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

Abstract

Illuminating the role of specific gene duplications within the human lineage can provide insights into human-specific adaptations. The so-called human core duplicon gene families have received particular attention in this respect, due to special features, such as expansion along single chromosomes, newly acquired protein domains and signatures of positive selection. Here, we summarize the data available for 10 such families and include some new analyses. A picture emerges that suggests broad functions for these protein families, possibly through modification of core cellular pathways. Still, more dedicated studies are required to elucidate the function of core-duplicons gene families and how they have shaped adaptations and evolution of humans.

Intrinsic Disorder in Human Proteins Encoded by Core Duplicon Gene Families

“…10−13 (iii) Almost all of these genes show ubiquitous or at least broad patterns of expression, while their ancestral progenitor genes often exhibit tissue-specific expression, mostly in the testis. 5 " The important conclusion of this study was that proteins encoded by these core duplicon gene families are multifunctional, with each potentially playing a number of important roles in various biological processes, 9 raising an important question on the molecular basis of such multifunctionality.…”

“…Approximately 30% of human core duplicon gene families show strong signs of positive selection. 8,9 It is assumed that human core duplicon gene families play an important role in the variability of the human genome. As duplicons "extras"they are more susceptible to mutations and with that to contributions to evolutionary developments.…”

“…Proteins encoded by core duplicon families are mainly involved in neuronal activities, signal transduction, cell proliferation, and muscle contraction. 9 In spite of their intriguing history and characteristics, core duplicons have not yet been studied extensively. Given the complexities of mapping repetitive regions against a reference genome, their study is very challenging.…”

“…Recently, some functional data available for 10 core duplicon gene families were summarized in a comprehensive study. 9 These 10 families (NBPF, RGPD, GUSBP, PMS2P, SPATA31, TRIM51, GOLGA8, NPIP, TBC1D3, and LRRC37) were selected based on the following criteria: 9 "(i) Their duplicates are generally confined to a single chromosome, partly in tandem but also dispersed along the chromosome. (ii) They have variable copy numbers in human populations and include some of the most variable human CNV genes (e.g., SPATA31, Morpheus (NPIP), and LRRC37A).…”

“…They have developed distinct features, such as, as aforementioned, the propensity to extend along single chromosomes and the ability to acquire new protein domains and with that new functions. Approximately 30% of human core duplicon gene families show strong signs of positive selection. , It is assumed that human core duplicon gene families play an important role in the variability of the human genome. As duplicons“extras”they are more susceptible to mutations and with that to contributions to evolutionary developments.…”