The Proceedings of the Eighth International Conference on Creationism (2018)
becoming more and more unlikely. 9. Possible causes for variable mutation accumulation rates: The patterns we are seeing in human lineages display some strikingly similarities with the patterns seen in the famous LTEE bacterial experiment (Tenaillon et al. 2016). A single strain/culture of E. coli was separated into 12 isolated lineages and their genetic divergence over time was directly observed and documented. After 50,000 generations, two clones from each of the 12 lineages were sequenced. Six of the 12 lineages picked up an average of just 43.1 mutations over the 50,000 bacterial generations. But the other six lineages experienced hypermutation, ranging from 1100 to 2500 accumulated mutations. In exactly the same amount of time, the hypermutating strains accumulated two orders of magnitude more mutations than normal. There were two distinct patterns of mutation evident in the hypermutating strains (Table 3). Four of the cultures picked up a huge number of transitions of all four types, ranging from 115 to 1070 total mutations.Another two cultures picked up a huge number of A→C transversions (and obviously the reverse compliment T→G). The hypermutation in the famous citrate-digesting strain (Blount et al. 2008; Barrick and Lenski 2009) has been traced to a defective MutS gene. We suspect the there were similar mutations affecting DNA repair in the other hypermutating strains. Specific mutations to DNA repair systems can result in characteristic mutation accumulation patterns. We do not yet know if such patterns will be evident in the human genomic data. Preliminary analyses revealed interesting differences among the very rare African lineages, compared to all the other lineages, but this difference was not found to be statistically significant. This is an area for future research. Gene conversion (Trombetta and Cruciani 2017) is also a possible explanation for variable mutation rates. Rozen et al. (2003) estimated that an average of 600 nucleotides per newborn male have undergone gene conversion between the two arms of the Y chromosome, and Trombetta et al. (2014) concluded that gene conversion between similar portions of the X and Y chromosomes is frequent. Not only does the conversion rate vary by sex and age (Halldorsson et al. 2016), but it may depend on overall heterozygosity, if it is correlated to DNA excision and repair pathways during chromosomal recombination events (Duret and Galtier 2009). The African populations are much more heterozygous than non-Africans. For example, on chr22 the 504 individuals from the four African populations were heterozygous at 3.78% (+/- 0.20% SD) of all variable alleles. The 502 individuals from the five European populations were heterozygous at only 2.91% (+/- 0.15% SD) of all variable sites. However, to date it is unknown if conversion is truly associated with heterozygosity in humans. Alternatively, gene conversion is associated with rates of Carter et al. ◀ Y Chromosome Noah and mitochondrial Eve ▶ 2018 ICC 142 Mutator Status Clone Mutation Count Transitions Transversions AG GA CT TC AC AT CA CG GC GT TA TG Non-mutator Ara+2a 70 7 4 4 4 6 5 1 4 3 Ara+2b 70 7 5 4 4 6 5 1 4 3 Ara+4a 69 5 7 8 4 6 1 1 2 4 3 Ara+4b 69 5 7 8 4 6 1 1 2 4 3 Ara+5a 79 10 4 12 2 3 1 3 6 2 2 Ara+5b 81 10 4 11 2 4 1 2 5 2 3 Ara-5a 89 8 4 9 2 9 2 3 9 2 3 Ara-5b 94 9 3 10 3 9 2 2 9 2 4 Ara-6a 93 8 3 6 4 4 2 5 3 3 2 Ara-6b 77 8 3 8 1 5 2 4 1 4 1 2 Point-mutator Ara+6a 2595 10 5 6 3 1239 1 3 1 6 1311 Ara+6b 2335 8 3 5 1 1124 1 15 23 1 1136 Ara-1a 1112 7 2 6 4 511 2 17 24 2 506 Ara-1b 1135 8 2 7 4 521 2 16 25 2 516 Ara+3a 154 26 27 30 25 2 1 2 Ara+3b 156 30 23 28 31 3 1 1 2 Ara-2a 1056 220 203 180 225 4 4 3 1 1 1 6 4 Ara-2b 1117 210 232 213 255 4 6 3 3 2 3 1 Ara-3a 795 162 129 191 118 7 3 7 2 4 6 4 3 Ara-3b 822 183 135 177 116 7 3 11 4 4 11 5 2 Ara-4a 1343 245 290 234 265 3 4 4 8 6 4 3 1 Ara-4b 1362 248 290 238 262 6 4 4 8 6 4 4 2 IS mutator Ara+1a 125 11 4 4 7 3 4 1 5 2 8 Ara+1b 128 11 5 3 5 3 4 1 4 2 9 Table 3. Mutation accumulation patterns in the twelve cultures of the Long Term Evolution Experiment (LTEE). The mutation count incudes indels, inversions, mobile element insertions and losses, SNVs, etc. Hypermutating strains are shaded. Dark = the four transition-accumulating strains, including the “citrate-digesting” clone Ara-3. Light = two clones that have accumulated a considerable number of A→C, and its reverse compliment T→G, transversions.
Made with FlippingBook
RkJQdWJsaXNoZXIy MTM4ODY=