Abstract
A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (approximate to 11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

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In this paper we briefly present our feelings about urban logistic and its role in urban mobility. In some way, we can say that this is a position paper based on an extensive review of all known related published material. We support the development of new approaches for the management of passenger and freight transport together as a single logistics system; based on the access to more and more sophisticated flows of data and better communication means, we envisage the dissemination of sufficient information for the correct decision of every citizens between several mobility options in real time (especially with the support of mobile technology); and we sustain that new tools are needed to help the design of innovative business models and policies, and the change of habits and behaviors. We visualize urban logistics as a multi-stakeholder, multi-criteria and multimodal mobility dynamic system.

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