Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes

Abstract

Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ∼100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.

Novel H3K4me3 marks are enriched at human- and chimpanzee-specific cytogenetic structures

“…CNTN4 and CHL1 are within the subtelomeric region of the HSA3 short arm. The DPP10 locus (2q14.1) maps only 1 Mbp away from the above-mentioned fusion point of HSA2 (IJdo et al 1991;Fan et al 2002; The Chimpanzee Sequencing and Analysis Consortium Figure 1. Karyotype-wide mapping of the regions with human-specific enrichment (n = 410, blue) and depletion (n = 61, green) of H3K4me3 modifications in prefrontal neurons.…”

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

“…Here we present our analysis of the sequence of human chromosomes 2 and 4. For chromosome 2, we analyse the region containing the ancestral chromosome fusion event 2 and describe possible mechanisms for the inactivation of the vestigial centromere. For chromosome 4, we discover some regions with the lowest and highest (GþC) content in the human genome, as well as the putative largest 'gene deserts' .…”

Selective POTE Paralogs on Chromosome 2 are Expressed in Human Embryonic Stem Cells

“…The pericentromeric regions generally exhibit low transcriptional activity [11]. During human evolution, two ancestral ape chromosomes were fused into one to generate the present human chromosome 2 [12,13]. One of the two ancestral centromeres was located at 2q21.2, and the POTE gene cluster at 2q21.1 is located in the pericentromeric region of this ancient centromere (Fig.…”