Late-replicating CNVs as a source of new genes

TL;DR

This study reveals that late-replicating CNV regions are hotspots for recent gene duplications, influencing genome evolution by generating new protein-coding genes in primates and mice.

Contribution

It demonstrates a link between DNA replication timing and the emergence of new genes through recent duplications in late-replicating regions.

Findings

Genes duplicated during primate evolution are enriched in late-replicating CNV regions.

Younger duplicated genes are more common in late-replicating regions.

The frequency of duplicates in late regions decreases with evolutionary age.

Abstract

Asynchronous replication of the genome has been associated with different rates of point mutation and copy number variation (CNV) in human populations. Here, we explored if the bias in the generation of CNV that is associated to DNA replication timing might have conditioned the birth of new protein-coding genes during evolution. We show that genes that were duplicated during primate evolution are more commonly found among the human genes located in late-replicating CNV regions. We traced the relationship between replication timing and the evolutionary age of duplicated genes. Strikingly, we found that there is a significant enrichment of evolutionary younger duplicates in late replicating regions of the human and mouse genome. Indeed, the presence of duplicates in late replicating regions gradually decreases as the evolutionary time since duplication extends. Our results suggest that the accumulation of recent duplications in late replicating CNV regions is an active process influencing genome evolution.