小柯机器人

近日，英国剑桥大学Caroline J. Watson和Jamie R. Blundell合作揭示血液中镶嵌染色体改变的突变率和适应性后果。相关论文于2023年9月11日在线发表于国际学术期刊《自然—遗传学》。

利用英国生物库（UK Biobank）约50万名参与者血液中的镶嵌染色体改变（mCA）克隆大小估计值，研究人员估算了获得性杂合增益、丢失和拷贝中性丢失事件的突变率和适应性后果。大多数杂合性突变具有中度到高度的健康影响，但发生率较低，比同等适合的单核苷酸变异少十倍以上。值得注意的例外是X和Y的镶嵌缺失，研究人员估计其突变率比常染色体mCA高出大约1000倍。

虽然大多数mCA随年龄增长而增加的方式与恒定增长率一致，但有些mCA表现出不同的行为，这表明它们的适应性可能取决于遗传变异、外在因素或适应性效应的分布。

据介绍，mCA在癌症中很常见，可能在诊断前几十年就出现了。定量地了解这些事件的发生率及其功能性后果，可以改善癌症风险预测和我们对体细胞进化的理解。

附：英文原文

Title: Mutation rates and fitness consequences of mosaic chromosomal alterations in blood

Author: Watson, Caroline J., Blundell, Jamie R.

Issue&Volume: 2023-09-11

Abstract: Mosaic chromosomal alterations (mCAs) are common in cancers and can arise decades before diagnosis. A quantitative understanding of the rate at which these events occur, and their functional consequences, could improve cancer risk prediction and our understanding of somatic evolution. Using mCA clone size estimates from the blood of approximately 500,000 UK Biobank participants, we estimate mutation rates and fitness consequences of acquired gain, loss and copy-neutral loss of heterozygosity events. Most mCAs have moderate to high fitness effects but occur at a low rate, being more than tenfold less common than equivalently fit single-nucleotide variants. Notable exceptions are mosaic loss of X and Y, which we estimate have roughly 1,000-fold higher mutation rates than autosomal mCAs. Although the way in which most mCAs increase in prevalence with age is consistent with constant growth rates, some mCAs exhibit different behavior, suggesting that their fitness may depend on inherited variants, extrinsic factors or distributions of fitness effects. A survey of the fitness effects conferred by mosaic chromosomal alterations (mCAs) in UK Biobank shows that most mCAs—despite being relatively infrequent—are associated with increased fitness. Mosaic loss of the sex chromosomes was more common but these events afforded only small fitness gains.

DOI: 10.1038/s41588-023-01490-z

Source: https://www.nature.com/articles/s41588-023-01490-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex