Poster  D23SY17PS0425

Evolutionary history of the 17q21 human polymorphic inversion

Author(s): Alves JMF, Lopes A, Heutink P, Chikhi L, Amorim A

Summary:

With the aid of novel and powerful molecular biology techniques the study of the structural plasticity of the genome has gained momentum, and one particular subtype of chromosomal rearrangement – inversions – was recently found to be far more common than predicted from classical cytogenetics. Moreover, large inversions have been identified at high frequency in some human populations.

One particularly large inversion (900 kb) described in humans and several Great Apes, namely 17q21, has been shown to exhibit ‘frozen’ haplotypes (H1 and H2) which were originally identified by specific mutations and by their opposite orientations. The fact that they accumulate mutations independently is not necessarily surprising since recombination is expected to be limited between inverted regions. However, three surprising results were also found (i) age estimates of the inverted-associated haplotype (H2) are in the order of magnitude of millions of years, and (ii) the frequency of the inverted haplotypes vary between 5 and 35% in Europe only, (iii) cases were found in which the inversion status was in contradiction with the molecular haplotype, i.e. some H2 haplotypes (as defined by specific mutations) were in the same orientation as H1.

These results suggest that (i) the inversion might be recurrent despite its size, or (ii) the polymorphism was kept during a large evolutionary timescale and resisted various speciation processes since it is observed in other Apes.

In order to clarify the complex history of 17q21 human polymorphic inversion we are merging NGS data from 14 populations with cytogenetic (e.g. Fluorescent in situ hybridization) and molecular techniques. Furthermore, we will apply population genetics approaches to compare different evolutionary models.