Prentout Djivan, Bykova Daria, Hoge Carla, Hooper Daniel M, McDiarmid Callum S, Wu Felix, Griffith Simon C, de Manuel Marc, Przeworski Molly
Department of Biological Sciences, Columbia University, New York, New York, United States of America.
Institute for Comparative Genomics and Richard Gilder Graduate School, American Museum of Natural History, New York, New York, United States of America.
PLoS Genet. 2025 Apr 15;21(4):e1011661. doi: 10.1371/journal.pgen.1011661. eCollection 2025 Apr.
Most of our understanding of the fundamental processes of mutation and recombination stems from a handful of disparate model organisms and pedigree studies of mammals, with little known about other vertebrates. To gain a broader comparative perspective, we focused on the zebra finch (Taeniopygia castanotis), which, like other birds, differs from mammals in its karyotype (which includes many micro-chromosomes), in the mechanism by which recombination is directed to the genome, and in aspects of ontogenesis. We collected genome sequences from three generation pedigrees that provide information about 80 meioses, inferring 202 single-point de novo mutations, 1,088 crossovers, and 275 non-crossovers. On that basis, we estimated a sex-averaged mutation rate of 5.0 × 10-9 per base pair per generation, on par with mammals that have a similar generation time (2-3 years). Also as in mammals, we found a paternal germline mutation bias at later stages of gametogenesis (of 1.7:1) but no discernible difference between sexes in early development. Examining recombination patterns, we found that the sex-averaged crossover rate on macro-chromosomes is 0.93 cM/Mb, with a pronounced enrichment of crossovers near telomeres. In contrast, non-crossover rates are more uniformly distributed. On micro-chromosomes, sex-averaged crossover rates are substantially higher (3.96 cM/Mb), in accordance with crossover homeostasis, and both crossover and non-crossover events are more uniformly distributed. At a finer scale, recombination events overlap CpG islands more often than expected by chance, as expected in the absence of PRDM9. Estimates of the degree of GC-biased gene conversion (59%), the mean non-crossover conversion tract length (32 bp), and the non-crossover-to-crossover ratio (5.4:1) are all comparable to those reported in primates and mice. Therefore, properties of germline mutation and recombination resolutions remain similar over large phylogenetic distances.
我们对突变和重组基本过程的大部分理解都源于少数几种不同的模式生物以及对哺乳动物的系谱研究，而对其他脊椎动物的了解甚少。为了获得更广泛的比较视角，我们聚焦于斑胸草雀（Taeniopygia castanotis），它与其他鸟类一样，在核型（包括许多微小染色体）、重组导向基因组的机制以及个体发育方面与哺乳动物不同。我们从三代系谱中收集了基因组序列，这些系谱提供了约80次减数分裂的信息，推断出202个单点新生突变、1088次交叉和275次非交叉。在此基础上，我们估计每代每个碱基对的性别平均突变率为5.0×10⁻⁹，与具有相似世代时间（约2 - 3年）的哺乳动物相当。同样与哺乳动物一样，我们发现在配子发生后期父系生殖系存在突变偏差（比例为1.7:1），但在早期发育阶段两性之间没有明显差异。检查重组模式时，我们发现常染色体上的性别平均交叉率为0.93 cM/Mb，端粒附近交叉明显富集。相比之下，非交叉率分布更均匀。在微小染色体上，性别平均交叉率显著更高（3.96 cM/Mb），符合交叉稳态，并且交叉和非交叉事件分布更均匀。在更精细的尺度上，重组事件比随机预期更频繁地与CpG岛重叠，这在没有PRDM9的情况下是预期的。GC偏向基因转换程度（59%）、平均非交叉转换片段长度（约32 bp）以及非交叉与交叉比率（5.4:1）的估计值都与灵长类动物和小鼠的报告值相当。因此，生殖系突变和重组分辨率的特性在较大的系统发育距离上仍然相似。
