Evolutionary origins of a bioactive peptide buried within preproalbumin

The de novo evolution of proteins is now considered a frequented route for biological innovation, but the genetic and biochemical processes that lead to each newly created protein are often poorly documented. The common sunflower (Helianthus annuus) contains the unusual gene PawS1 (Preproalbumin with SFTI-1) that encodes a precursor for seed storage albumin; however, in a region usually discarded during albumin maturation, its sequence is matured into SFTI-1, a protease-inhibiting cyclic peptide with a motif homologous to unrelated inhibitors from legumes, cereals, and frogs. To understand how PawS1 acquired this additional peptide with novel biochemical functionality, we cloned PawS1 genes and showed that this dual destiny is over 18 million years old. This new family of mostly backbone-cyclic peptides is structurally diverse, but the protease-inhibitory motif was restricted to peptides from sunflower and close relatives from its subtribe. We describe a widely distributed, potential ev...蛋白质从头演化（de novo evolution）现已被公认为驱动生物创新的常见路径，但介导新生蛋白质产生的遗传与生化过程往往鲜有详实记载。普通向日葵（Helianthus annuus）携带有特殊基因PawS1（Preproalbumin with SFTI-1，即携带SFTI-1的前原白蛋白），该基因编码一种种子储存白蛋白前体；而在白蛋白成熟过程中通常被切除丢弃的区域内，其序列可被加工为SFTI-1——一种蛋白酶抑制性环肽（protease-inhibiting cyclic peptide），其基序（motif）与豆科植物、谷类作物及蛙类来源的无关抑制剂具有同源性。为解析PawS1如何获得这一具备全新生化功能的额外肽段，我们克隆了PawS1基因，并证实这种"双重命运"的演化历史已超过1800万年。该家族的肽类大多为骨架环化结构，具有丰富的结构多样性，但蛋白酶抑制基序仅存在于向日葵及其所属亚族的近缘物种的肽段中。我们对一类广泛分布的潜在演化...