Research Paper Volume 10, Issue 4 pp 674—688
Involvement of SPATA31 copy number variable genes in human lifespan
- 1 Max-Planck Institute for Evolutionary Biology, 24306 Plön, Germany
- 2 Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany
received: March 6, 2018 ; accepted: April 14, 2018 ; published: April 19, 2018 ;https://doi.org/10.18632/aging.101421
How to Cite
Copyright: Bekpen et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The SPATA31 (alias FAM75A) gene family belongs to the core duplicon families that are thought to have contributed significantly to hominoid evolution. It is also among the gene families with the strongest signal of positive selection in hominoids. It has acquired new protein domains in the primate lineage and a previous study has suggested that the gene family has expanded its function into UV response and DNA repair. Here we show that over-expression of SPATA31A1 in fibroblast cells leads to premature senescence due to interference with aging-related transcription pathways. We show that there are considerable copy number differences for this gene family in human populations and we ask whether this could influence mutation rates and longevity in humans. We find no evidence for an influence on germline mutation rates, but an analysis of long-lived individuals (> 96 years) shows that they carry significantly fewer SPATA31 copies in their genomes than younger individuals in a control group. We propose that the evolution of SPATA31 copy number is an example for antagonistic pleiotropy by providing a fitness benefit during the reproductive phase of life, but negatively influencing the overall life span.