Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

The data available for a number of the gene families suggest that they may not have simple single functions but instead pleiotropic effects. While it seems natural that most studies have focused on inferred specific functions, which are often related to possible disease mechanisms, we advocate for investigators to keep a broad picture in mind. For example, a number of studies have focused on possible brain expansion effects for DUF1220/Olduvai repeats in the lineage toward humans, but we show that such correlations can be drawn for all of the core duplicon gene families (Table 1) . Our own work with SPATA31 had initially focused on the repair of UV-induced DNA damage because of the newly acquired protein domains. However, the incidental observation that fibroblast cells with manipulated functional copy numbers of SPATA31 exhibited altered senescence led us to study a possible connection to aging. The most direct connections of core duplicon gene families lie in their involvement in causing chromosomal aberrations and microdeletions. But this could be due to their general repeat structure, which makes them prone to recombinational unequal cross-over mechanisms that would also affect other genes in the respective regions. Hence, the involvement in such diseases may not necessarily serve as a direct pointer toward their protein functions.