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Notas:
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Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering
the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of
cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and
whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out
an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we
examined whether genes with positively selected promoters (Prom+ genes) show systemic differences with respect to a set
of genes with positively selected protein-coding regions (Cod+ genes). We found that the number of genes in each set was
not significantly different (8.1% and 8.5%, respectively). Furthermore, a functional analysis showed that, in both cases,
positive selection affects almost all biological processes and only a few genes of each group are located in enriched
categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function.
On the other hand, we show that the topology of the human protein network has a different influence on the molecular
evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when
compared with a reference distribution (P = 0.008, for Eigenvalue centrality). Moreover, the frequency of Prom+ genes
increases from the periphery to the center of the protein network (P = 0.02, for the logistic regression coefficient). This
means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions,
and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in
the periphery. These results show that proximal promoters have had a systemic contribution to human evolution by
increasing the participation of central genes in the evolutionary process. |
