Jakobson Christopher M, Hartl Johannes, Trébulle Pauline, Mülleder Michael, Jarosz Daniel F, Ralser Markus
Depasssrtment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
bioRxiv. 2024 Oct 22:2024.10.18.619054. doi: 10.1101/2024.10.18.619054.
Despite abundant genomic and phenotypic data across individuals and environments, the functional impact of most mutations on phenotype remains unclear. Here, we bridge this gap by linking genome to proteome in 800 meiotic progeny from an intercross between two closely related isolates adapted to distinct niches. Modest genetic distance between the parents generated remarkable proteomic diversity that was amplified in the progeny and captured by 6,476 genotype-protein associations, over 1,600 of which we resolved to single variants. Proteomic adaptation emerged through the combined action of numerous - and -regulatory mutations, a regulatory architecture that was conserved across the species. Notably, -regulatory variants often arose in proteins not traditionally associated with gene regulation, such as enzymes. Moreover, the proteomic consequences of mutations predicted fitness under various stresses. Our study demonstrates that the collective action of natural genetic variants drives dramatic proteome diversification, with molecular consequences that forecast phenotypic outcomes.
尽管有大量关于个体和环境的基因组及表型数据，但大多数突变对表型的功能影响仍不明确。在此，我们通过将来自适应不同生态位的两个密切相关分离株杂交产生的800个减数分裂后代的基因组与蛋白质组相联系，填补了这一空白。亲本之间适度的遗传距离产生了显著的蛋白质组多样性，这种多样性在后代中得到放大，并通过6476个基因型-蛋白质关联得以体现，其中超过1600个关联可解析为单个变异。蛋白质组适应性是通过众多调控突变的共同作用而出现的，这种调控结构在物种间是保守的。值得注意的是，调控变异常常出现在传统上与基因调控无关的蛋白质中，如酶。此外，突变的蛋白质组学后果预测了各种压力下的适应性。我们的研究表明，自然遗传变异的共同作用驱动了显著的蛋白质组多样化，其分子后果预示着表型结果。
