Figure 1.
The sarcomere “C-zone” is home to the MyBP-C/H family of regulatory proteins. (A) A schematic of the vertebrate skeletal muscle sarcomere, consisting of interdigitating myosin thick- and actin thin-filaments showing the “C-zone” (black) and expanded view of half-thick filament illustrating a mixture of MyBP-C/H molecules within the C-zone with their N- and C-termini identified. (B) Domain structure and homology among MyBP-C and MyBP-H isoforms showing conservation of C-terminal, myosin thick filament anchoring domains. (C) Normalized abundance of individual myosin heavy chain isoforms (with gene names in parentheses) in embryonic hindlimb buds (n = 3 replicates of 6–10 pooled limb buds each) and prenatal and adult rat tibialis anterior (TA) muscle samples (n = 3 per timepoint) relative to total myosin heavy chain abundance at each timepoint. (D) Abundance of individual myosin binding protein (MyBP) isoforms in embryonic hindlimb bud (none detected) and prenatal and adult rat TA muscle samples, relative to total muscle myosin heavy chain. Data are presented as means ± 1 SD. (E) A midpoint-rooted Maximum Likelihood consensus tree of the MyBP family based on an alignment of three C-terminal globular domains (294 amino acids) conserved among all family members from four species. The percentage of trees, from 100 bootstrapped replicates, in which the associated sequences clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the JTT model and then selecting the topology with superior log likelihood value. The tree is drawn to scale with branch lengths equal to the number of substitutions per site. Sequences cluster into four distinct clades, corresponding to the four paralogous MyBP gene family members. Orthologous sequences from each species are represented within each clade, indicating divergence and specialization early in vertebrate evolution. The grouping of mammalian MyBP-H and MyBP-HL, as well as zebrafish fMyBP-C (a/b) and MyBP-H (a/b) is indicative of more recent, lineage-specific gene duplication events (nodes with black dots).

The sarcomere “C-zone” is home to the MyBP-C/H family of regulatory proteins. (A) A schematic of the vertebrate skeletal muscle sarcomere, consisting of interdigitating myosin thick- and actin thin-filaments showing the “C-zone” (black) and expanded view of half-thick filament illustrating a mixture of MyBP-C/H molecules within the C-zone with their N- and C-termini identified. (B) Domain structure and homology among MyBP-C and MyBP-H isoforms showing conservation of C-terminal, myosin thick filament anchoring domains. (C) Normalized abundance of individual myosin heavy chain isoforms (with gene names in parentheses) in embryonic hindlimb buds (n = 3 replicates of 6–10 pooled limb buds each) and prenatal and adult rat tibialis anterior (TA) muscle samples (n = 3 per timepoint) relative to total myosin heavy chain abundance at each timepoint. (D) Abundance of individual myosin binding protein (MyBP) isoforms in embryonic hindlimb bud (none detected) and prenatal and adult rat TA muscle samples, relative to total muscle myosin heavy chain. Data are presented as means ± 1 SD. (E) A midpoint-rooted Maximum Likelihood consensus tree of the MyBP family based on an alignment of three C-terminal globular domains (294 amino acids) conserved among all family members from four species. The percentage of trees, from 100 bootstrapped replicates, in which the associated sequences clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the JTT model and then selecting the topology with superior log likelihood value. The tree is drawn to scale with branch lengths equal to the number of substitutions per site. Sequences cluster into four distinct clades, corresponding to the four paralogous MyBP gene family members. Orthologous sequences from each species are represented within each clade, indicating divergence and specialization early in vertebrate evolution. The grouping of mammalian MyBP-H and MyBP-HL, as well as zebrafish fMyBP-C (a/b) and MyBP-H (a/b) is indicative of more recent, lineage-specific gene duplication events (nodes with black dots).

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