Novel crossover and recombination hotspots massively spread across primate genomes.

BACKGROUND: The recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination. METHODS: On a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse. RESULTS: We found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human. CONCLUSIONS: We report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned.

Tandem repeats ubiquitously flank and contribute to translation initiation sites.

BACKGROUND: While the evolutionary divergence of cis-regulatory sequences impacts translation initiation sites (TISs), the implication of tandem repeats (TRs) in TIS selection remains largely elusive. Here, we employed the TIS homology concept to study a possible link between TRs of all core lengths and repeats with TISs. METHODS: Human, as reference sequence, and 83 other species were selected, and data was extracted on the entire protein-coding genes (n = 1,611,368) and transcripts (n = 2,730,515) annotated for those species from Ensembl 102. Following TIS identification, two different weighing vectors were employed to assign TIS homology, and the co-occurrence pattern of TISs with the upstream flanking TRs was studied in the selected species. The results were assessed in 10-fold cross-validation. RESULTS: On average, every TIS was flanked by 1.19 TRs of various categories within its 120 bp upstream sequence, per species. We detected statistically significant enrichment of non-homologous human TISs co-occurring with human-specific TRs. On the contrary, homologous human TISs co-occurred significantly with non-human-specific TRs. 2991 human genes had at least one transcript, TIS of which was flanked by a human-specific TR. Text mining of a number of the identified genes, such as CACNA1A, EIF5AL1, FOXK1, GABRB2, MYH2, SLC6A8, and TTN, yielded predominant expression and functions in the human brain and/or skeletal muscle. CONCLUSION: We conclude that TRs ubiquitously flank and contribute to TIS selection at the trans-species level. Future functional analyses, such as a combination of genome editing strategies and in vitro protein synthesis may be employed to further investigate the impact of TRs on TIS selection.