Łukasz Olczak , Silesian University of Technology

1. A project on alignment of short tandem repeat loci between Homo Sapiens and Homo Neanderthalensis genomes ŁukaszOlczak, Silesian University of Technology RafałPokrzywa, Silesian University of Technology Krzysztof Cyran, Silesian University of Technology AndrzejPolański, Silesian University of Technology

2. Aim: • Align STR loci between human and neanderthal , and verify implications on: • Mechanisms of STR evolution • Quality of Neanderthal DNA assembly • Demographic scenarios between Homo Sapiens and Homo Neanderthalensis

3. Methods 1/3 • BWtrs – Burrows-Wheeler transform based tool for searching tandem repeats in O(n log n) “BWtrs: A tool for searching for tandem repeats in DNA sequences based on the Burrows-Wheeler transform.” R. Pokrzywa, A. Polański Genomics 2010 • We found:

4. Methods 2/3 • STR alignment technique – extension of Needleman-Wunch algorithm • Scoring function of aligned pair of tandem repeats – 1 – if STR motif of pair is the same and there is high similarity between aligned flanking sequences 0 - otherwise • Example:

5. Dot plot (chr22)

6. Optimal path (chr22)

7. Methods 3/3 • Mutability measure: • Average squared divergence between binned orthologous – with correction for detecting threshold • Affected by both mutation rate and variance in mutation step size

8. Results 1/5

9. Results 2/5

10. Results 3/5

11. Results 4/5 • We use regression model to explain variability in microsatellite mutability • Predictors: • Motif size • No. repeats • Length in bp • R2=0.72, p=3E-10

12. R2=0.71,p=4.15E-11

13. Conclusions • 72% variation of mutability is explained by these 3 predictors • There is a positive correlation between STR length, repeat number and mutability • Motif size has negative effect on mutability • The strongest predictor is microsatellite length in bp, next is motif size. • Number of repeats has much more weaker influence on STRs mutability than length in bp

14. Conclusions • We assumed generation time 20 years and divergence time between human and Neandertal825000 y.a. • Our estimates of microsatellite mutation are significantly lesser than estimates obtained for human-chimp alignment • The more likely time of divergence is 500000 y.a. which is consistent with mitochondrial studies

15. Conclusions • Neanderthal dinucleotide microsatellite lengths are significantly longer than their orthologous in human • There are observations that microsatellite mutation rates are higher in population with higher fraction of heterozygotes • This results confirms that in human history occurred a population bottleneck (70,000 y. a.) followed by exponential growth

16. Conclusions • The quality of assembly of the Neanderthal’s nuclear DNA is very low, which caused by damage of ancient DNA • There is tendency to assembly shorter STRs.

17. Thank you for your attention!!