Data from: Construction of ultra-dense linkage maps with Lep-MAP2: stickleback F2 recombinant crosses as an example

High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium and chromosomal rearrangements across chromosomes, sexes and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identify errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultra-dense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (~6 markers/cM) linkage maps containing 18 691 and 20 054 SNPs. The two maps showed a high degree of synteny, but female maps were 1.5 to 2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (<5%) of interchromosomal re-arrangements. However, a fairly large (ca. 10Mb) translocation from autosome to sex chromosome was detected in both maps. These results illustrate the utility and novel features of Lep-MAP2 in assembling high-density linkage maps, and their usefulness in revealing evolutionarily interesting properties of genomes, such as strong genome-wide sex-bias in recombination rates.

高密度连锁图谱是基因组生物学与进化遗传学领域的重要研究工具，可量化不同染色体、性别及种群间的重组、连锁不平衡与染色体重排程度。其是验证与优化从头基因组组装（de novo genome assembly）的最优手段之一，且随着标记密度提升，识别组装错误的能力也会同步增强。但受限于现有软件的技术瓶颈，高密度连锁图谱的构建仍存在不小挑战。本文介绍Lep-MAP2——一款用于构建超高密度全基因组连锁图谱的专用软件。该软件可兼容多种家系结构，并可通过考虑无交叉减数分裂（achiasmatic meiosis）来进一步提升连锁图谱的构建精度。模拟实验结果表明，Lep-MAP2在计算效率与构建精度上均优于现有其他图谱构建软件。当将其应用于两个九刺鱼（Pungitius pungitius）种群间的大型F2代重组杂交群体时，该软件成功构建得到两张高密度（约6个标记/厘摩）连锁图谱，分别包含18691和20054个单核苷酸多态性（Single Nucleotide Polymorphism，简称SNP）位点。两张图谱均表现出极高的共线性（synteny），但所有连锁群的雌性图谱长度均为雄性图谱的1.5至2倍，这表明雄性个体存在全基因组水平的重组抑制现象。通过与三刺鱼（Gasterosteus aculeatus）的基因组序列进行比对，发现二者存在极高的种间共线性，染色体间重排的发生频率极低（<5%）。但两张图谱均检测到一段较大的（约10Mb）常染色体向性染色体的易位片段。上述结果既充分展示了Lep-MAP2在构建高密度连锁图谱中的实用性与创新特性，也证实了该工具在揭示基因组进化相关的关键特征——比如全基因组水平上显著的重组速率性别偏倚——方面的重要应用价值。