Mutation Rate
由于生物基础薄弱，一些单位（关于mutation rate）就把我搞乱了，咳咳故作镇定。
…a nucleotide substitution rate of
per site per year both in poultry and in House Finches, an exceptionally fast rate rivaling some of the highest estimates reported…
Mutation Rate (SNP/Nucleotide/Replication) (Barrick and Lenski, 2013)
1.substitution rate of…per site per year: SNP/Nucleotide/Year
2.SNP/Nucleotide/Year * yy Year = SNP/Nucleotide
3.SNP/Nucleotide / rr Replication = SNP/Nucleotide/Replication
4.SNP/Nucleotide/Replication: number of mutations per base pair for each replication event
5.SNP/Nucleotide/Replication=mutations/bp/replication
清楚了！
Average rates of mutation: what we want is measurements of the number of mutations per base pair for each replication event.
how is the mutation rate measured?
The genomic era has ushered in the ability to read out mutation rates directly. (迎来了直接测量mutation rate的世纪)
older methods of inference: based on indirect evolutionary comparisons or studies of mutations that are visually remarkable such as those resulting in color changes of an organism or changes in pathogenic outcomes.
query the genome directly through sequencing at different time points in the evolutionary process and to examine both
- where these mutations occur
- how they accumulate with time
| organism | mutations/bp/replication | mutations/bp/generation |
|---|---|---|
| human H.sapiens |
Some calculation
- Back of the envelope calculation of the mutations in an overnight culture of bacteria. One finds that every possible base pair change in explored
…overnight culture…
during the final doubling there are ~
所以说
Note: the value of the mutation rate is on a per generation basis and is thus the accumulation in the gametes of mutations occurring over several tens of genome replications between fertilization of the egg all the way until the formation of the next generation of gametes.
gametes: 配子（形成受精卵的精子或卵子）
fertilized egg: 受精卵
- How many chromosome replications occur per generation?
In humans it is estimated that there are about 20-30 genome replications between the fertilized egg and the female gametes (BNID 105585) and about ten times that for males, with large variation depending on age (BNID 105574).
啊男性的replication是女性的10倍，是因为男性精子比较多？怂x 好像不太对啊……这样200-300 genome replications显然不止啊，那不是以亿计的么，害不清楚……可能是男性新陈代谢更旺盛吧。。*乱讲的
Suppose
a gap: Though we discuss mutations on a per replication or per generation rate, non-dividing cells will also have damage caused to their genomes through mechanisms such as radiation and reactive oxygen species. When the damage is corrected, mutations accumulate with time at rates that are still not well constrained experimentally.
Note that there are many different classes of point mutations that can be categorized as a result of such sequencing experiments, giving a picture of whether the mutations are synonymous or non-synonymous and whether the mutation event is a transition or transversion.
Different mutations are not evenly distributed. They are dominated by a G-C base pair being transformed into an A-T based pair. This arises due to the biochemical susceptibility of the nucleotides to being mutated.
Another common type of mutation in the genome are insertion and deletion events, so called indels. Other forms of genome rearrangement such as the “jumping genes”.
后面这个我（非生物学生）看着挺神奇的
- Back of the envelope calculation of the number of mutations throughout humanity per generation. We find that each single base pair mutation is explored dozens of times in every generation but that a specific combination of two base pairs will require an unrealistic number of generations to occur at random. A fitness advantage or some contingency mechanism is required to achieve these concerted changes.
下面这个计算说明不同人之间其实都有差异，而且每一个位点的突变都被全球人民fully explored…难道不是有点神奇吗？事实上好像不是这样？我觉得？人类基因组不是差别不大的吗？
地球上人口假设7 billion，那么我们前面算过每个generation单个genome会发生
这样的话，
而对于人类每一个genome，有
下面这个计算说明人类能进化到今天，其实相当不容易吗？或者说每一个基因序列都是很难得的。。
越来越希望这博客就自己看看了，文风奇特……