PCB4522 Molecular Genetics

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PCB4522 Molecular Genetics Spring semester
2007 First Period (Yikes!)
Announcement part-time dishwasher position
available in the Medical School 10hr/wk at
8.00/hr. Contact Dr. Marie Becker email
mnbecker_at_ufl.edu.
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PCB4522 Spring 20067
Exam lectures date Exam 1 6 Jan 26 16.68
M. L. King Day Jan 15-no class Exam
2 10 Feb 21 27.77 Spring
Break Mar 10-17 no class Exam 3 10 Mar
26 27.77 Exam 4 10 Apr 20 27.78 Cumulative 36 M
ay 1 1230-230 pm Genome project 2 pts
added to final grade
100.00
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The History of Man is written in DNA.
Just hanging out. No jobs tools had not been
invented.
Australopithecine
Nicholas Wade (2006) Before the Dawn. Penguin
Press, New York pp. 312.
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Tool making advanced in stages corresponding to
large scale changes in genetic makeup.
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Chrome magnum
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The was populated by archaic humans until 60,000
yrs ago.
Brain size gradually increased

• 500,000 yrs ago brain size increased
  significantly.
• 200,000 yrs ago it reached modern levels.

Archaic humans

• Homo erectus (Asia)
• Homo neanderthalis (Europe/Middle East)

Three human species 50,000 yrs ago.
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The second exit from Africa was 50,000 yrs ago.

• Ocean levels were 200 ft. lower than today due
  to glaciation.

• Genetic evidence indicates that a bottleneck
  occurred reducing the population of modern humans
  to around 5,000 persons.
• Only 150 of these managed to break out of Africa
  in a single exodus.
• Modern humans reached Australia about 40,000 yrs
  ago.

The southern route to Sahul
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Highly branched tree evidence of rapid increase
in population size.
Y-chromosome
Mitochondria
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Remnant populations of the ancestral population
of 5,000
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There seems to have been a series of mutations in
the brain that gave ancestors of modern humans an
edge over the archaic humans that blocked the
exits out of Africa These resulted in the
capacity for highly developed language. The story
of FOXP2.
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Archeologists believe that the appearance of art
correlates with the development of complex
language.
FOXP2 phenotype?
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Brain of the bonobo (related to chimps) overlaid
onto the human brain red and yellow areas had to
be stretched, blue areas are same size. Brocas
area is one of those in red.
Language area (Brocas and Wemickes) in
yellowoverlap (orange) with areas critical for
imitations (red).
Anatomically modern humans since about 300,000
yrs ago.
Chimps gesture with both face and hands
Holden (2004) The origin of speech. Sci.
3031316-1319.
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FoxP2 transcription factor
The FoxP2 gene has 715 amino acids. The
comparisons of nonsynonymous and synonymous
nucleotide substitutions indicate that these
mutations have been highly selected within the
last 100,000-200,000 yrs.
Some believe that these two recent mutations in
FOXP2 enabled the ancestral human population to
possess the genetic edge to successfully break
out of Africa 50,000 yrs ago.
The FOXP2 gene is ancient in origin and highly
conserved. Chimpanzees and gorillas carry the
identical version which must be the same one
carried by the common ancestor to Chimps and
humans 5 million yrs ago. The Chimp/gorilla
version only differs by a single amino acid from
that present in mice. In the 65 million yrs
separating chimps and mice, there was only a
single mutation however, in the 5 million yrs
since humans split from chimps, two mutations
have occurred.
Zhang, Webb and Podlaha (2002) Accelerated
Protein Evolution and Origins of Human-Specific
Features FOXP2 an exmple. Genetics 162
1825-1835.
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Synonymous Mutations no change in the amino acid
residue encoded in the protein neutral
molecular clock. Nonsynonymous Mutations change
the amino acid. Ratio of nonsynonymous to
synonymous mutations gives indication of
selection pressure. Number of synonymous
mutations within a population gives a measure of
the time elapsed molecular clock.
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FoxP2 transcription factor
Zhang, Webb and Podlaha (2002) Accelerated
Protein Evolution and Origins of Human-Specific
Features FOXP2 an exmple. Genetics 162
1825-1835.
Mutations at sites 303 and 325 distinguish humans
from other primates.
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FoxP2 transcription factor
Mutations at R553H cause verbal dyspraxia, which
affects articulation of language more than
comprehension, and high speed movements of the
vocal organs required for intelligible speech.
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FoxP2 transcription factor
Arginine 553 is a part of helix 3 which is
involved in DNA recognition. R553H mutants do not
recognize the consensus DNA element in the
promoter, and also are deficient in nuclear
localization.
Stroud et al. (2006) Structure of the Forkhead
Domain of FOXP2 bound to DNA. Structure 14
159-166.
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Evolution continues to change us.
Lactose tolerance has arisen several times in the
last 10,000 yrs. The best documented is that
corresponding with the breeding of the milk cow
in North Central Europe from 6,500-5,000 yrs ago
associated with the Funnel Beaker culture.
Peja-Pereira et al. (2003) Gene-culture
coevolution between cattle milk protein genes and
human lactase genes. Nature Gen. 35 311-312.
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Mans Journey out of Africa http//www.bradshawfou
ndation.com/journey/ Origins of Modern
Humans Multiregional or Out of Africa?By
Donald Johanson http//www.actionbioscience.org/ev
olution/johanson.html