Duplication; D005786:Gene Expression Regulation; D023281:Genomics; D056488:Histone Chaperones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D012641:Selection, Genetic; D016415:Sequence Alignment; D014714:Vertebrates
chemical_list: D056488:Histone Chaperones
keywords: ASF1; chromatin dynamics; evolution; histone chaperones; structure