Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Tokyo, 153-8902, Japan.
Center for Complex Systems Research, Universal Biology Institute, University of Tokyo, Tokyo, Japan.
BMC Ecol Evol. 2021 Jun 6;21(1):110. doi: 10.1186/s12862-021-01841-6.
Mendelian inheritance is a fundamental law of genetics. When we consider two genomes in a diploid cell, a heterozygote's phenotype is dominated by a particular homozygote according to the law of dominance. Classical Mendelian dominance is concerned with which proteins are dominant, and is usually based on simple genotype-phenotype relationship in which one gene regulates one phenotype. However, in reality, some interactions between genes can exist, resulting in deviations from Mendelian dominance. Whether and how Mendelian dominance is generalized to the phenotypes of gene expression determined by gene regulatory networks (GRNs) remains elusive.
Here, by using the numerical evolution of diploid GRNs, we discuss whether the dominance of phenotype evolves beyond the classical Mendelian case of one-to-one genotype-phenotype relationship. We examine whether complex genotype-phenotype relationship can achieve Mendelian dominance at the expression level by a pair of haplotypes through the evolution of the GRN with interacting genes. This dominance is defined via a pair of haplotypes that differ from each other but have a common phenotype given by the expression of target genes. We numerically evolve the GRN model for a diploid case, in which two GRN matrices are added to give gene expression dynamics and simulate evolution with meiosis and recombination. Our results reveal that group Mendelian dominance evolves even under complex genotype-phenotype relationship. Calculating the degree of dominance shows that it increases through the evolution, correlating closely with the decrease in phenotypic fluctuations and the increase in robustness to initial noise. We also demonstrate that the dominance of gene expression patterns evolves concurrently. This evolution of group Mendelian dominance and pattern dominance is associated with phenotypic robustness against meiosis-induced genome mixing, whereas sexual recombination arising from the mixing of genomes from the parents further enhances dominance and robustness. Due to this dominance, the robustness to genetic differences increases, while optimal fitness is sustained to a significant difference between the two genomes.
Group Mendelian dominance and gene-expression pattern dominance are achieved associated with the increase in phenotypic robustness to noise.
孟德尔遗传是遗传学的基本定律。当我们考虑二倍体细胞中的两个基因组时，根据显性法则，杂合体的表型由特定的纯合体主导。经典的孟德尔显性是关于哪些蛋白质是显性的，并且通常基于一个基因调节一个表型的简单基因型-表型关系。然而，在现实中，基因之间可能存在一些相互作用，导致偏离孟德尔显性。孟德尔显性是否以及如何推广到由基因调控网络（GRN）决定的基因表达表型仍然难以捉摸。
在这里，我们通过使用二倍体 GRN 的数值演化，讨论了表型的显性是否超越了一个对一个基因型-表型关系的经典孟德尔情况。我们通过相互作用基因的 GRN 演化，检查了复杂的基因型-表型关系是否可以通过一对单倍型在表达水平上实现孟德尔显性，这种显性是通过一对彼此不同但具有由目标基因表达决定的共同表型的单倍型来定义的。我们对二倍体情况的 GRN 模型进行数值演化，其中两个 GRN 矩阵被添加以给出基因表达动力学，并模拟减数分裂和重组的演化。我们的结果表明，即使在复杂的基因型-表型关系下，群体孟德尔显性也会进化。通过计算显性程度，我们发现它随着演化而增加，与表型波动的减少和对初始噪声的稳健性的增加密切相关。我们还证明了基因表达模式的显性也会同时进化。这种群体孟德尔显性和模式显性的进化与表型对减数分裂诱导的基因组混合的稳健性有关，而来自父母的基因组混合产生的性重组进一步增强了显性和稳健性。由于这种显性，对遗传差异的稳健性增加，而最佳适应性则在两个基因组之间的显著差异下得以维持。
群体孟德尔显性和基因表达模式显性与表型对噪声的稳健性增加相关。
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