Tandem repeat accumulation drives evolution in great apes

Tandem repeats (also known as mini-/microsatellites) used to be considered 'neutral' junk genome, yet they are proving themselves quite more than just that.

M. Farré et al. Assessing the Role of Tandem Repeats in Shaping the Genomic Architecture of Great Apes. PLoS ONE 2011. Open access.

Among other things, this paper is a great manual to better understanding the differences between great apes (including humans) chromosome by chromosome:

Chromosome 1.

Human chromosome 1 is considered to be the derived form, showing a pericentric inversion when compared to chimpanzee and orangutan chromosome 1. The human tandem repeat landscape also differs from the other two great apes (HSA vs PTR: p-value = 0.006; HSA vs PPY: p-value = 0.000).

Chromosome 2.

It is well known that human chromosome 2 derives from the ancestral form by a fusion of two hominoid homolog chromosomes [1]. The ancestral 2a form corresponds to HSA2pq and also has suffered a pericentric inversion in the human form, whereas the ancestral 2b form has not suffered further reorganizations. The tandem repeat contour is different between human and the other great apes regarding chromosome 2a form (HSA vs PTR: p-value = 0.000; HSA vs PPY: p-value = 0.000) but is maintained in the homologous chromosome 2b form (HSA vs PTR: p-value = 0.738; HSA vs PPY: p-value = 0.192).

Chromosome 3.

Human and chimpanzee chromosomes are the derived forms, with an inverted region compared to orangutan chromosome. The tandem repeats distribution confirms this pattern (HSA vs PTR: p-value = 0.062; HSA vs PPY: p-value = 0.009).

Chromosome 4.

All the great apes have a derivative chromosome 4 that evolved differently since their common ancestor. We found a different tandem repeats distribution between human and chimpanzee forms but the same distribution between human and orangutan forms (HSA vs PTR: p-value = 0.022; HSA vs PPY: p-value = 0.272).

Chromosome 5.

Human chromosome is considered the ancestral form, whereas the chimpanzee and the orangutan have derived forms due to pericentric inversions. The tandem repeats landscape is consistent with this pattern (HSA vs PTR: p-value = 0.031; HSA vs PPY: p-value = 0.001).

Chromosome 6.

The three species shared the same chromosome form, which is considered to be ancestral. We found the same tandem repeat profile between human and chimpanzee (HSA vs PTR: p-value = 0.069) but it differs between human and orangutan (HSA vs PPY: p-value = 0.003).

Chromosome 7.

The orangutan chromosome represents the ancestral form, while human and chimpanzee share a pericentric inversion. We found the same tandem repeats pattern in human and chimpanzee (HSA vs PTR: p-value = 0.203) but this was different in orangutan (HSA vs PPY: p-value = 0.050) (Fig. 4a).

Chromosome 8.

The three hominoid species share the same form but we detected an insertion of ~3Mb in the orangutan chromosome 8 (Table 2). This difference is reflected in the tandem repeats landscape, being equal between human and chimpanzee (p-value = 0.128) but different in orangutan (p-value = 0.009) (Fig. 4b).

Chromosome 9.

All three species have different chromosomal forms, being the orangutan chromosome the ancestral one. Tandem repeats distribution is consistent with these differences (HSA vs PTR: p-value = 0.002; HSA vs PPY: p-value = 0.000).

Chromosome 10.

Orangutan chromosome 10 is considered to be the ancestral form, which differs from human and chimpanzee forms by a paracentric inversion. We found that human and orangutan have a different tandem repeat pattern (p-value = 0.001) as well as human and chimpanzee (p-value = 0.010), although the same pattern between these two species was expected.

Chromosome 11.

The ancestral chromosome form is conserved in orangutan, which differs from the human chromosome by a pericentric inversion and from chimpanzee by a pericentric inversion and an insertion of ~400 Kb (Table 2). These differences are also reflected in the tandem repeat distribution (HSA vs PTR: p-value = 0.016; HSA vs PPY: p-value = 0.000).

Chromosome 12.

Human and orangutan share the same form, which is considered the ancestral. Chimpanzee differs from them by a pericentric inversion. In this case, the tandem repeats landscape is different between human and chimpanzee (p-value = 0.050) and between human and orangutan (p-value = 0.004).

Chromosome 13.

Human and chimpanzee share the same form and have the same tandem repeats pattern (p-value = 0.072), while orangutan have a ~100Kb insertion (Table 2) and shows a different tandem repeats pattern (p-value = 0.003).

Chromosome 14.

All great apes share the same chromosome form and also the same tandem repeats landscape (HSA vs PTR: p-value = 0.051; HSA vs PPY: p-value = 0.051).

Chromosome 15.

All great apes have different chromosome forms and different tandem repeats profile (HSA vs PTR: p-value = 0.004; HSA vs PPY: p-value = 0.001).

Chromosome 16.

All great apes have different chromosome forms and different tandem repeats profile (HSA vs PTR: p-value = 0.001; HSA vs PPY: p-value = 0.000).

Chromosome 17.

Human and orangutan share the same ancestral form, while chimpanzee suffered a pericentric inversion. This pattern is in agreement with the tandem repeats distribution (HSA vs PTR: p-value = 0.030; HSA vs PPY: p-value = 0.106).

Chromosome 18.

Chimpanzee and orangutan share a chromosome form ancestral to great apes, which differs from the human by a pericentric inversion. This is not observed in the tandem repeats profile, given that all the species share the same distribution (HSA vs PTR: p-value = 0.095; HSA vs PPY: p-value = 0.206).

Chromosome 19, 20, 21 and 22.

All great apes share the same chromosome form and also the same tandem repeats landscape [HSA19 (PTR: p-value = 0.127; PPY: p-value = 0.161) HSA20 (PTR: p-value = 0.138; PPY: p-value = 0.051) HSA21 (PTR: p-value = 0.106; PPY: p-value = 0.111) HSA22 (PTR: p-value = 0.082; PPY: p-value = 0.051)].

Chromosome X.

Human and chimpanzee share the same ancestral form while orangutan has a ~2Mb insertion (Table 2). Tandem repeat pattern is in agreement with human-orangutan evolution (p-value = 0.021) but not with human-chimpanzee history (p-value = 0.000).

But while this is most interesting, it is not the only or main finding of this paper: the authors find that tandem repeats accumulate in the evolutionary breakpoint regions (EBRs) at higher rate than expected under neutrality conditions. Instead the homologous synteny blocks (HSB), highly conserved areas, display lower rate of tandem repeats than expected. 

Although no specific repeat motif was exclusively present in EBRs or HSBs, 17 different microsatellites motifs were significantly accumulated in EBRs. Notably, out of these overrepresented tandem repeats, the AAAT was the most frequently detected. It has been described that this motif could form single-stranded coils [24], favoring chromatin instability and increasing the likelihood to break.