Human mitochondrial molecular clock

Because of the uncertainties from the archeological record, scientists have turned to molecular dating techniques in order to refine the timeline of human evolution.

A major goal of scientists in the field is to develop an accurate hominid mitochondrial molecular clock which could then be used to confidently date events that occurred during the course of human evolution.

Current research has been focused on resolving the high variability obtained from different rate estimates.

Since the emergence of the species homo sapiens about 200,000 years ago, the human population has expanded from a few thousand individuals living in Africa to over 8 billion worldwide.

For this reason, some studies avoid coding region or nonsynonymous mutations when calibrating the molecular clock.

The mutation rate is also thought to be faster in recent times, since the beginning of the Holocene 11,000 years ago.

[3][5] Phylogeny based methods are estimated by first reconstructing the haplotype of the most recent common ancestor (MRCA) of a sample of two or more genetic lineages.

A requirement is that the time to the most recent common ancestor (TMRCA) of the sample of lineages must already be known from other independent sources, usually the archeological record.

According to Henn et al. 2009, phylogeny based methods take into account events that occur over long time scales and are thus less affected by stochastic fluctuations.

Anatomically modern humans (AMH) spread out of Africa and over a large area of Eurasia and left artifacts along the northern coast of the Southwest, South, Southeast and East Asia.

Cann, Stoneking & Wilson (1987) did not rely on a predicted TCHLCA to estimate single-nucleotide polymorphism (SNP) rates.

In addition they used RFLP technology (Restriction fragment length polymorphism) to examine differences between DNA.

The chimp-human last common ancestor (CHLCA) is frequently applied as an anchor for mt-TMRCA studies with ranges between 4 and 13 million years cited in the literature.

The other weakness is the non-clocklike accumulation of SNPs, would tend to make more recent branches look older than they actually are.

However, the oldest archaeological sites that also demonstrate anatomically modern humans (AMH) are in China and Australia, greater than 42,000 years in age.

Given that the mitogenome is about 16553 base pairs in length (each base-pair which can be aligned with known references is called a site),[8] the formula is: The '2' in the denominator is derived from the 2 lineages, human and chimpanzee, that split from the CHLCA.

[9] Because the TCHLCA is subject to change with more paleontological information, the equation described above allows the comparison of TMRCA from different studies.

To overcome the effects of saturation, HVR analysis relied on the transversional distance between humans and chimpanzees.

[10] A transition to transversion ratio was applied to this distance to estimate sequence divergence in the HVR between chimpanzees and humans, and divided by an assumed TCHLCA of 4 to 6 million years.

As noted in the table above, the rate of evolution is so high that site saturation occurs in direct chimpanzee and human comparisons.

Comparing chimp and human mitogenomes, they noted 26.4 transversions within the HVR regions, however they made no correction for saturation.

The estimated sequence divergence 0.738/site (includes transversions) is significantly lower than the ~2.5 per site suggested by Soares et al. (2009).

[13] The problem with mutations in the coding region has been described as such: mutations occurring in the coding region that are not lethal to the mitochondria can persist but are negatively selective to the host; over a few generations these will persist, but over thousands of generations these slowly are pruned from the population, leaving SNPs.

The problem with rare mutations in the human mitogenomes is significant enough to prompt a half-dozen recent studies on the matter.

Ingman et al. (2000) estimated the non-D loop region evolution 1.7 × 10−8 per year per site based on 53 non-identical genomic sequence overrepresenting Africa in a global sample.

Lack of historical perspective might explain the second issue, the problem of rate variation is something that could only be resolved by the massive study of mitochondria that followed.

HVR is exceptionally prone to saturation, leading to the underestimation of the SNP rate when comparing very distantly related lineages