Ohadi Mina, Tajeddin Nahid, Bayat Hadi, Annear Dale J, Maddi Ali M A, Khorshid Hamid R Khorram, Kavousi Kaveh, Delbari Ahmad, Nikkhah Alireza, Arabfard Masoud
Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
BMC Genomics. 2025 May 30;26(1):550. doi: 10.1186/s12864-025-11734-3.
Crossover and recombination create genetic diversity that reflects differences in the DNA sequences of different organisms. We previously reported that trinucleotide 2-repeat units (T2Us) are sites of crossover and consequent colonization, which are massively spread and shared across the genomes of human and several other primates. These sites underscore the preference for AT- over CG-rich sequences as recombination sites.
We extended our study to simpler repeat cores, consisting of AT/TA and CG/GC dinucleotides. An algorithm was designed to extract the genomic regions with a higher probability of recombination. To this end, we hypothesized that dinucleotide 3-repeat units (D3Us) are, at least in part, the basic overlapping units resulting from unequal crossover between dinucleotide 2-repeat units (D2Us). We mapped TATATA, ATATAT, CGCGCG, and GCGCGC across the human genome and analyzed their colonization (the distance between consecutive D3Us < 500 bp). We also studied several randomly selected colonies of diverse sizes in up to 100 vertebrate species using the UCSC and Ensembl Genome Browsers.
We found approximately four million AT/TA D3Us and one hundred thousand CG/GC D3Us across the human genome. The majority of these D3Us resided in colonies and spread ubiquitously along all chromosomes. AT/TA colonies were significantly larger and more intricate than CG/GC colonies. D2Us and D3Us were the primary sites of unequal crossover in these colonies, resulting in the emergence of primary recombinants (overlapping recombinants of D2Us/D3Us) and a vast repertoire of secondary recombinants (non-overlapping recombinants of D2Us/D3Us) and eventually, colonies of enormous intricacy and significance based on Poisson distribution. Intricacy was consistently detected across diverse colony sizes, from the smallest to the largest. The randomly selected colonies that were studied in other species were specific to or of their largest size in human.
We report ubiquitous and intricate colonies, in which D2Us and D3Us were the primary sites of crossover and recombination. It is plausible that minimal repeats such as D2Us, D3Us, and T2Us mark recombination as a ubiquitous rule across the human genome. This phenomenon is likely to transform our understanding of the magnitude, biological, and evolutionary outcomes of crossover and recombination.
交叉和重组创造了反映不同生物体DNA序列差异的遗传多样性。我们之前报道过，三核苷酸2重复单元（T2U）是交叉和随后定殖的位点，它们在人类和其他几种灵长类动物的基因组中大量分布并共享。这些位点强调了作为重组位点时对富含AT而非富含CG序列的偏好。
我们将研究扩展到由AT/TA和CG/GC二核苷酸组成的更简单的重复核心。设计了一种算法来提取具有较高重组概率的基因组区域。为此，我们假设二核苷酸3重复单元（D3U）至少部分是由二核苷酸2重复单元（D2U）之间不等交换产生的基本重叠单元。我们在人类基因组中定位了TATATA、ATATAT、CGCGCG和GCGCGC，并分析了它们的定殖情况（连续D3U之间的距离<500 bp）。我们还使用加州大学圣克鲁兹分校（UCSC）和Ensembl基因组浏览器研究了多达100种脊椎动物中几个随机选择的不同大小的群体。
我们在人类基因组中发现了约400万个AT/TA D3U和10万个CG/GC D3U。这些D3U中的大多数位于群体中，并沿所有染色体普遍分布。AT/TA群体比CG/GC群体明显更大且更复杂。D2U和D3U是这些群体中不等交换的主要位点，导致了初级重组体（D2U/D3U的重叠重组体）的出现以及大量二级重组体（D2U/D3U的非重叠重组体）的产生，最终基于泊松分布形成了极其复杂且具有重要意义的群体。在从最小到最大的各种群体大小中都持续检测到了复杂性。在其他物种中研究的随机选择的群体在人类中是特定的或最大的。
我们报告了普遍存在且复杂的群体，其中D2U和D3U是交叉和重组的主要位点。诸如D2U、D3U和T2U这样的最小重复序列作为贯穿人类基因组的普遍规则标记重组，这似乎是合理的。这种现象可能会改变我们对交叉和重组的规模、生物学及进化结果的理解。
