Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
Genome Res. 2010 Jul;20(7):929-37. doi: 10.1101/gr.102160.109. Epub 2010 May 20.
Gene expression becomes more variable with age, and it is widely assumed that this is due to a decrease in expression regulation. But currently there is no understanding how gene expression regulatory patterns progress with age. Here we explored genome-wide gene expression variation and regulatory loci (eQTL) in a population of developing and aging C. elegans recombinant inbred worms. We found almost 900 genes with an eQTL, of which almost half were found to have a genotype-by-age effect ((gxa)eQTL). The total number of eQTL decreased with age, whereas the variation in expression increased. In developing worms, the number of genes with increased expression variation (1282) was similar to the ones with decreased expression variation (1328). In aging worms, the number of genes with increased variation (1772) was nearly five times higher than the number of genes with a decreased expression variation (373). The number of cis-acting eQTL in juveniles decreased by almost 50% in old worms, whereas the number of trans-acting loci decreased by approximately 27%, indicating that cis-regulation becomes relatively less frequent than trans-regulation in aging worms. Of the 373 genes with decreased expression level variation in aging worms, approximately 39% had an eQTL compared with approximately 14% in developing worms. (gxa)eQTL were found for approximately 21% of these genes in aging worms compared with only approximately 6% in developing worms. We highlight three examples of linkages: in young worms (pgp-6), in old worms (daf-16), and throughout life (lips-16). Our findings demonstrate that eQTL patterns are strongly affected by age, and suggest that gene network integrity declines with age.
基因表达随年龄的增长而变得更加多变，人们普遍认为这是由于表达调控的下降所致。但目前还不清楚基因表达调控模式是如何随年龄变化的。在这里，我们研究了一个发育中和衰老的 C. elegans 重组近交系蠕虫群体的全基因组基因表达变异和调控基因座 (eQTL)。我们发现了近 900 个具有 eQTL 的基因，其中近一半被发现具有基因型与年龄的效应 (gxa)eQTL。随着年龄的增长，eQTL 的总数减少，而表达的变化增加。在发育中的蠕虫中，表达变化增加的基因数量 (1282) 与表达变化减少的基因数量 (1328) 相似。在衰老的蠕虫中，表达变化增加的基因数量 (1772) 几乎是表达变化减少的基因数量 (373) 的五倍。在老年蠕虫中，青少年时期的顺式作用 eQTL 数量减少了近 50%，而反式作用基因座数量减少了约 27%，这表明在衰老的蠕虫中，顺式调控比反式调控相对不那么频繁。在衰老的蠕虫中，表达水平变化减少的 373 个基因中，约有 39%有 eQTL，而在发育中的蠕虫中，约有 14%有 eQTL。在衰老的蠕虫中，大约有 21%的这些基因有 (gxa)eQTL，而在发育中的蠕虫中，只有大约 6%有 (gxa)eQTL。我们强调了三个例子的联系：在年轻的蠕虫中（pgp-6），在年老的蠕虫中（daf-16），以及在整个生命周期中（lips-16）。我们的发现表明，eQTL 模式受年龄的强烈影响，并表明随着年龄的增长，基因网络的完整性下降。
