Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Results Probl Cell Differ. 2020;69:199-223. doi: 10.1007/978-3-030-51849-3_7.
Many complex diseases are expressed with high incidence only in certain populations. Genealogy studies determine that these diseases are inherited with a high probability. However, genetic studies have been unable to identify the genomic signatures responsible for such heritability, as identifying the genetic variants that make a population prone to a given disease is not enough to explain its high occurrence within the population. This gap is known as the missing heritability problem. We know that the microbiota plays a very important role in determining many important phenotypic characteristics of its host, in particular the complex diseases for which the missing heritability occurs. Therefore, when computing the heritability of a phenotype, it is important to consider not only the genetic variation in the host but also in its microbiota. Here we test this hypothesis by studying an evolutionary model based on gene regulatory networks. Our results show that the holobiont (the host plus its microbiota) is capable of generating a much larger variability than the host alone, greatly reducing the missing heritability of the phenotype. This result strongly suggests that a considerably large part of the missing heritability can be attributed to the microbiome.
许多复杂疾病仅在特定人群中表现出高发病率。家谱研究确定这些疾病具有较高的遗传概率。然而，遗传研究无法确定导致这种遗传性的基因组特征，因为确定使人群易患特定疾病的遗传变异不足以解释其在人群中的高发生率。这种差距被称为遗传缺失问题。我们知道，微生物组在决定其宿主的许多重要表型特征方面起着非常重要的作用，特别是对于发生遗传缺失的复杂疾病。因此，在计算表型的遗传率时，不仅要考虑宿主的遗传变异，还要考虑其微生物组。在这里，我们通过研究基于基因调控网络的进化模型来检验这一假设。我们的结果表明，后生生物（宿主及其微生物组）能够产生比宿主本身更大的可变性，大大降低了表型的遗传缺失。这一结果强烈表明，相当大一部分遗传缺失可以归因于微生物组。
