Life cycle of an n-globin pseudogene microsatellite locus

Microsatellites are composed of tandemly repeated short motifs of 1–6 nucleotides. They are common in eukaryotic genomes; in humans they make up as much as 3% of the genome (Lander et al., 2001). These repeat-containing loci tend to be hypervariable with variation occurring among individuals of the same species as well as between species. The origin and evolution of microsatellites remain a major puzzle. The birth of a tetranucleotide repeat (ATGT) in the lineage leading to African apes (gorilla, bonobo and chimpanzee) and humans was documented in the nglobin pseudogene (Messier et al., 1996). To test whether the locus is under further expansion or degeneration or if there are any variations as proposed in the lifecycle of the microsatellites (Buschiazzo and Gemmell, 2006), we analyzed positions chr11:5263801:5263831 (hg19) in 82 samples from the 1000 Genomes Project (Genomes Project et al., 2010). To obtain reliable read coverage for the locus, we selected Illumina exome sequencing data and visually inspected the INDEL length in the reads aligned to the locus. We found a repeat deletion (4 bases) of the 4-mer microsatellite locus in 46 samples (56%) relative to reference allele, as supported by at least two reads in each sample. We assume that the longer (reference) microsatellite allele is ancestral, as at least two mutations are reported in this allele (rs34312249 and rs147740082), suggesting a degeneration process of the pure microsatellite locus. The short allele had 28% frequency in analyzed samples. The genus Homo is believed to have evolved 2.0Myr (Curnoe, 2010) and modern humans 0.2Myr (Vigilant et al., 1991) ago. Last evolutionary change in the nglobin pseudogene locus is documented between chimpanzees and humans when the microsatellite locus was expanded in humans. Unfortunately, intraspecies variation in the locus is unknown in chimpanzees and gorillas and we were unable to find the locus in the Neanderthal genome, presumably due to its incompleteness (Green et al., 2006). The locus alteration from orangutan to gorilla took ∼7.0Myr followed by species evolution with no change in the locus (gorilla to chimpanzee). Similarly, the evolution of the chimpanzee to the genus Homo took ∼3.0Myr with an accompanying n-globin microsatellite locus expansion. As time required for subsequent stage of life cycle seems to decrease by