Human aging and somatic point mutations in mtDNA: a comparative study of generational differences (grandparents and grandchildren)

The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old) mutations (homoplasia and heteroplasmy). It is possible that both of these situations (homoplasia and heteroplasmy) were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life.

Genetical-demographic data from two amazonian populations composed of descendants of african slaves: Pacoval and Curiau

The Amazon region of Brazil includes communities founded by escaped slaves, some of which still remain relatively isolated. We studied two such Afro-Brazilian communities (Pacoval and Curiau), in the rural area of Alenquer, Pará, and in the metropolitan region of Macapá, Amapá, respectively. Among 12 blood loci, alleles considered as markers of African ancestry, such as HBB*S, HBB*C, TF*D1, HP*2M, ABO*B, RH*D-, and CA2*2 were found at frequencies that are expected for populations with a predominantly African origin. Estimates of interethnic admixture indicated that the degree of the African component in Curiau (74%) is higher than that of Pacoval (44%); an Amerindian contribution was not detected in Curiau. Estimated values of African ancestry fit well with the degree of isolation and mobility of the communities. Pacoval exhibited a high proportion of immigrants among the parents and grandparents of the individuals studied, whereas persons living in Curiau exhibited a low level of mobility, despite its location in the metropolitan area of Macapá city, suggesting a relatively strong barrier against the interethnic admixture in this population. In addition, analysis of genetic data in a sub-sample consisting of individuals whose parents and grandparents were born in the study site, and that probably represents the populations two generations ago, indicated that gene flow from non-black people is not a recent event in both populations.