Table_2_Gene Size Matters: An Analysis of Gene Length in the Human Genome.xlsx

While it is expected for gene length to be associated with factors such as intron number and evolutionary conservation, we are yet to understand the connections between gene length and function in the human genome. In this study, we show that, as expected, there is a strong positive correlation between gene length, transcript length, and protein size as well as a correlation with the number of genetic variants and introns. Among tissue-specific genes, we find that the longest transcripts tend to be expressed in the blood vessels, nerves, thyroid, cervix uteri, and the brain, while the smallest transcripts tend to be expressed in the pancreas, skin, stomach, vagina, and testis. We report, as shown previously, that natural selection suppresses changes for genes with longer transcripts and promotes changes for genes with smaller transcripts. We also observe that genes with longer transcripts tend to have a higher number of co-expressed genes and protein-protein interactions, as well as more associated publications. In the functional analysis, we show that bigger transcripts are often associated with neuronal development, while smaller transcripts tend to play roles in skin development and in the immune system. Furthermore, pathways related to cancer, neurons, and heart diseases tend to have genes with longer transcripts, with smaller transcripts being present in pathways related to immune responses and neurodegenerative diseases. Based on our results, we hypothesize that longer genes tend to be associated with functions that are important in the early development stages, while smaller genes tend to play a role in functions that are important throughout the whole life, like the immune system, which requires fast responses.尽管基因长度已被证实与内含子数量、进化保守性等因素存在关联，但目前我们对人类基因组中基因长度与其功能之间的关联仍未完全阐明。本研究证实，正如预期所示，基因长度、转录本（transcript）长度与蛋白质长度之间存在显著正相关，同时基因长度也与遗传变异数量及内含子数量存在相关性。在组织特异性基因中，我们发现最长的转录本多在血管、神经、甲状腺、子宫颈及大脑中表达，而最短的转录本则多表达于胰腺、皮肤、胃、阴道与睾丸。正如此前研究所示，本研究发现自然选择会抑制长转录本基因的序列变异，同时促进短转录本基因的序列变异。此外我们还观察到，长转录本基因往往拥有更多的共表达基因、蛋白质-蛋白质相互作用（protein-protein interaction）关联以及更多的相关研究文献。在功能分析中，我们发现长转录本多与神经元发育相关，而短转录本则多参与皮肤发育及免疫系统功能调控。此外，与癌症、神经系统疾病及心脏疾病相关的通路多包含长转录本基因，而与免疫应答及神经退行性疾病相关的通路则多富集短转录本基因。基于上述研究结果，我们提出如下假说：长基因多与早期发育阶段的关键功能相关，而短基因则参与贯穿整个生命进程的核心功能，例如需要快速响应的免疫系统功能。