Albà M Mar, Castresana Jose
Research Group on Biomedical Informatics, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Mol Biol Evol. 2005 Mar;22(3):598-606. doi: 10.1093/molbev/msi045. Epub 2004 Nov 10.
A large number of genes is shared by all living organisms, whereas many others are unique to some specific lineages, indicating their different times of origin. The availability of a growing number of eukaryotic genomes allows us to estimate which mammalian genes are novel genes and, approximately, when they arose. In this article, we classify human genes into four different age groups and estimate evolutionary rates in human and mouse orthologs. We show that older genes tend to evolve more slowly than newer ones; that is, proteins that arose earlier in evolution currently have a larger proportion of sites subjected to negative selection. Interestingly, this property is maintained when a fraction of the fastest-evolving genes is excluded or when only genes belonging to a given functional class are considered. One way to explain this relationship is by assuming that genes maintain their functional constraints along all their evolutionary history, but the nature of more recent evolutionary innovations is such that the functional constraints operating on them are increasingly weaker. Alternatively, our results would also be consistent with a scenario in which the functional constraints acting on a gene would not need to be constant through evolution. Instead, starting from weak functional constraints near the time of origin of a gene-as supported by mechanisms proposed for the origin of orphan genes-there would be a gradual increase in selective pressures with time, resulting in fewer accepted mutations in older versus more novel genes.
所有生物都共享大量基因，而许多其他基因则是某些特定谱系所特有的，这表明它们起源的时间不同。越来越多真核生物基因组的可得性使我们能够估计哪些哺乳动物基因是新基因，以及它们大致何时出现。在本文中，我们将人类基因分为四个不同的年龄组，并估计人类和小鼠直系同源基因的进化速率。我们发现，较古老的基因往往比较新的基因进化得更慢；也就是说，在进化过程中出现较早的蛋白质目前有更大比例的位点受到负选择。有趣的是，当排除一部分进化最快的基因或仅考虑属于给定功能类别的基因时，这种特性仍然存在。解释这种关系的一种方法是假设基因在其整个进化历史中都保持其功能限制，但最近进化创新的性质使得作用于它们的功能限制越来越弱。或者，我们的结果也与一种情况一致，即作用于基因的功能限制在进化过程中不必保持不变。相反，从基因起源时附近较弱的功能限制开始——正如为孤儿基因起源提出的机制所支持的那样——随着时间的推移，选择压力会逐渐增加，导致较古老基因与更新颖基因相比，接受的突变更少。
