Chicken domestication: an updated perspective based on mitochondrial genomes.

Domestic chickens (Gallus gallus domesticus) fulfill various roles ranging from food and entertainment to religion and ornamentation. To survey its genetic diversity and trace the history of domestication, we investigated a total of 4938 mitochondrial DNA (mtDNA) fragments including 2843 previously published and 2095 de novo units from 2044 domestic chickens and 51 red junglefowl (Gallus gallus). To obtain the highest possible level of molecular resolution, 50 representative samples were further selected for total mtDNA genome sequencing. A fine-gained mtDNA phylogeny was investigated by defining haplogroups A-I and W-Z. Common haplogroups A-G were shared by domestic chickens and red junglefowl. Rare haplogroups H-I and W-Z were specific to domestic chickens and red junglefowl, respectively. We re-evaluated the global mtDNA profiles of chickens. The geographic distribution for each of major haplogroups was examined. Our results revealed new complexities of history in chicken domestication because in the phylogeny lineages from the red junglefowl were mingled with those of the domestic chickens. Several local domestication events in South Asia, Southwest China and Southeast Asia were identified. The assessment of chicken mtDNA data also facilitated our understanding about the Austronesian settlement in the Pacific.

Pseudomitochondrial genome haunts disease studies.

The accidental amplification of nuclear mitochondrial pseudogenes (NUMTs) can pose a serious problem for mitochondrial disease studies. This report shows that the mutation spectrum left by spurious amplification of a NUMT can be detected because it usually differs considerably from the authentic natural spectrum. This study examined the problem introduced by an ND5 gene NUMT that was recorded in a proband with hearing loss and reviews other disease studies erroneously reporting NUMT variation as genuine mutations in their patients. NUMTs can emerge in population genetic studies, as exemplified here by cases in this study and from published sources. Appropriate database searches and a phylogenetic approach can prevent hasty claims for novelty of mitochondrial DNA (mtDNA) variants inadvertently derived from NUMTs and help to direct investigators to the real source.

Polymorphisms in the C-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (SARS-CoV) infection.

BACKGROUND: Polymorphisms of CLEC4M have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (SARS-CoV). DC-SIGNR, a C-type lectin encoded by CLEC4M, is a receptor for the virus. A variable number tandem repeat (VNTR) polymorphism in its neck region was recently associated with susceptibility to SARS infection. However, this association was controversial and was not supported by subsequent studies. Two explanations may account for this discrepancy: (1) there may be an unknown predisposition polymorphism located in the proximity which is linked to the VNTR; or (2) it was a spurious association due to unrecognised population structure in the VNTR. METHODS: We performed a comprehensively genetic association study on this C-type lectin gene cluster (FCER2, CLEC4G, CD209, and CLEC4M) at 19p13.3 by a tagging single nucleotide polymorphisms (SNPs) approach. RESULTS: 23 tagSNPs were genotyped in 181 SARS patients and 172 population controls. No significant association with disease predisposition was detected. Genetic variations in this cluster also did not predict disease prognosis. However, we detected a population stratification of the VNTR alleles in a sample of 1145 Han Chinese collected from different parts of China. CONCLUSION: The results indicated that the genetic predisposition allele was not found in this lectin gene cluster and population stratification might cause the previous positive association.

More evidence for non-maternal inheritance of mitochondrial DNA?

BACKGROUND: A single case of paternal co-transmission of mitochondrial DNA (mtDNA) in humans has been reported so far. OBJECTIVE: To find potential instances of non-maternal inheritance of mtDNA. METHODS: Published medical case studies (of single patients) were searched for irregular mtDNA patterns by comparing the given haplotype information for different clones or tissues with the worldwide mtDNA database as known to date-a method that has proved robust and reliable for the detection of flawed mtDNA sequence data. RESULTS: More than 20 studies were found reporting clear cut instances with mtDNAs of different ancestries in single individuals. As examples, cases are reviewed from recent published reports which, at face value, may be taken as evidence for paternal inheritance of mtDNA or recombination. CONCLUSIONS: Multiple types (or recombinant types) of quite dissimilar mitochondrial DNA from different parts of the known mtDNA phylogeny are often reported in single individuals. From re-analyses and corrigenda of forensic mtDNA data, it is apparent that the phenomenon of mixed or mosaic mtDNA can be ascribed solely to contamination and sample mix up.

[Mitochondrial DNA sequence variations of Shui ethnic group].

The mtDNA hypervariable segment I sequences (HVS I) were sequenced in 64 Shuis from Guizhou Province. 73 sites were polymorphic in the 495 bp fragment that sequenced, identified 48 different haplotypes. Phylogenetic analysis of the haplotypes suggested that there were some ancestral haplotypes in current Shuis, and these haplotypes were also present in Eurasia populations as well as in other ethnic groups. Demographic analysis of the Shuis demonstrated a unimodal distribution that is typical for a population undergone expansion in the past and with a high Tau value, which suggested that the Shui group might be a ancestral population. Combined with the analysis of the reported data, the Shui ethnic group showed a generally similar genetic component with the Zhuang from Guangxi, but it is also different from these typical south populations as Zhuang, Cantonese.

Evaluating the susceptibility of mitochondrial DNA germline mutations in Chinese cancer patients.

It has been suggested that impairment of mitochondrial oxidative phosphorylation (OXPHOS) is a common character in cancer cells, urging attention to variation on mitochondrial DNA (mtDNA) that encodes 13 units of the OXPHOS. However, most of mtDNA somatic mutations in cancer were suggested to result from the relaxed functional constrains and thus the byproducts of tumorigenesis. MtDNA germline mutations present not only in the cancer tissue but also in the normal tissue. However, it remains unclear whether the cancerous mtDNA germline mutations suffered similar selective constraints as the somatic mutations did. To address this question, we collected 153 whole mitochondrial genomes (including 20 newly obtained genomes in this study) from the normal tissues of cancer patients and compared with a number of 561 whole mtDNA sequences from the general population in China. Different from the observations on cancerous mtDNA somatic mutations, our results revealed that the germline mutations showed no significant difference between the cancer patients and the general population in either the sub-haplogroup composition, mutation pattern or the potential pathogenicity of the private mutations. It then seems that regulation on cellular OXPHOS level, triggered by mtDNA variation to some extent, exerts little influence on the susceptibility of cancer, which echoes the opinion that aerobic glycolysis, not mitochondrial respiration, plays the key role in generating energy in cancer cells, thus suggesting the role of most mtDNA mutations in cancer likely being overestimated.

Reappraising the relationship between mitochondrial DNA variant m.16189T>C and type 2 diabetes mellitus in East Asian populations.

The role of mitochondrial DNA (mtDNA) variant 16189T>C in type 2 diabetes mellitus (T2DM) remains hotly debated in the past decade. If mutation 16189T>C indeed posed a risk to T2DM, as echoed by some recent studies, correlation between this mutation and disease should be observed when carrying out a systematical study using data and samples collected in a large geographic region in China. To test this hypothesis, we first performed a linear regression analysis between the prevalence of T2DM and the allele frequency of 16189C variant in 10 East Asian populations, and further genotyped this variant in two casecontrol cohorts from west Han Chinese (Kunming and Xining). Linear regression analysis showed that no significant correlation was observed (r(2)=0.211, P=0.181), and the genotyping results indicated that the m.16189T>C frequency difference between case and control was not significant in either populations (P=0.38 and 0.89 for Kunming and Xining, respectively). Matrilineal backgrounds constitution (in terms of haplogroups) analysis generated a similar haplogroup distribution in both populations (P>0.1). All results failed to substantiate that m.16189T>C may play an active role in the development of T2DM in East Asian populations.

Identification of Native American founder mtDNAs through the analysis of complete mtDNA sequences: some caveats.

In this study, a detailed analysis of both previously published and new data was performed to determine whether complete, or almost complete, mtDNA sequences can resolve the long-debated issue of which Asian mtDNAs were founder sequences for the Native American mtDNA pool. Unfortunately, we now know that coding region data and their analysis are not without problems. To obtain and report reasonably correct sequences does not seem to be a trivial task, and to discriminate between Asian and Native American mtDNA ancestries may be more complex than previously believed. It is essential to take into account the effects of mutational hot spots in both the control and coding regions, so that the number of apparent Native American mtDNA founder sequences is not erroneously inflated. As we report here, a careful analysis of all available data indicates that there is very little evidence that more than five founder mtDNA sequences entered Beringia before the Last Glacial Maximum and left their traces in the current Native American mtDNA pool.